Considering the Outer Limits of Organ Bioprinting

The technology to print organs from raw materials - the patient's own cells, scaffolding material, and so forth - is in its earliest stages. There is some hope that this field could help to extend healthy human life by offering on-demand replacements for failing and age-damaged tissue. To date a few soft tissues, blood vessel-like structures, and bone have been successfully printed. There have been some important advances in using the self-assembly properties of living cells to do some of the work instead of the printer. The first replacement printed organs are probably more than a decade out, but there is a great deal more that could be accomplished beyond that goal.

When looked at over the long term, a broad category of modern technology might have a life cycle in the region of five decades or so. It moves from first experimental designs to mature uses in a few fields to a comprehensive portfolio of sophisticated uses in many fields over this fifty year span, and then its use declines as a new and better technology emerges. Definitions and time frames can be argued either way, but fifty years is a good round number that matches up with the life span of a number of 20th century technologies.

What can we envisage for the fifty year anniversary of bioprinting, in 2060, give or take a few years? What are the outer limits of the possible and the plausible? One starting point is the known conflict between young tissue and age-damaged systems in the body. Cells take their cues from the environment, and in some cases the environment has become actively hostile. Consider, for example, the death of motor neurons in Parkinson's disease: replacement cells may buy only a little time before they succumb to the same environmental issue that killed their predecessors. Also, we might think of muscle tissue that declines because stem cell populations in the old are instructed by their environment to perform less maintenance.

There are many whole-body, multi-organ, or regional biochemical feedback and control loops in the body. There are types of age-related damage that involve the intracellular accumulation of biochemical junk - simply replacing cells doesn't get rid of that. If your only tool is bioprinting (which won't be the case, but let us think inside the box for a while here), then the solution to these problems starts to look like replacing more of the body at one time. How much of the body could be replaced at once? Based on what is known today, everything except for the brain.

So one might consider a future bioprinting scenario in which an old body is completely discarded, the brain removed and placed within a printing vat. This machine would be something like an enclosed person-sized nutrient bath surrounded by interconnected machinery, feeds, bioreactors, and thousands of small manipulator arms and hair-fine printer heads. All controlled by sophisticated software and observed by medical technicians. There the patient would remain under sedation for however many months it required to print and assemble all the components of a new body. This would require a vastly greater knowledge of nerve regrowth than exists today, given that the brain would have to be reconnected to this body, but most of the remaining issues seem to be mechanical ones: how to assemble a bioprinted body (do you print it all at once in situ, or in pieces which you then move into place and print around?), how and when to connect vascular systems, and so forth.

The one thing you're left with at the end of the day is that this would be an old brain in a young body. Many of metabolism's controlling systems involve the brain, and an old brain has an age-damaged vascular system, vulnerable to surges in blood pressure. You can probably think of other biological mismatches that might cause disaster for an old brain hooked up to a vigorous young body. But these are problems that can be solved.

That said, I don't think the scenario I've painted above is plausible. It's feasible, but I strongly suspect that other branches of medical technology will make it obsolete before it becomes practical. 2060 is a world and a half away: we're expecting to see transformative medical nanomachinery emerge into widespread use by the 2040s, for example. For my money, a much more likely state of rejuvenation technology for baseline human biology in 2060 is the Strategies for Engineered Negligible Senescence vision: an array of therapies (or nanorobotic implementations) that remove biochemical damage in situ. Vaccines or artificial immune cells to clean out the buildup of unwanted biochemicals, replacing mitochondrial DNA or the mitochondria themselves wholesale, targeted destruction of senescent cells, swapping in new stem cell populations to repair everything else, that sort of thing. This would be less a case of tearing down the house to build a new one and much more a case of ongoing, period renovation.

The Campaign Against Aging

The Campaign Against Aging is a new grassroots advocacy initiative for longevity science of the SENS variety, announced a few days ago. I'm always pleased to see folk motivated and rising to the challenge: "Aging kills 100,000 out of the 150,000 people that die each day worldwide and inflicts an enormous amount of suffering. No other problem facing humanity can equal this tragedy. ... Aging is caused by the accumulation of damage in the human body that leads to age-related disease and eventually death. Medical therapies designed to remove this damage could restore the body to a youthful state. ... While most organizations focus on slowing down the aging process, more daring organizations seek to develop therapies that could reverse aging itself. Unfortunately, progress against aging has been slow due to lack of funding." The more groups that work to spread this message and raise funds for research, the better. Diversity is one of the keys to success in any endeavor - a greater variety in methods means a larger chance of at least one attempt succeeding.


Present Activities at the Methuselah Foundation

From the Methuselah Foundation Blog: "As the decade draws to a close, I'm looking ahead to the next one. And the next. I am optimistic that my chance of living a long, healthy life get better every day. I see the possibility of adding happy, healthy, productive years to my life and yours. No cancer, no Alzheimer's and a heart that keeps on beating. Wouldn't we all want an extra decade to spend with your family, to accomplish our goals and to enjoy life. Methuselah Foundation is working on it! We have three initiatives underway right now as we wrap up the decade and begin a new one. ... In 2009 we awarded a special Mprize for a study that showed unequivocally that mice lived longer when they took the drug rapamycin. We believe in the power of prizes. We created the Mprize to encourage, incentivize and reward world-class scientists to solve the problem of aging. The prize also attracts new funding, brains, approaches and publicity to the mission of extending healthy life. What we are seeking - and expect to find - is not just a longer life for you, but a long, healthy, vibrant and productive life. 80, 90, 100 and even more healthy years. Cancer and Alzheimer's free. It's a tall order but one we are fully committed to."


Lysosomal Activity Declines With Aging

Lysosomes are roving garbage disposal and recycling units that exist in droves within your cells. One of their jobs is to break down damaged cellular machinery before it causes issues, and so that the component molecules can be reused. Another task is the disposal of unwanted or harmful biochemicals:

[Lysosomes] are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (wherein old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome).

If you've been following along these past few years, you'll know that autophagy is clearly very important in longevity. It is required for the life extension provided by calorie restriction, for example. If damaged cellular components are not cleared out rapidly, then their faulty operation will cause even more damage. This eventually spirals into what is known as the garbage catastrophe theory of aging. The cellular components of particular interest here are the mitochondria, the cell's powerplants: we know that mitochondrial damage contributes to aging, and that differences in mitochondrial function and structure between species correlate strongly with life span. It is very plausible that the primary reason autophagy is important in longevity is because this process destroys damaged mitochondria before they can cause further harm.

Given that lysosomes are the agents of autophagy, we should therefore be concerned if they fail or slow down with aging. Unfortunately, this is exactly what happens. There are at least two important processes underlying the failure of lysosomal function with aging. Firstly, there exist a great many biochemicals that lysosomes cannot break down. Once inside a lysosome, that junk is there to stay:

Lipofuscin is the name given to a gunk formed of many varied chemical byproducts of metabolism. It accumulates in your cells with age - and cause a great many problems in doing so. In particular, it accumulates in lysosomes, the recycling units of your cells that are tasked with breaking down unwanted chemical and components (the latter in the process called autophagy). Lysosomes in the old are bloated and inefficient, packed to the gills with lipofuscin that cannot be broken down by the enzymes available to your cells.

What to do about the accumulation of lysosomes rendered ineffective by biochemical junk? The SENS Foundation approach is research into a practical form of medical bioremediation:

The most promising approach is to enable cells to break the junk down so that [lysosomes] don't fill up after all. This can be accomplished by equipping the lysosome with new enzymes that can degrade the relevant material. The natural place to seek such enzymes is in soil bacteria and fungi, as these aggregates [such as lipofuscin], despite not being degraded in mammals, do not accumulate in soil in which animal carcasses are decaying, nor in graveyards where humans are decaying. This suggests that the micro-organisms present in soil have enzymes capable of breaking these aggregates down, and work now being carried on at Arizona State University has already confirmed this analysis.

The second process at work in the decline of lysosomal function was more recently established. Items to be recycled by lysosomes must be identified and steered to a lysosome, a process accomplished by cellular machinery that includes chaperone molecules and receptors on the lysosomes themselves. These lysosomal receptors decline with age, however, a change that may or may not result from the accumulation of biochemical junk discussed above.

The cells of all organisms have several surveillance systems designed to find, digest and recycle damaged proteins. ... One of these surveillance systems - responsible for handling 30 percent or more of damaged cellular protein - uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone ferries it towards one of the cell's many lysosomes ... Dr. Cuervo found that the chaperone surveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins.

Last year Cuervo demonstrated old mouse livers functioning as well as young mouse livers through genetic engineering of a breed that produced more lysosomal receptors. It remains to be seen whether this result holds for all tissues and organs, as well as what exactly is the root cause of age-related decline in receptors.

Lysosomal decline is typical of what researchers know of the causes of aging. There is a great deal of very detailed knowledge about the processes involved, some ongoing and very promising research, and a clear roadmap that describes how to produce therapies to reverse the problem. All that is missing is a vast funding effort, public awareness and support, and the will to develop those therapies. If the young of today age and die in the same way as their ancestors, it will be because we all chose to look the other way and do nothing.

Exercise and Arterial Stiffness

The list of specific age-related changes slowed by exercise continues to grow: "Just three months of physical activity reaps heart health benefits for [adults between the ages of 65 to 83] with type 2 diabetes by improving the elasticity in their arteries - reducing risk of heart disease and stroke ... An improvement was seen in the elasticity of the arteries of the group that performed the activity compared to those who didn't exercise. ... There was an impressive drop in arterial stiffness after just three months of exercise. In that time we saw a 15 to 20 per cent reduction. ... There seems to be a knee-jerk reluctance to getting these older adults to exercise yet we used a vigorous level of activity and didn't have any trouble keeping participants in our study. They enjoyed the activity. People always underestimate what older adults can do. ... Our first step was to prove that it was at all possible for older adults to have reduced narrowing in their arteries due to exercise. Now we want to find out just how rigorous the levels of activity need to be to demonstrate the same results."


Refuting Singer on Radical Life Extension

Certain breeds of bioethicist and economist are much alike: they spend a great deal of time and energy in building complex sophistry or mathematical constructions to try and convince us that true is false, and black is white. This is a grand waste of talent that might have otherwise produced real value. Here is an example from the IEET Blog: "Peter Singer argues that we should not proceed to develop a hypothetical life-extension drug, based on a scenario where developing the drug would fail to achieve the greatest sum of universal happiness over time. But that's the wrong test. ... If we ask, more simply, which policy would be more benevolent, we reach a different conclusion from Singer's: even given his questionable scenario, development of the drug should go ahead. A more pluralistic account of the nature of morality than used by Singer reaches a benevolent recommendation on life-extension technology. ... It may be that utilitarians, such as Peter Singer, are inevitably pushed toward 'total-view' thinking - which attempts to maximise the total amount of happiness in the universe - rather than toward a view that we should ensure the best possible lives for those people who will come to exist in the future. As a result utilitarians can, again paradoxically given the sympathies that underly their moral theory, can make policy recommendations that are not the most benevolent available."


Cartilage Engineering in India

The US is not the center of the world, and much of the development undertaken by US research groups is also underway elsewhere. For example: "A neocartilage developed by the Biological Sciences and Bio-Engineering Department of Indian Institute of Technology-Kanpur (IIT-K) may someday prove a boon for patients suffering from osteoarthritis of the knees. So far, the only recourse for such patients were knee transplantation and regeneration of cells through cell therapy and stem cell technology. For the last four years, Professor of Bio-engineering Ashok Kumar [has] been working on the neocartilage project. After successfully trying it on mice, the team is now looking forward to test it on bigger animals. For testing it on humans, the IIT-K is in discussion with a few government hospitals in Lucknow and Kanpur. ... The cells are grown on a polymer matrix, which provide a suitable microenvironment for them to develop into tissues. During physical and bio-chemical tests it has exhibited natural cartilage properties. ... After the successful experiments, we are now in a condition to replace the whole or a small part of a damaged cartilage."


Can Young Cells Be Protected From an Old Body?

One of the obstacles to rejuvenation of specific systems in the body through stem cell transplantation is that cells take their cues from the environment that surrounds them. Young cells are effectively damaged or suppressed by an old cellular environment. But there are signs that this effect could be diminished, and this research is one step in that direction: "Nanoscaffolds can play a central role in organ regeneration as they act as templates and guides for cell proliferation, differentiation and tissue growth. It is also important to protect these fragile cells from the harsh environment in which they are transplanted ... The research team created the scaffold to provide a substrate for cell adhesion and migration and to influence the survival of transplanted cells or the invasion of cells from surrounding tissue. ... Implanted stem cells are adversely susceptible to their new environment and quickly get old, but this study suggests a solution to conquer this problem. The self-assembling nanofiber scaffold (SAPNS) provides a niche for the encapsulated stem cells by slowing down their growth, differentiation and proliferation, as well as potentially minimizing the immune response, thus enhancing the survival rate of the implanted stem cells. This allows the implanted stem cells to [extend] their neurites to reach distant targets, thereby re-establishing the neural circuits. This combination of stem cells and SAPNS technologies gives a new hope for building up younger neural circuit in the central neural system."


Tengion to Hold IPO

I see that Tengion, Anthony Atala's tissue engineering company, has filed to go public.

Tengion, which discovers, develops, manufactures and commercializes a range of replacement organs and tissues, or neo-organs and neo-tissues, filed on Thursday with the SEC to raise up to $40 million in an initial public offering. ... The East Norriton, PA-based company, which was founded in 2003 and has yet to generate revenue, plans to list on the NASDAQ under the symbol TNGN. Its product candidates focus on combining technology with the body's intrinsic capacity to regenerate tissue to address urologic, renal, gastrointestinal and vascular diseases; there are six candidates in the pipeline. Net proceeds from the deal will be used for research and development, repayment of debt and general corporate purposes.

I believe this should be taken as an indicator of future strength in the market for tissue engineering, and likewise in progress towards growing a wider range of replacement organs from a patient's own cells. Why? Because especially unpleasant financial and corporate governance legislation of recent years - even by the standards of US bureaucrats - has squashed the US IPO market down to a shadow of its former self. The costs and liabilities placed on public companies and their officers are enormous now in comparison to ten or twenty years ago. To hold an IPO today you either have to be mad or very confident indeed in your ability to generate high levels of revenue; here, I think the latter is much more likely.

Antipodean Pharmaceuticals and their Mitochondrially Targeted Antioxidant

You might recall the work of Skulachev's research group in producing an ingested antioxidant compound that targets the mitochondria and extends life span in mice. Similarly, mice genetically engineered to produce more naturally-occurring antioxidants in their mitochondria also live longer. By way of comparison, all other forms of antioxidant examined to date generally do nothing for life span, and may even harm your health and longevity.

The plausible explanation for the effects of mitochondrially targeted antioxidants rests on the mitochondrial free radical theory of aging. In short, your mitochondria are powerplants, thousands of them in each cell of your body. They convert food into the chemicals used to power cellular processes, but emit damaging free radicals as a byproduct. Some fraction of aging is caused by the chain of events that occur as mitochondria progressively damage themselves with their own emissions. Thus anything that can soak up these free radicals at the source, before they cause any harm, should lower the rate at which biochemical damage occurs, and extend life span.

Now let me direct your attention to Antipodean Pharmaceuticals, a New Zealand based research group working to develop an antioxidant targeted to mitochondria. Their compound, called MitoQ, appears similar to the SkQ1 developed by Skulachev:

Antipodean's lead compound MitoQ (mitoquinone) is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents cell death. ... MitoQ is being evaluated as an oral treatment for liver inflammation that leads to fibrosis and is associated with metabolic dysfunction. The company is also investigating topical indications that involve mitochondrial dysfunction, including dermatologic applications and retinal degeneration.

It goes without saying that the company has no public aim to work on aging. This is the standard state of affairs, even overseas. In the US, the FDA does not recognize aging as a medical condition, and so will not permit any potential therapy to come to market. Regulators in many other markets are similarly inclined. Thus promising technologies of this sort are sidelined into those areas in which regulators allow development to proceed at all.

Here is a recent paper from the Antipodean folk, which demonstrates that this type of chemical is safe in mice. This result should probably be taken as reassuring for Skulchev's development process as well, given the similarities.

The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo.

These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice.

Which is good news for this line of research. It appears to work the way we think it works, and doesn't cause any apparent unwanted side effects.

ResearchBlogging.orgRodriguez-Cuenca S, Cochemé HM, Logan A, Abakumova I, Prime TA, Rose C, Vidal-Puig A, Smith AC, Rubinsztein DC, Fearnley IM, Jones BA, Pope S, Heales SJ, Lam BY, Neogi SG, McFarlane I, James AM, Smith RA, & Murphy MP (2009). Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free radical biology & medicine PMID: 19854266

Singularity University Executive Program

The Singularity University should be viewed as a form of targeted advocacy and outreach, aimed at people who are already or likely to be movers and shakers, in charge of significant resources. In that respect it is one part of the grand distributed effort to generate a research and development community capable of building the technologies we desire within our lifetimes. One of the topics covered is the biotechnology of engineered longevity, but take a look at their programs for a better understanding of the SU approach: "The SU Executive Program educates, informs and prepares executives to recognize the opportunities and disruptive influences of exponentially growing technologies and understand how these field affect your future, your company and your industry. The SU/EP is an Over-the-Horizon Radar for Executives showing you what is in the lab today and what will be in the marketplace in the next 5 to 10+ years. ... Meet top faculty, thought leaders, and CEOs in a range of exponentially growing technologies; Learn the core vocabulary and breakthrough concepts in Artificial Intelligence and Robotics, Nanotechnology, Biotechnology and Bioinformatics, Medicine and Human-Machine Interfaces, and Networks and Computing Systems; Understand the underlying drivers of exponential change; Visit top Silicon valley companies implementing these breakthroughs."


Coordinated Disorganization

There is still some debate over to what degree aging is programmed. I think there's a fair case to be made that some of the body's responses to stochastic biochemical damage are genetic programs - not all of which are helpful in the long term. That is what this evidence suggests to me, in any case: "Among noncoding RNAs, microRNAs may be one of the best known subgroups, due to their unique function of negatively controlling gene expression ... Thus gene expression can be repressed [by microRNAs] through post-transcriptional regulation, implemented as a 'dimmer switch', in contrast to the all-or-none mode of suppression. Work from our lab and others shows that during aging, dysregulated expression of microRNAs generally occurs in groups, suggesting that their actions may be functionally coordinated as a 'pack' by common transcriptional regulators; the accumulation of these 'pack' disorganizations may be the underlying culprit contributing to the pathoetiology of many age-dependent disease states. The fact that many microRNAs are coordinated in their expression, due to either the close proximity of their genomic locations or sharing the same transcriptional regulation, suggests that future strategies for correcting age-dependent microRNA disorganization may need to involve a system biology, rather than a reductionist, approach. Therefore, understanding age-dependent changes of microRNA expression in 'packs' may open an entirely new frontier, i.e. how particular groups of noncoding RNAs, functioning together, contribute to mechanisms regulating aging and longevity."


More From the Methuselah Foundation as the Year Closes

Year's end is traditionally a time for non-profits to look back, update their supporters, and accept a flurry of last minute donations. Here are a couple of additional messages from the Methuselah Foundation, aimed at the wider audience of people who have not yet paid much attention or made up their minds on engineered longevity and aging research:

A Drug for a Longer Life: The Greatest Discovery of 2009

want to share with you the most important word I've added to my vocabulary in 2009. Remember this word:


Rapa what? Rapamycin. It may not mean much to you now but there's a chance it will add 12 or more years to your life - an extra 12 healthy, productive years. Time you could use to accomplish your goals, fulfill your dreams and share your wisdom. Maybe you'll write a book, travel the world, spend time you're your grandchildren... even your great grandchildren.

In 2009 Methuselah Foundation awarded the first ever Lifespan Achievement Award to Dr. Z. Dave Sharp, University of Texas. We felt compelled to make this award when the amazing results of a study on rejuvenation of mice, carried out by the Intervention Testing Program of the National Institute on Aging (NIA), was published. This study showed unequivocally that mice lived longer when they took rapamycin, an immunosuppressant drug generally taken by recipients of donor organs to avoid rejection.

The Foundation's strategy these days is incorporating a great deal of work to grow the community of healthy life extension supporters: broadening the appeal, pushing on concepts that haven't yet been tried, and so forth. How does one persuade the common man in the street to be basically for engineered longevity in the same way that he's basically for curing named diseases like cancer and Alzheimer's? Here is one approach, the My Bridge 4 Life strategy that was announced earlier this year:

A Long Life Tool: the Perfect Gift

Sadly, many of us know someone who is battling a life threatening illness. Or maybe a friend or relative is providing care for someone with cancer or Alzheimer's or just overwhelmed by the negative effects of aging or poor health.

Methuselah Foundation is dedicated to extending healthy human life and that includes a right here, right now solution - My Bridge 4 Life.

My Bridge 4 Life is a resource for anyone who has been diagnosed with a chronic or life threatening illness. It is equally valuable to family, friends and caregivers of anyone with cancer, Alzheimer's, organ failure, diabetes and any number of other diseases that take away years and vitality. Simply stated, it puts a wellness plan in the hands of anyone on earth diagnosed with a life threatening challenge.

This is a way to speak to an audience - whilst helping them - who are perhaps more receptive than most when it comes to what has to be said about engineering away aging, frailty, and age-related degeneration or disease.

Longer Telomeres, Less Neurodegeneration

Here is one of many studies to show some correlation between longer telomeres and slower accumulation of age-related damage. Questions remain as to where telomere length fits into aging: is it more of a cause or more of a marker of other processes? From the abstract: "Telomere shortening is a marker of cellular aging and has been associated with risk of Alzheimer's disease. Few studies have determined if telomere length is associated with cognitive decline in non-demented elders. We prospectively studied 2734 non-demented elders (mean age: 74 years). We measured cognition with the Modified Mini-Mental State Exam (3MS) and Digit Symbol Substitution Test (DSST) repeatedly over 7 years. Baseline telomere length was measured in blood leukocytes and classified by tertile as 'short', 'medium', or 'long'. At baseline, longer telomere length was associated with better DSST score (36.4, 34.9 and 34.4 points for long, medium and short) but not for change in score. However, 7-year 3MS change scores were less among those with longer telomere length. ... Findings were similar after multivariable adjustment for age, gender, race, education, assay batch, and baseline score. ... Thus, telomere length may serve as a biomarker for cognitive aging."


Exercise: Good for the Brain

There exist any number of studies to demonstrate that exercise slows age-related degeneration of the brain. One obvious mechanism is a reduction in the type of damage that leads to vascular disease. Most of these are long-term investigations, but here is a comparatively short-term study demonstrating the benefits of exercise in the old: "To evaluate the effects of endurance exercise training (EET) on the cognitive status of healthy community-dwelling older adults, [a] randomized controlled trial was conducted involving community-dwelling older adults from the town of Pianoro (northern Italy). We randomized 120 healthy subjects aged 65-74 years, both genders, to treatment (N = 60) and control (N = 60) groups. The treatment consisted of 12 months of supervised EET in a community gym, 3 h a week. All participants were assessed both at baseline and after 12 months on an intention-to-treat analysis. Cognitive status was assessed by one single test (Mini Mental State Examination, MMSE). ... The control group showed a significant decrease in MMSE score, which differed significantly from the treatment group scores. The odds ratio for the treated older adults to have a stable cognitive status after 1 year, as compared to the control group, was 2.74 after adjustment for age, gender, educational level and several other possible confounders. Blood pressure, body mass index, waist circumference and serum cholesterol did not differ significantly between the two groups."


Video From the Manhattan Beach Project Longevity Summit

I see that video interviews and presentations from the recent Manhattan Beach Project Longevity Summit are available on YouTube. A number of folk from the pro-longevity community who don't normally show up in interviews online are featured, so head on over to the Project channel and see what you think. A selection follows:

Manhattan Beach Project Defined

A conference of leading scientists, entrepreneurs, anti-aging doctors held in Manhattan Beach, California on November 13-15, 2009. The goal of the event was to create real time lines and real budgets designed to completely change the face of aging.

Dave Kekich: The Bridge to Longevity

If we can keep ourselves healthy for just another 15 to 20 years there will be new technologies that can actually reverse aging.

Ray Kurzweil Addresses the 2009 Longevity Conference

Famed inventor and futurist tell scientists gathered at the 2009 Longevity Conference that we are "very close to a tipping point in human history." According to his projections, in 15 years we will be adding more than one year every year to YOUR lifespan.

Aubrey de Grey: The Role of Mitochondria DNA in Aging

The noted biogerontologist discusses the effects of accumulative damage to mitochondria and the impact this has on cellular aging and senescence.

Dave Kekich: How Does Society Benefit From Extreme Life Extension

Maximum Life founder Dave Kekich answers the conventional objections people raised to increasing the human lifespan.

I should note that some of the videos linked above are the opening segments of multi-part presentations. The channel lists its contents, so you'll figure it out.

Exercise and the Aging Immune System

This review suggests that some fraction of immune system failure in later life can be laid at the feet of a sedentary lifestyle over the years - and that starting to exercise when older is not going to reverse all of that decline. "The elderly population is at an unprecedented risk of infectious diseases and [cancer] due to apparently inevitable age-related declines in immunity. The 'immune risk profile' (IRP) is an array of biomarkers that has been used to predict morbidity and mortality in older adults. As it is generally accepted that middle-aged and elderly individuals who habitually participate in moderate-intensity exercise are less likely to incur an infection than their sedentary counterparts, this review addresses current knowledge on the effects of regular exercise on aspects of adaptive immunity as they relate to the IRP. Findings from cross-sectional studies mostly show enhanced immunity in physically active compared to sedentary older adults. These include greater T-cell responsiveness to mitogens in vitro, a reduced frequency of antigen-experienced and senescent [T-cells], enhanced IL-2 production and T-lymphocyte expression of the IL-2 receptor, longer chromosome telomere lengths in blood leukocytes and in vivo immune responses to vaccines and recall antigens. In contrast, the evidence from the available longitudinal studies that have used an exercise training intervention in previously sedentary elderly to improve similar immune responses is less compelling."


Autophagy and Sirtuin-1

We know that autophagy is required for the health and longevity benefits of calorie restriction. Here is more on that topic: "The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life span extending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy."


Trust But Verify and the Maes-Garreau Tendency

"Trust but verify" is a good way to lead one's life. Ideally, we'd never take anyone's word for anything, and have the time and means to dig up supporting evidence for any position or statement that we encounter. But who has the time for that? We have to organize our busy lives around blocks of selective ignorance, portions of human knowledge and culture wherein we choose to take statements at face value, or follow the consensus viewpoint without doing the necessary groundwork to validate it. Books can and have been written on how to best go about this: acquiring and processing information costs time, and time is the most valuable resource most us of possess.

There exist a growing number of people propagating various forms of the viewpoint that we middle-aged folk in developed countries may (or might, or certainly will) live to see the development and widespread availability of radical life extension therapies. Which is to say medical technologies capable of greatly extending healthy human life span, probably introduced in stages, each stage effective enough to grant additional healthy years in which to await the next breakthrough. You might think of Ray Kurzweil and Aubrey de Grey, both of whom have written good books to encapsulate their messages, and so forth.

Some people take the view of radical life extension within our lifetimes at face value, whilst others dismiss it out of hand. Both of these are rational approaches to selective ignorance in the face of all science-based predictions. It usually doesn't much matter what your opinion is on one article of science or another, and taking the time to validate science-based statements usually adds no economic value to your immediate future. It required several years of following research and investigating the background for me to feel comfortable reaching my own conclusions on the matter of engineered longevity, for example. Clearly some science-based predictions are enormously valuable and transformative, but you would lose a lifetime wading through the swamp of uselessness and irrelevance to find the few gemstones hidden therein.

As a further incentive to avoid swamp-wading, it is generally well known that futurist predictions of any sort have a horrible track record. Ignoring all futurism isn't a bad attention management strategy for someone who is largely removed from any activity (such as issuing insurance) that depends on being right in predicting trends and events. You might be familiar with the Maes-Garreau Law, which notes one of the incentives operating on futurists:

The Maes-Garreau Law is the statement that "most favorable predictions about future technology will fall within the Maes-Garreau Point", defined as "the latest possible date a prediction can come true and still remain in the lifetime of the person making it".

If you want to be a popular futurist, telling people what they want to hear is a good start. "You're not going to be alive to see this, but..." isn't a compelling opening line in any pitch. You'll also be more convincing if your yourself have good reason to believe in your message. Needless to say, these two items have no necessary relationship to a good prediction, accuracy in materials used to support the prediction, or whether what is predicted actually comes to pass. These incentives do not make cranks of all futurists - but they are something one has to be aware of. Equally, we have to be aware of our own desire to hear what we want to hear. That is especially true in the case of predictions for future biotechnology and enhanced human longevity; we'd all like to find out that the mighty white-coated scientists will in fact rescue us from aging to death. But the laws of physics, the progression of human societies, and advance of technological prowess don't care about what we want to hear, nor what the futurists say.

I put value on what Kurzweil and de Grey have to say about the potential future of increased human longevity - the future we'll have to work to bring into being - because I have performed the due diligence, the background reading, the digging into the science. I'll criticize the pieces of the message I don't like so much (the timescale and supplements in the case of Kurzweil, WILT in the case of de Grey), but generally I'm on board with their vision of the future because the science and other evidence looks solid.

But few people in the world feel strongly enough about this topic to do what I have done. I certainly don't feel strongly enough about many other allegedly important topics in life to have done a tenth as much work to validate what I choose to believe in those cases. How should one best organize selective ignorance in fields one does care about, or that are generally acknowledged to be important? What if you feel - correctly, in my humble opinion - that engineered longevity is very important, but you cannot devote the time to validate the visions of Kurzweil, de Grey, or other advocates of longevity science?

The short answer is trust networks: find and listen to people like me who have taken the time to dig into the background and form our own opinions. Figuring out whether ten or twenty people who discuss de Grey's view of engineered human longevity are collectively on the level is not too challenging, and doesn't require a great deal of time. We humans are good at forming accurate opinions as to whether specific individuals are idiots or trustworthy, full of it or talking sense. Fundamentally, this establishment of a trust network is one of the primary purposes of advocacy in any field of endeavor. The greater the number and diversity of advocates to have taken the time to go digging and come back to say "this is the real deal," the more likely it is that that they are right. It's easy, and probably good sense, to write off any one person's views. If twenty very different people are saying much the same thing, having independently come to the same viewpoint - well, that is worth spending more time on.

One of the things I think we need to see happen before the next decade is out is the establishment of more high-profile longevity advocates who discuss advancing science in the Kurzweil or de Grey vein: nanotechnology, repairing the molecular damage of aging, and so on. Two, or three, or five such people is too few.

An Update on Tissue Engineering of Corneas

From the Telegraph: "Russell Turnbull, 38, lost most of the vision in his right eye when he had ammonia sprayed into it as he tried to break up a fight on a late night bus journey home. The attack, which badly burned and scarred his cornea, left him with permanent blurred sight and pain whenever he blinked. Now however his sight has been almost fully restored thanks to a new technique where doctors regrow the outside membrane of his cornea from stem cells taken from his healthy eye. The new operation involves cutting away a millimetre squared section of his left eye complete with stem cells and growing it to 400 times that size in the laboratory. The new outer skin of the eye is then stitched onto the badly damaged cornea in place of the damaged membrane. The technique [has] been used on eight patients and for most of them including Mr Turnbull it has almost completely restored their vision."


Seeking Funding to Explain Granulocyte Cancer Therapy

A press release: "In an effort to accelerate the development of a cancer treatment based on innate cancer immunity, the Direct Oncology (DO) Foundation is launching an appeal to raise $100,000 to sequence cancer resistant mice at Wake Forest University. The project is being coordinated by Livly, a Silicon Valley based non-profit corporation dedicated to the development of sustainable cures for the major diseases plaguing humankind. ... The immune systems of the mice successfully fight off different types of advanced cancer. Immune cells from these Spontaneous Regression / Complete Resistance (SR/CR) mice can be used to protect other mice from advanced cancer. Evidence suggests that there is a single place in the SR/CR mouse's genome that confers the remarkable cancer resistance. Ironically, the gene for the cancer resistance has proven inaccessible to standard mouse genetic methods, and its identity and sequence have remained elusive. The progress of clinical efforts was hampered by lack of knowledge of the genetics underlying the cancer resistance."


Longevity Tends to Change Economic Behavior for the Better

People base their plans and their lives around how long they expect to live. With fewer years ahead, you are more willing to take risks and less willing to participate in long-term plans. But much of the value that we humans create and maintain in the world around us requires long-term planning and commitment. The waste inherent in modern democratic governments is a good illustration of what short-termism does to value: political appointees placed in stewardship of resources have no incentive to undertake the tasks necessary for long-term growth, and every incentive to squander the prospects for long term gains in favor of maximizing short term gains.

But what I said above about plans and time is true on every timescale. There are (probably largely unknown and unknowable) economic benefits and patterns of growth that cannot be realized today because people simply don't live long enough to be interested in discovering these possibilities. I believe this to be the case because there exist many forms of economic growth and industries today that were not undertaken or discovered in past centuries due to a much shorter adult life expectancy.

While wandering the wild places of the internet, I came across a paper on the burst of economic growth that took place in 18th century England. The paper makes a fine argument that the roots of this growth lie in a sudden increase in adult life expectancy - how many more years someone can expect to live on average once old enough to own property and make meaningful economic decisions. Those people who expect to be around longer make for better stewards of property, more diligent investors, and overall better engines of compound growth. Interestingly, the easiest historical life expectancy data to dig up is life expectancy at birth, which does not correlate well with economic growth. In the past few hundred years, life expectancy at birth has changed largely due to reductions in childhood mortality rather than gains in adult life span - and it is those gains in adult life span that are the true engine of growth.

But take a look at the full PDF paper - it's a good read, even for the layman. Economics at its best is a very clear assembly of ideas, with minimal resort to mathematics, I think:

During the 17th and 18th century the English economy underwent a dramatic transformation: its capacity to feed and increasing population increased impressively. ... Perhaps for the first time in the history of any country other than a land of recent settlement, rapid population growth took place concurrently with rising living standands.


The notion of life expectancy provides the most important tool to examine the phenomenon of mortality, taking into account the age structure of the population. Life expectancy at age x is the average number of years that a person of age x will still survive at a given date. The most commonly used indicator is e(0), life expectancy at birth (or at age 0), but sometimes other statistics like e(1), e(5), e(20), e(50), are also tabulated. Their main advantage is that they capture age-specific mortality profiles: for instance, an increase in mortality concentrated in the age-group between 20-25 (due, for instance, to a long war) would affect e(0) but not e(30) because the probability of survival, given that a person is already 30, does not change.

Decisions about future capital and consumption are not taken by the agent when he is born but, rather, when he is twenty or twenty five years old. Therefore, the relevant survivial profile for considering the influence of mortality over investment choices is given by adult life expectancy. In fact, making the distinction between e(0) and adult life expectancy is expecially important for our problem because adult mortality behaves in a completely different way from infant and child mortality in the first half of the 18th century: adult mortality rates decreased very sharply from the end of the 17th century, while infant and childhood mortality rates were unusually high between 1680 and 1750.


If life cycle inspiration was present in rural England in the 18th century, farmers who were becoming aware that old people were gradually living for longer periods must have been more concerned about their own means of subsistence in the future. This may have been an important stimulus to reduce consumption, increase savings and take into account longer horizons.

Savings are the root of investment, and it is investment that enables work to improve existing resources and develop new resources. The choice between saving (investment) or spending now (consumption) is fundamentally the choice between working on improvement or squandering that opportunity. Much of the paper concerns the economic mechanisms and choices that led to improvement in that era, such as use of land, changing the way in which existing agricultural technology was used, and so forth - all stemming from longer lives and longer horizons for investment.

When reading about transformative growth in economic activity and resulting changes in society due to enhanced longevity in the past, one has to wonder what might be in store for us in the years ahead. The proposed roots of 18th century progress are at work again today as human adult life expectancy continues to rise. None of the fundamental line items are meaningfully different between then and now: economic activity today might be more complex, but it is built upon the same truths of physics and human nature as it was hundreds of years ago. So many choices flow from our expectations of life remaining to us: what grand projects and greater wealth for all will be enabled through longer healthy lives?

Improving Cellular Reprogramming

With so many researchers working on it, potential improvements to the process of reprogramming normal cells into stem cells are arriving rapidly. Here is one example: "Scientists believe there is much promise for induced pluripotent stem cells: normal adult cells that have been manipulated to develop the stem-cell-like ability to differentiate into other types of cells, potentially to be used to repair damaged tissue and treat the ravages of disease. But making these so-called iPS cells is both time-consuming and inefficient. Now researchers [have] discovered a protein required to quickly and efficiently reprogram human skin cells to express embryonic stem cell genes. The finding could eliminate a major bottleneck in the generation of iPS and embryonic stem cells - that of removing molecular tags called methyl groups from specific regions of cellular DNA. Without this process of demethylation, the stem cell genes are silent in adult, or differentiated, cells. ... The mechanism of DNA demethylation in mammals has eluded us for decades. Now we've identified a protein involved in targeted DNA demethylation, and we've also shown that it's critically important in reprogramming adult cells to function more like their stem cell predecessors."


Coaxing Blood Vessel Growth With Hydrogels

From PhysOrg: "Regenerative medicine therapies often require the growth of functional, stable blood vessels at the site of an injury. Using synthetic polymers called hydrogels, researchers [have] been able to induce significant vasculature growth in areas of damaged tissue. ... Because hydrogels are very compatible with biological tissues, they are a promising therapeutic delivery vehicle to improve treatment of peripheral artery disease, ischemic heart disease, and survival of cell and tissue transplants. ... the researchers incorporated specific chemical cross-links into the gels so that they would maintain their structural integrity and only degrade in the presence of enzymes called matrix metalloproteinases that are typically expressed by invading cells. They also incorporated into the matrices a protein, vascular endothelial growth factor (VEGF), which stimulates the growth of blood vessels. ... Incorporating these cross-links controlled the release of VEGF from the matrix so that VEGF was only released as the matrix was digested by invading cells ... With the degradable implant that included growth factors, after two weeks we saw that new vessels were growing into and around the implant."


Half an Eye on the Progression of Nanotechnology

We should all keep an eye on progress towards molecular nanotechnology. It is a field that will first blossom when biotechnology is mature and in full swing, and the merging of the two will most likely lead to impressive technologies for medicine and human enhancement. Artificial immune systems, blood cells far better than the real thing, and tools capable of repairing the biochemical damage of aging, cell by cell. Plausibly, this will all happen while most of us remain alive to see it, even without allowing for major advances in human longevity taking place over the next few decades.

If you have an eye for long term trends in medicine, you should be watching for progress towards molecular manufacturing and dry nanotechnology. Much of what currently goes on under the heading of nanotechnology in medical and manufacturing industries is simply progress in nanoscale fabrication and application of devices using nanoscale fabrication - good stuff, especially for medical diagnostics, but still a way away from precise molecule-by-molecule mass manufacture. The level of progress towards dry nanotechnology today determines whether we will see the nanotechnologies of radical life extension arrive in 20 years, 30 years or 50 years.

The part of the future progress curve that interests me is the point at which costs and difficulties become minor enough for a widespread amateur community to gather and start work. That is where things really take off and start to accelerate, development becoming highly competitive and very inventive. We've seen this happen in software engineering with the growth of the open source community, and the early stages of this process are underway in biotechnology. But for all the prognostication on the future of nanotechnology, what can we say about where that is heading and where it is now? How long will it be before programmable nanomachines and nanofoundries are a basement project, just like wide swathes of life science engineering can presently be a basement project? I notice some thoughts on the matter from the nanotechnology folk:

Over on Metamodern, there's a discussion of whether advanced molecular manufacturing systems could be developed by a small private effort.

Drexler thinks it's not possible today, and I agree with him that it doesn't look very likely; enabling technologies are not yet at the point where a small effort can succeed. But what if special-purpose nanotechnologies become increasingly sophisticated, continually out-competing the possibilities of general-purpose manufacturing for another 20 years?


I have thought for years that, even if no one did any work toward general-purpose nanomanufacturing, around about 2030 it would be a moot point - it would be something that a university lab could cook up in a few semesters, but many of the applications would have been achieved already. So, if no one tries to develop a nanofactory, then in two decades or so we may have one - and it won't be that big a deal - at least not at first...

Triiodothyronine Levels and Human Longevity

Triiodothyronine is a thyroid hormone, one of the more important central regulators of metabolic function in mammals. Longer lived mammal species, such as naked mole rats, have markedly lower levels of this hormone. As it turns out, long-lived humans seem to have slightly lower levels of triiodothyronine as well: "The hypothalamo-pituitary-thyroid axis has been widely implicated in modulating the aging process. Life extension effects associated with low thyroid hormone levels have been reported in multiple animal models. In human populations, an association was observed between low thyroid function and longevity at old age, but the beneficial effects of low thyroid hormone metabolism at middle age remain elusive. ... We have compared serum thyroid hormone function parameters in a group of middle-aged offspring of long-living nonagenarian siblings and a control group of their partners, all participants of the Leiden Longevity Study. ... When compared with their partners, the group of offspring of nonagenarian siblings showed a trend toward higher serum thyrotropin levels [in] conjunction with lower free thyroxine levels [and] lower free triiodothyronine levels ... Compared with their partners, the group of offspring of nonagenarian siblings show a lower thyroidal sensitivity to thyrotropin. These findings suggest that the favorable role of low thyroid hormone metabolism on health and longevity in model organism is applicable to humans as well."


Glucose Restriction in Cell Cultures

One method of researching potential mechanisms of calorie restriction is to restrict glucose intake of cells in culture. Here that is shown to inhibit precancerous cells: "Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of [cancer suppressing gene] p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. ... Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches." You might recall other studies showing the practice of calorie restriction to reduce cancer risk.


The Slow Advance of Stem Cell Therapies

In countries like the US, the bulk of the cost in time and resources of producing therapies from scientific advances lies in satisfying regulatory bodies - a useless cost, a waste, in other words. Money that could have gone to making a better, safer product is instead squandered on hoop jumping. In the US, the Food and Drug Administration is draconian now and becoming worse with each passing year. All the incentives for political appointees and government employees at the FDA are aligned towards blocking new therapies rather than allowing them through. They will not be much blamed for an absence of new approvals - the unseen cost of regulation is not what is, but what might have been - yet will be greatly blamed for any new approval of a therapy that proves even slightly more risky than estimated. So the bar for new therapies is raised and raised, a little at a time.

Stem cell therapies are a good example of a working class of medicine that is essentially forbidden in the US. Stem cell treatments presently illegal to provide in the US have been available elsewhere in the world for some years now, offered by responsible providers who have worked to bring the best they can offer to customers. Regulation of medicine serves no purpose other than to prohibit what might be available; it is control for control's sake. But of course, you'll rarely read about therapies available elsewhere in the world in the US press - or at least not in the context of what is also presently forbidden by the FDA. Here is an example of a general interest article on the progression of stem cell therapies:

If you've just had your first heart attack, doctors may one day be able to reverse the damage done with stem cell therapy. An intravenous method of injecting stem cells into patients who had experienced heart attacks within the previous 10 days suggested that this method works to repair - not just manage - heart damage, a recent study found. The study is a step forward in a field in which a lot of approaches have been tried in animals and preliminary human trials, but none has been approved for widespread clinical use for heart patients.


The research, published in the Journal of the American College of Cardiology, were part of a phase I study that set out to show safety. The trial has moved on to phase II, which is taking place in 50 hospitals in the United States, said Dr. Joshua Hare, director of the Interdisciplinary Stem Cell Institute at the University of Miami's Miller School of Medicine and lead author of the study. "We're looking on the time frame here of five years, in the best-case scenario, to have approved cardiac stem cell therapies," Hare said.

Five years ago, the first tentative therapies of this nature were already taking place in Asia. Theravitae, based in Israel, Canada, and Asia, has treated hundreds with its similar Vescell technology over the past few years. There is no good reason why these technologies are illegal to provide in the US - only prohibition for its own sake. And this is one very small slice of the larger picture; a hundred advanced medical technologies delayed and not developed in the US because of the FDA.

Present circumstances and trends strongly suggest that medicine in far countries will be consistently more advanced than that available in the US in the decades to come. Plan on medical tourism for your future.

Sirtuin Research Continues

From ScienceDaily: "A new paper from MIT biology professor Leonard Guarente strengthens the link between longevity proteins called sirtuins and the lifespan-extending effects of calorie restriction. ... Sirtuins bring about the effects of calorie restriction on a brain system, known as the somatotropic signaling axis, that controls growth and influences lifespan length. ... The researchers genetically engineered mice whose ability to produce the major mammalian sirtuin SIRT1 in the brain was greatly reduced. Those mice and normal mice were placed on a calorie-restricted diet. The normal mice showed much lower levels of circulating growth hormones, demonstrating that their somatotropic signaling system was impaired, but calorie restriction had no effect on hormone levels of mice that could not produce SIRT1. In future work, Guarente plans to investigate the mechanism by which sirtuins regulate the somatotropic axis. The work could also help researchers and companies in their search for small molecules that modulate sirtuins for maximum benefit." You might recall that lowered growth hormone levels is one of the demonstrated ways to extend life span in mice.


"Immortality Will End in Communism"

Bryan Caplan demonstrates that there's no end to the pro-death nonsense that can be mined from the works of Leon Kass: "Kass concludes: 'Clearly, to avoid such strains and disasters [imagined to result from enhanced human longevity], great changes in social patterns and institutions would probably be needed, changes unlikely to occur except through strong centralized planning. The coming of such centralized planning will have consequences of its own, not all of them attractive or desirable, to say the least.' Since he's writing in 1983, I have to take the last paragraph as a thinly-veiled warning that, 'Immortality will end in communism.' I've heard of 'Better dead than Red,' but this is ridiculous! What's wrong with Kass' analysis? Well, it might make sense in a rigid caste society where sons follow in their fathers' occupational footsteps, and promotions are based on seniority. It might even be a good description of mediocre academic departments. But it's irrelevant for advanced capitalist economies. In a passably free labor market, talented young people don't have to wait for retirements to get promoted. If their current employer won't pay them their marginal productivity, somebody else will. Furthermore, even if ossified hierarchies ruled existing firms, the end result wouldn't be economy-wide stagnation and 'functional immaturity.' It would be new entry by firms run by young people on meritocratic lines. The creative destruction of the economy does not require the physical demise of any of its participants."


Genescient Raises More Angel Funding

Today I was prodded into noticing that Genescient has raised more angel funding for their work on longevity genes and the potential manipulation thereof. Congratulations are due; it isn't easy raising funds in the present market environment, and the Genescient folk did so whilst clearly stating they are working to extend healthy human life span. That last point isn't quite the albatross it used to be, but it's still a challenge in some quarters. So the more people who stand up to openly and seriously talk about extending human life span the better.

Genescient Corporation, a California genomic-health biotechnology company, received $500,000 in new angel investment, to help commercialize the company’s technology and to fund further research. The investment was made by private investors with an interest in the rapidly growing field of nutrigenomics, based on the science of epigenetics and its promise of healthy life extension. A spokesman for the investors, Douglas Arends, stated: "We are especially interested in the genomics work Genescient has completed to identify human genes of aging. This knowledge, gained from decades of selective breeding of model animals for longevity, will to lead to the production of nutrigenomic compounds in 2010. The plan is to build on this work and, in later years, to develop drugs aimed at treating age-associated chronic diseases and provide patients with healthy life extension. We are predicting that Genescient will become a leader in its field, with the knowledge that it now has providing it with a significant head start."

It is, I think, a sign of the times that $500,000 is enough to fund meaningful amounts of work in biotechnology. Go back a decade or two and that sum of money was a rounding error in the business of deciphering and manipulating human biochemistry. But biology and computing continue to be closely twined together, the cost and pace of research benefiting from the powerful and continuing growth in processing power per dollar.

Personally I'm not so hot on nutrigenomics; pills and metabolic tweaking continue to look to me like the road to nowhere, or at best the slow boat to China. I think the most useful output generated by Genescient's present phase of work will be knowledge that can be used to validate and adjust course on other research programs aimed at reversing aging:

I think the most useful output for the long term arising from the work taking place at Genescient will likely be a wealth of data on how gene expression changes occurring with aging relate to forms of biochemical damage that are thought to cause aging. Are gene expression changes responses to damage, or are they genetic programs that themselves cause damage? Or both, or neither? How important is each particular change? These are vital questions if your goal is to revert gene expression changes in search of beneficial effects, but this data will also help those who seek to directly repair the damage itself. There's no such thing as useless information in biotechnology.

Progress in Dental Tissue Engineering

The dentists are making good progress in developing tissue engineering techniques: "Italian scientists claim to be the first to have succeeded in using implants of dental pulp stem/progenitor cells (DPCs) for autologous [facial] bone regeneration in humans. Their technique was used to repair bone defects due to wisdom tooth problems in 17 patients. ... researchers suggest that the approach could also be applied to any other area of reconstructive and orthopedic surgery. ... The human trial [involved] the extraction and expansion of DPCs from the maxillary third molars (wisdom teeth) of 17 patients requiring wisdom tooth extraction. The cells were then seeded onto a collagen sponge scaffold. The resulting biocomplex was used to fill in the injury site left by the removed tooth. X-ray evaluation three months after autologous DPC grafting confirmed that the alveolar bone of treated patients had optimal vertical repair and complete restoration of periodontal tissue back to the second molars. Histological observations also demonstrated the complete regeneration of bone at the injury site. Optimal bone regeneration was evident one year after grafting."


Casting Aging as a Global Challenge

In this age of big government and multinational endeavors, most people respond favorably to the familiar language of global challenges. Here is an attempt to place aging in those terms at In Search of Enlightenment: "Global aging is real, it's man made, and it threatens the health and economic prospects of the global population, especially the developing world. ... Because humans, unlike feral animals, have learned how to escape the causes of death long after reproductive success, we have revealed a process that, teleologically, was never intended for us to experience. One might conclude, therefore, that aging is an artifact of civilization. ... biological aging, and population aging, bring unprecedented challenges. Aging individuals faced increased risks of morbidity and mortality. Chronic diseases like cancer, heart disease, stroke, arthritis, etc. are set to ravage the aging populations of the world. This means unprecedented numbers of humans will suffer years of frailty and disease. Chronic diseases have replaced infectious diseases as the greatest threat to global health. ... So what are we going to do about global aging? At the end of this century our children and grandchildren will look back and ask: What were they thinking? Did they not see how dire the consequences of global aging can be? Did they not care about protecting all future generations from the chronic diseases that ravage humans in late life?"


Another Run At Artificial Red Blood

It seems reasonable to expect artificial red blood cells to be widely available in the not too far future. A variety of methodologies have been tried with some success or are presently under development. As the capabilities of nanoscale engineering improve, artificial substitutes for blood cells will only become better. Here is an example of the present cutting edge:

Real red blood cells owe their astonishing agility to their "biconcave" or tyre-like shape. To create synthetic particles with the same agility, Samir Mitragotri of the University of California and his team got their inspiration from the way real red blood cells acquire their final shape in the body.

They start out as spherical cells which then collapse into mature red blood cells following exposure to various substances. Similarly, Mitragotri's team found that if they added small balls made of a polymer called PLGA to a particular solvent, the spheres would collapse into a biconcave shape.

The researchers coated these 7-micrometre across, tyre-shaped particles, in a layer of protein. When they dissolved away the polymer core, a soft biodegradable protein shell was left behind with the same mechanical properties as red blood cells.

When you're building cell-substitutes from scratch the opportunity exists to make them better than the real thing in some regards. For example, giving these artificial cells the ability to carry more oxygen than actual blood cells seems like a very plausible goal. I'm sure you can imagine other enhancements well within the capabilities of today's biotechnology: drug delivery, resistance to infection, control of inflammation, and so forth. But even enhanced delivery of oxygen on its own is a platform that might be capable of slowing the onset of some age-related disease - such as vascular dementia and other conditions related to reduced blood flow in small blood vessels.

Looking further ahead, to the era of medical nanomachinery and synthetic biology that will arrive later this century, red blood cell replacements that are hundreds of times more effective than the real thing are quite possible and plausible:

Each respirocyte can store and transport 236 times more oxygen than natural red blood cells. It can also monitor carbon acidity in the cell. Filled with these respirocytes, an adult human could hold his/her breath underwater for four hours. That person could also sprint at top speed for at least 15 minutes without taking a breath.

Raising the Bar on Bad Overpopulation Articles

I see that the work of the Gavrilovs on population trends with large increases in human longevity, funded by SENS Foundation, is reaching a wider audience. It is good to envisage a future in which we see less hysteric nonsense propagated about overpopulation: "In computer simulations, Gavrilov concluded that 'population changes are surprisingly slow in their response to a dramatic life extension. For example, we applied the cohort-component method of population projections to 2005 Swedish population for several scenarios of life extension and a fertility schedule observed in 2005. Even for very long 50-year projection horizon, with the most radical life extension scenario (assuming no aging at all after age 50), the total population increases by 35 percent only (from 9.1 to 13.3 million).' ... In other words, a population of immortal reproducing organisms can grow indefinitely in time, but not necessarily indefinitely in size, because asymptotic growth is possible ... The startling conclusion is that fears of overpopulation based on lay common sense and uneducated intuition are, in fact, grossly exaggerated. ... In brief, we found that defeating aging, the joy of parenting, and sustainable population size are not mutually exclusive. This is an important point, because it can change the current public perception that life extension necessarily leads to overpopulation."


A Year-End Message from the Methuselah Foundation

From the Methuselah Foundation: "The black market for human organs made headlines in 2009. What didn't make the daily news were the men, women and children who died each day because they did not get an organ or because the transplant they had failed. Failed to give them a long, healthy life. We can't stand by and let people die, or live in poor health, when an alternative is possible. That's why Methuselah Foundation invested in Organovo this year. We believe that [the] team at Organovo are creating a better way to replace aging or diseased organs. When Thomas Klauset Aurdal, a 23 year old student in Norway, heard we were supporting the work of Organovo, he sent a $1000 contribution. According to Thomas, who had a heart transplant when he was only 16 years old: 'I can see a world where dying patients don't have to risk death while waiting for a donor organ from a dead person and where the patient doesn't have to take a heavy immunosuppressant drug. Future generations of transplantation patients will have a better chance of getting the organs and they will have a better quality of life and life expectancy than I have.' ... We share Thomas's dream and know the discoveries and breakthroughs that lead to new organs will be fabulously useful in regenerative medicine all along the way. We call our long term strategy MLife Sciences ... Simply stated, it is where your donations go to be sure there is money available to turn promising research into practical solutions [that] lead to the possibility of you - of Thomas - of your family, living a long, healthy, vibrant and productive life. Thomas liked the idea of investing in proven research and development but knew his donation was too small to invest directly in a regenerative medicine company. $1000 is a very small amount to a venture capitalist but it's a lot of money to a student. But making a donation to Methuselah Foundation allows you to give whatever amount you choose. No donation is too small. If each of us makes a contribution, together we can become major contributors to a new, better, promising way to extend the lives of everyone suffering from organ failure."


Methuselah's Zoo

Is the research community doing as much as it might to extract value from the diversity in life span amongst mammals? Certainly there are those scientist who would like to be engaged in a great deal more sequencing and biochemical deciphering of long-lived animals. But on the whole, I think that less is taking place in this area of study than might be. See this paper from a noted gerontologist, for example:

As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mammals, like the bowhead whale, appear to survive 200 years or more. Another group of species may not be as absolutely long-lived, but they are remarkably long-lived for their body size and metabolic rate. These species include a number of bats, some of which live for at least 40 years in the wild, as well as the naked mole-rat, which is the same size, but lives nearly 10 times as long as the laboratory mouse. Together these exceptionally long-lived organisms have important roles to play in our future understanding of the causal mechanisms and modulation of ageing.

Bats and naked mole-rats in particular have already contributed in the following ways: (1) they have contributed to the abandonment of the rate-of-living theory and weakened enthusiasm for the oxidative stress hypothesis of ageing, (2) they have helped evaluate how the tumour-suppressing role of cellular senescence is affected by the evolution of diverse body sizes as well as diverse longevities, (3) they have shed light on the relationship between specific types of DNA repair and ageing and (4) they have yielded insight into new processes, specifically the maintenance of the proteome and hypotheses concerning how evolution shapes ageing. The continuing acceleration of progress in genome sequencing and development of more and more cross-species investigatory techniques will facilitate even more contributions of these species in the near future.

Why is it that whales, with many more cells than us and longer life spans to boot, aren't riddled with cancers? How is that naked mole-rats seem to evade cancer entirely? What biochemical mechanisms allow humans to live much longer than our closest relatives in the primate kingdom? It is clearly the case that some forms of mammal biochemistry are much more capable of producing long and healthy lives than our own, and that we don't fully understand why yet.

ResearchBlogging.orgAustad SN (2009). Methusaleh's Zoo: How Nature provides us with Clues for Extending Human Health Span. Journal of comparative pathology PMID: 19962715

RNA Editing Longevity Genes in Centenarians

A PLoS ONE paper: "The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. ... Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. ... Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan." How does this genetic contribution to longevity work? We'll have to wait for further investigation to move beyond correlation to explanation.


Gene Therapy and Stem Cells Versus Limb Ischemia

From ScienceDaily: "Blood vessel blockage, a common condition in old age or diabetes, leads to low blood flow and results in low oxygen, which can kill cells and tissues. Such blockages can require amputation resulting in loss of limbs. Now, using mice as their model, researchers [have] developed therapies that increase blood flow, improve movement and decrease tissue death and the need for amputation. ... In a young, healthy individual, hypoxia - low oxygen levels - triggers the body to make factors that help coordinate the growth of new blood vessels but this process doesn't work as well as we age. Now, with the help of gene therapy and stem cells we can help reactivate the body's response to hypoxia and save limbs. ... Our results are promising because they show that a combination of gene and cell therapy can improve the outcome in the case of critical limb ischemia associated with aging or diabetes. And that's critical for bringing such treatment to the clinic."


What Are These Guys Up To?

A blog-style site I've noticed at the edge of my vision of late is Immortal Humans. Based on a first glance, I relegated it to the spam blog / adsense content scraper bucket and proceeded to ignore it. It is sad but true that running ads (and especially Google-provided ads) on a site related to human longevity and aging is a very good indicator of worthlessness in this day and age. The worse end of the "anti-aging" marketplace has ensured that to be the case with their relentless transgressions of marketing norms and internet best practices. That whole culture of buyers and sellers is very much a foaming sea of fools and scum eagerly parting the gullible from their money - whilst simultaneously making it harder for folk like myself to advocate research into real longevity science. There is no love lost there, you can be sure; in a world where millions upon millions of dollars go towards educating people that "anti-aging" means makeup and fakery, it becomes that much harder to get a word in edgeways regarding the possibilities of actually extending the healthy human life span through science.

But back to the topic at hand. I noticed a press release from Immortal Humans today and went to take another look at the site based on it:

The publisher of, Andrej Lavrenc and his international team of research writers are on the constant look out for the latest developments in the field of stem cell research, bioscience, gerontology, current anti aging methods and drive towards human immortality. They are dedicated to documenting humankind’s quest for immortality and publishing related news as it happens. Life extension is no longer the fodder for science fiction novels due to considerable advances being made in the science of aging. Bioscience and technology experts have joined medical researchers and longevity authorities to investigate theories on slowing and even reversing the aging process. Amazing discoveries are being made in laboratories around the world and has those stories for you.

The content is low quality, but mostly a good deal closer to the sort of thing I write about than the sort of "anti-aging" nonsense you'll find on a spam blog. On the whole, Immortal Humans seems like the sort of evolution in topics relating to human longevity that we'd like to see: more on the actual longevity science and implications of aging research, and less on supplements, makeup, and magical thinking. As to the quality, well, I wasn't that great a writer when I started out, and now I've worked my way up to merely average.

So some free and unsolicited advice for the Immortal Humans folk from a fellow who makes no money writing online about longevity science and progress towards extended human longevity: if you want to be taken seriously, drop the optimized ads. If your primary driving goal in writing about something is to engineer clickthroughs and few-second view times, then you're not really writing about that topic at all, but instead simply piling up words aimed at algorithms rather than people. There's no talent or worth in that. The end result will be poor writing that reflects poorly on you, and ultimately makes everything you have to say suspect and ignored.

It's perfectly possible to make money via online content without falling into this trap - by writing things that are genuinely useful, insightful, or valuable. Take the high road in other words: write the content you want to write, write it well, and then figure out how to make money from it. Content first, monetization second.

Immortality Institute December Newsletter

From the Immortality Institute: "During this year-end holiday season I would like to take time to thank those who give. Despite all the trends and discussion pointing toward an open-source shared future and ubiquitous cheap resources derived from nanotechnology, in 2009 we still live in a world where 'money talks'. It is a necessary component of any organization including the Immortality Institute. During 2009, the Institute has spent nearly $30,000 cryopreserving a lifetime member, supporting anti-aging research, and providing student scholarships among other things. A significant part of the Imminst revenue stream is member donations. Even in this time of economic turmoil, hundreds of generous people have donated to support Institute operations and initiatives. With your continued support, the Institute can aim higher and accomplish more in coming years. So I extend heartfelt gratitude to all those who give time and money to help end the suffering of aging and the prevalence of death."


More Manhattan Beach Project Coverage

From the tech blogs this time: "Human life expectancy may see a hockey stick growth curve in the coming years as a result of leaps made in fields such as molecular nanotechnology, gene therapy, robotics, and regenerative medicine. Seizing the potential for radical longevity, an effort dubbed the 'Manhattan Beach Project', is a focused and targeted 'all-out assault on the world’s biggest killer - aging,' according to its founder David Kekich, President/CEO of Maximum Life Foundation. ... It consists of a group of researchers and entrepreneurs that have for years been collaborating on a scientific road-map to intervene in the human aging process and are disclosing their plan 'to start saving up to 100,000 lives lost to aging every day, by 2029.' In November '09, Kekich organized a Longevity Summit that brought together a number of leading scientists, visionaries, and experts on human aging and longevity for a discussion on the state-of-the-art research and the implications of their discoveries. Their goal is to develop a scientific and business strategy to make human life extension a real possibility within the next two decades."


Are Cells From Old People Still Good For Therapeutic Use?

Some nagging uncertainties remain on progress in stem cell medicine - and especially progress in reprogramming easily obtained somatic cells into patient-specific pluripotent stem cells. These uncertainties will be answered and addressed in the years ahead, but this one springs to mind today: it is possible that cells from older people may be altered or damaged in ways that prevent their effective use as-is in the sort of autologous stem cell therapies presently envisaged. That would be a setback for the first generation therapies: an entire additional industry would be required to fix or generate cells for use. We'd like to be able to repair arbitrary issues in stem cells anyway, but to have to do it to even get therapies running at all in the elderly would be a blow.

So it is reassuring to see papers appearing to show that cells from the old are as good by some measures as cells from the young, once reprogrammed:

Human induced pluripotent stem cells (IPSCs) have enormous potential in the development of cellular models of human disease and represent a potential source of autologous cells and tissues for therapeutic use. A question remains as to the biological age of IPSCs, in particular when isolated from older subjects. Studies of cloned animals indicate that somatic cells reprogrammed to pluripotency variably display telomere elongation, a common indicator of cell 'rejuvenation.'

We examined telomere lengths in human skin fibroblasts isolated from younger and older subjects ... While these results reveal some heterogeneity in the reprogramming process with respect to telomere length, human somatic cells reprogrammed to pluripotency generally displayed elongated telomeres that suggest that they will not age prematurely when isolated from subjects of essentially any age.

Good to know. Again, though, this is all a non-issue in the long term. In the long term, cells, genomes, and cellular components will be built entirely from scratch and altered in any arbitrary way to accomplish the task at hand. In the long term, we'll all be man-made machines. The real issue is how things go in the near term: whether those of us who will have to benefit from the therapies available two decades from now will have an easier or a harder time of it.

ResearchBlogging.orgSuhr, S., Chang, E., Rodriguez, R., Wang, K., Ross, P., Beyhan, Z., Murthy, S., & Cibelli, J. (2009). Telomere Dynamics in Human Cells Reprogrammed to Pluripotency PLoS ONE, 4 (12) DOI: 10.1371/journal.pone.0008124

The Autopsy Issue in Cryonics

One of the many ways in which we are far less free than our recent ancestors is that government employees regularly run roughshod over private agreements. For example, local officials essentially act as through they own your body in the case of autopsies, which presents a large issue for people who want to be cryopreserved on clinical death: "The nation's leading [cryonics] organization lost its bid Thursday to prevent an autopsy on a 48-year-old man who wanted his body frozen until he could be brought back to life. Hillsborough Circuit Judge Martha J. Cook told the county medical examiner to resume the autopsy on Michael Ned Miller, which was interrupted shortly after it began by a call from Alcor Life Extension Foundation Inc. of Scottsdale, Ariz. Cook denied Alcor's request for a stay pending an appeal of her order. 'The court will not interfere with (the medical examiner's) duty,' Cook said. ... the judge took no testimony. She said the law giving medical examiners the right to override private preferences about autopsies is clear. ... Alcor argued in court documents that an autopsy would 'seriously impair the cryonic process' and 'frustrate the purpose' of the body freezing: to keep his body preserved until some point in the distant future when scientists learn how to fix what killed him." Sadly, we live in age in which men serve laws, rather than vice versa.


On the Way to Artificial Eyes

The early foundations of artificial eyes are advancing, step by step: "Retinal implants are arrays of electrodes, placed at the back of the eye, which partially restore vision to people with diseases that cause their light-sensing photoreceptors to die. Typically, a camera embedded in glasses collects visual information and sends it to a computer that converts the images to electrical signals, which are then transmitted to the implant and interpreted by the brain. ... most people with implants can only make out fuzzy borders between light and dark areas. ... The Stanford implant would allow patients to make out the shape of objects and see meaningful images [and] has approximately 1,000 electrodes, compared to 60 electrodes commonly found in fully implantable systems. ... [it is] a silicon implant with tiny bridges that allow it to fold over the shape of the eye. ... The advantage of having it flexible is that relatively large implants can be placed under the retina without being deformed, and the whole image would stay in focus."


"Simply Slowing the Aging Process"

A recent research article caught my eye, but more for this opening paragraph than the actual science:

Aging is the single greatest risk factor for Alzheimer's disease. In their latest study, researchers at the Salk Institute for Biological Studies found that simply slowing the aging process in mice prone to develop Alzheimer's disease prevented their brains from turning into a neuronal wasteland.

The emphasis is mine. Can you imagine such a thing being written ten years ago? Now it's old hat. We're just slowing the aging process in mice here, nothing to see, move along now. There are probably more than a dozen methods demonstrated to significantly slow down the effective rate of aging in mice, and more are being discovered with each passing year.

But on with the rest of the research. Diseases of aging, like Alzheimer's, might be considered as end-states of damage accumulation. It's the point at which slowly accumulated wear and tear reaches a threshold at which matters spiral down rapidly into system failure. Different types of damage lead to different diseases when they reach the runaway failure point, but the named conditions of aging can be thought of as the most common failure modes for worn human biology. Thus it makes sense that alterations shown to slow aging - in the sense of slowing damage accumulation - also protects against these conditions:

"In this study, we went directly to the root cause of Alzheimer's disease and asked whether we could influence the onset of the disease by modulating the aging process," says first author Ehud Cohen, Ph.D., formerly a postdoctoral researcher in Dillin's lab and now an assistant professor at the Hebrew University-Hadassah Medical School in Jerusalem, Israel.

To answer this intriguing question, he slowed the aging process in a mouse model for Alzheimer's by lowering the activity of the IGF-1 signaling pathway. "This highly conserved pathway plays a crucial role in the regulation of lifespan and youthfulness across many species, including worms, flies, and mice and is linked to extreme longevity in humans," he explains. As a result, mice with reduced IGF-1 signaling live up to 35 percent longer than normal mice.


Although long-lived mice didn't show any of the cognitive or behavioral impairments typical of Alzheimer's disease till very late in life, their brains were riddled with highly compacted plaques.

"Although before it was thought that plaques are the causative agents of Alzheimer's disease, our results clearly support the emerging theme that they have a protective function," says Cohen. "As mice age, they become less efficient at stowing away toxic beta amyloid fibrils in tightly packed aggregates."

As you might be aware, basic Alzheimer's research and theories of Alzheimer's biochemistry are in a very fluid state. The conclusions of past years are challenged on a regular basis, and a new consensus has yet to emerge. The data continues to flood in - it's an exciting field to be a part of these days, wherein anyone might soon establish the right connection that makes all the contradictions and datasets fall into place.

Vigorous Regeneration of Axons

Via EurekAlert!, more signs that nerve regrowth will become an established medical procedure not too many years from now: "Brain and spinal-cord injuries typically leave people with permanent impairment because the injured nerve fibers (axons) cannot regrow. A study [now] shows that axons can regenerate vigorously in a mouse model when a gene that suppresses natural growth factors is deleted. ... [Researchers] used genetic techniques to delete two inhibitors of a growth pathway known as the mTOR pathway in the retinal ganglion cells of mice. (These cells constitute the optic nerve, which carries visual input from the retina to the brain.) Removing this inhibition brought about vigorous growth in injured axons, but not in uninjured axons, suggesting that something about the injury itself helps trigger axon regeneration. In the new study, [researchers] used a second set of genetic techniques in mice to delete a suppressor of inflammatory signaling, known as SOCS3, in retinal ganglion cells - and again saw robust axon growth after injury. The greatest effect was seen after one week, when there were also signs that the mTOR pathway was re-activated."


Multipotent Stem Cells in Skin

Multipotent stem cells can be found in the skin, potentially a low-cost source for the development of therapies: "Scientists have discovered a new type of stem cell in the skin that acts surprisingly like certain stem cells found in embryos: both can generate fat, bone, cartilage, and even nerve cells. These newly-described dermal stem cells may one day prove useful for treating neurological disorders and persistent wounds, such as diabetic ulcers ... the cells act like neural crest cells from embryos - stem cells that generate the entire peripheral nervous system and part of the head - in that they could turn into nerves, fat, bone, and cartilage. ... That gave us the idea that these were some kind of embryonic-like precursor cell that migrated into the skin of the embryo. But instead of disappearing as the embryo develops, the cells survive into adulthood. ... Stem cell researchers like to talk about building organs in a dish. You can imagine, if you have all the right players - dermal stem cells and epidermal stem cells - working together, you could do that with skin in a very real way."


Grow Fat and Lazy, and Vascular Dementia Awaits

Metabolic syndrome is a shorthand for the unfavorable changes that result from eating too much, exercising too little, and packing on the pounds of visceral fat. These lifestyle choices alter the operation of your biology for the worse: in most people they will cut short life expectancy, boost chronic inflammation, and raise the risk of suffering all of the common disabling and fatal age-related conditions, such as dementia, diabetes, heart disease, cancer, and so forth. If you let things rust, don't be surprised when they fail and fall apart more readily.

Degeneration of the mind is perhaps the worst consequence of a lifestyle of fat and indolence. Metabolic syndrome brings with it fat-induced chronic inflammation that significantly increases the risk of suffering a range of neurodegenerative conditions, such as vascular dementia - destruction occurring in the brain as a result of damage and dysfunction in small blood vessels. Here is a paper from the Italian Longitudinal Study on Aging to back up that claim with data:

We investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up. ... A total of 2,097 participants from a sample of 5,632 65-84 year old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria.


MetS subjects compared with those without MetS had an elevated risk of VaD ... Moreover, those with MetS and high inflammation had a still further higher risk of VaD [compared] with those without MetS and high inflammation. On the other hand, those with MetS and low inflammation compared with those without MetS and low inflammation did not exhibit a significant increased risk of VaD.

It is interesting to find a population with metabolic syndrome and low levels of inflammation: I would venture a guess that those people have a more active lifestyle rather than being blessed with better genes. It does indicate that the real bugbear behind the curtain is inflammation - but the existence of fortunate people doesn't make it smart for the rest of us to pile on the pounds assuming we'll be amongst the lucky few who retain lower risk profiles and lower levels of inflammation.

ResearchBlogging.orgSolfrizzi V, Scafato E, Capurso C, D'Introno A, Colacicco AM, Frisardi V, Vendemiale G, Baldereschi M, Crepaldi G, Di Carlo A, Galluzzo L, Gandin C, Inzitari D, Maggi S, Capurso A, & Panza F (2009). Metabolic Syndrome and the Risk of Vascular Dementia. The Italian Longitudinal Study on Aging. Journal of neurology, neurosurgery, and psychiatry PMID: 19965842

Commercial Stepping Stones Towards Artificial Organs

For a new field of research to thrive, there must be ways to make money from a partial product. In this way development can be incremental: make an advance and use revenues from it to fund the next step ahead. So it is for the development of artificial and tissue engineered organs, where one possible stepping stone involves improvements in cost and efficiency of testing new therapies: "Our artificial organ systems are aimed at offering an alternative to animal experiments. Particularly as humans and animals have different metabolisms. 30 per cent of all side effects come to light in clinical trials. ... The special feature, in our liver model for example, is a functioning system of blood vessels. This creates a natural environment for cells. We don't build artificial blood vessels for this, but use existing ones - from a piece of pig's intestine. ... All of the pig cells are removed, but the blood vessels are preserved. Human cells are then seeded onto this structure - hepatocytes, which, as in the body, are responsible for transforming and breaking down drugs, and endothelial cells, which act as a barrier between blood and tissue cells. In order to simulate blood and circulation, the researchers put the model into a computer-controlled bioreactor using a flexible tube pump ... This enables the nutrient solution to be fed in and carried away in the same way as in veins and arteries in humans. ... The cells were active for up to three weeks. This time was sufficient to analyse and evaluate the functions. A longer period of activity is possible, however."


More Attention Given to the Axolotl

From ScienceDaily: "a multi-institutional team of researchers [has] begun creating genomic tools necessary to compare the extraordinary regenerative capacity of the Mexican axolotl salamander with established mouse models of human disease and injury. Researchers want to find ways to tap unused human capacities to treat spinal cord injury, stroke, traumatic brain injury and other neural conditions ... The axolotl is the champion of vertebrate regeneration, with the ability to replace whole limbs and even parts of its central nervous system. These salamanders use many of the same body systems and genes that we do, but they have superior ability to regenerate after major injuries. We think that studying them will tell us a lot about a patient's natural regenerative capacities after spinal cord injury and nerve cell damage ... Only now have new genetic, molecular and cellular technologies as well as scientific knowledge of the salamander, mouse and human genomes and 'regeneromes' risen to a level where scientists can compare systemwide responses to injury. ... I am extremely hopeful with the discoveries being made in comparative regenerative biology that the questions surrounding cell and tissue regeneration in the human following injury or disease are going to be answered."


Amyloid: Junk That Builds Up Between the Cells

As we get older, many different types of errant and unwanted proteins, the chemical byproducts of metabolism, build up and accumulate between our cells. Collectively these are known as forms of amyloid, a term that might be familiar to you in connection with Alzheimer's disease, but there are many other types of amyloid beyond that implicated in the destruction that Alzheimer's brings to the brain. For example, the work of the Supercentenarian Research Foundation implicates a different form of amyloid in the deaths of the oldest old. Those people who - though good genes, good lifestyle choices, and good luck - manage to evade heart disease, cancer, and all the other common forms of age-related death are done in by amyloid in the end.

In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. "The same thing that happens in the pipes of an old house happens in your blood vessels," says Coles.

As one of the obvious and known forms of biochemical and structural change that occurs with aging, the buildup of amyloids is a target for the Strategies for Engineered Negligible Senescence (SENS):

Extracellular junk is aggregates of stuff that do not have any function and should ideally have been cleared out of the body, but have proven resistant to destruction. Extracellular junk is different from extracellular cross-linking - it refers only to substances that do not have any function, not even a biophysical one. Most of this junk is termed "amyloid" of one variety or another. You may have heard of one form of amyloid - Abeta, the stifling, web-like material that forms plaques in the brains of patients with Alzheimer's disease, and also (more slowly) in everyone else's.


A strategy for reversing the accumulation of such material is being pursued by several scientific teams, including researchers with Elan Pharmaceuticals: vaccination to stimulate the cells of the immune system to clear out the material. ... the cells may eventually encounter problems in fully digesting this material - but, if so, its degradation can still be engineered by [a bioremediation approach using enzymes discovered in bacteria].

As you might know, it is in fact not so clear-cut exactly how varying forms of amyloid cause their contributions to the damage and disease of aging. Under the SENS mindset, we should still proceed as rapidly as possible to establish ways to reduce amyloid buildup to youthful levels. It doesn't matter that we don't know all the details: the sum total of what we would like to achieve is to restore an aged biochemistry to the same state it was in when it was young. We know that increased amyloid is a change that occurs with aging, and we can see how to reverse it, so the most effective course of action is to build the necessary therapies as soon as we can, even if that means doing so in advance of a complete understanding of how amyloid damages us.

On the topic of the mechanisms by which amyloid is destructive to your cells, your metabolism, and ultimately your health and life, I noticed a recent paper I should point out, though you might prefer the popular science release format instead:

It was believed that amyloid fibrils - rope-like structures made up of proteins sometimes known as fibres - are inert, but that there may be toxic phases during their formation which can damage cells and cause disease. [But] scientists at the University of Leeds have shown that amyloid fibres are in fact toxic - and that the shorter the fibre, the more toxic it becomes.

"This is a major step forward in our understanding of amyloid fibrils which play a role in such a large number of diseases," said Professor Sheena Radford of the Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences. "We've revisited an old suspect with very surprising results. Whilst we've only looked in detail at three of the 30 or so proteins that form amyloid in human disease, our results show that the fibres they produce are indeed toxic to cells especially when they are fragmented into shorter fibres."

Amyloid deposits can accumulate at many different sites in the body or can remain localised to one particular organ or tissue, causing a range of different diseases. Amyloid deposits can be seen in the brain, in diseases such as Parkinson's and Alzheimer's, whereas in other amyloid diseases deposits can be found elsewhere in the body, in the joints, liver and many other organs. Amyloid deposits are also closely linked to the development of Type II diabetes.

Which is not terribly surprising, but it is still good support for the SENS approach of forging ahead. The only path to rapid success in engineering ways to reverse the damage of aging is to start early.

ResearchBlogging.orgXue, W., Hellewell, A., Gosal, W., Homans, S., Hewitt, E., & Radford, S. (2009). Fibril Fragmentation Enhances Amyloid Cytotoxicity Journal of Biological Chemistry, 284 (49), 34272-34282 DOI: 10.1074/jbc.M109.049809

False Objections to Cryonics

As pointed out at Depressed Metabolism a number of objections to cryonics presently doing the rounds are in fact objections to things that have little to do with cryonics: "Bryan Caplan has posted a number of blog entries that perfectly illustrate what happens when cryonics is not presented as a form of experimental long term critical care medicine but linked to other ideas such as transhumanism, mind uploading, and immortalism. One post is titled 'What's Really Wrong With Cryonics' but a close reading of the post and subsequent exchanges between Caplan and cryonics advocate Robin Hanson leave little doubt that this exchange is really about the technical feasibility of mind uploading and the nature of identity. These topics are of great philosophical and practical interest to some but have little relevance to the technical feasibility of cryonics. When a person goes in for surgery it is not common to engage medical personnel in abstract arguments about the nature of identity prior to induction of anesthesia. Similarly, when hypothermia is used to allow complete circulatory arrest in complex surgical brain procedures it is not common to object that this procedure puts the soul at risk. Even people who do not subscribe to the empiricist premise that underpins modern medicine have come to accept the procedures that are associated with it. Cryonics, as conceived and practiced by organizations like Alcor, is just an extension of the idea that metabolism can be reduced or stopped without inevitable irreversible death."


h+ Magazine on the Manhattan Beach Project

From h+ Magazine: "Just as the Manhattan Project was conceived in 1942 to beat the Germans to the atomic bomb during World War II, the 'Manhattan Beach Project' was founded as an 'all-out assault on the world's biggest killer - aging,' according to project organizer David A. Kekich. ... After nine years of research and collaboration, a group of entrepreneurs and scientists - many known to h+ readers - are disclosing their plan 'to start saving up to 100,000 lives lost to aging every day, by 2029.' A Longevity Summit in November 2009 - organized by Kekich - brought together a number of researchers on human aging and longevity for a discussion on the state-of-the-art research, the implications of their discoveries, and round table, cross-disciplinary discussions that may lead to new and accelerated results. ... The goal of the summit was 'to devise scientific and business strategies with the goal of demonstrating the capability to reverse aging in an older human by 2029.' ... Nanotechnology pioneer Robert Freitas - recipient of the prestigious 2009 Feynman Prize for Theory, in recognition of his pioneering work in molecular mechanosynthesis - gave a talk with Ralph Merkle on how medical non-biological nanotechnology will likely work in the next 20 years. 'The difference between good and bad health is how your atoms are arranged,' said Merkle. The goal of medical nanotechnology is to mobilize nanobots to patrol the body and its cells repairing damage as it occurs."


Transcripts From the 2009 Humanity+ Summit

The 2009 Humanity+ Summit was held this past weekend, and included a number of presentations on longevity science and transhumanist aspirations towards radical life extension. Bryan Bishop was kind enough to post transcripts, typed up in real time while he was there; those relating to engineered longevity are linked below:

Aubrey de Grey

Greg Fahy

Christine Peterson

Gregory Benford

Here is a line from de Grey's presentation:

We need to think properly about what aging is. Not just correctly. In an appropriate way that is conducive to a way about postponing to it.

Strategy matters greatly, in other words. The foundational point of de Grey's approach to aging is not so much the science, but the deliberate choice of goals and strategy that then leads to that science. If you want to save as many lives as possible as soon as possible, then you inexorably end up advocating a damage repair approach like de Grey's SENS.

Chase Community Giving: Vote for Longevity Science

Larger organizations are increasingly turning to contests and social networking events to determine some fraction of their charitable donations, which means folk like you and I can collaborate and agitate to steer money to our favored causes. Here is the latest: the Chase Community Giving contest at Facebook. Over the next week, votes will be accepted to establish a list of the top 100 charities. Each will receive $25,000, and then a second phase of voting and organizer selection will determine larger grants. I encourage you all to go and plug in your list of favored charities with the SENS Foundation and Methuselah Foundation at the top. But first, you might want to swing by the Immortality Institute, as the volunteers there have worked hard to produce a list of charities related to engineered longevity and links for quick voting: "Closing in on the end of 2009 we are presented with yet another golden opportunity to generate funds for the organizations and research that will pay great dividends towards a future of healthy human life extension. All you have to do is vote for your favorite charity!"


Organovo's Bioprinter

Via Singularity Hub, we learn that Organovo, which is recipient of a Methuselah Foundation grant, is close to releasing an early commercial bioprinter: "Need a new kidney? We'll just take some of your blood and in about six weeks grow you a new one. That's the promise of 3D bioprinting and one of the companies on the forefront of the technology just took a step closer to make it a reality. Organovo developed a research prototype of a bioprinter capable of producing very basic tissues like blood vessels. According to the recent press release, Invetech, Organovo's strategic partner, will be providing the company with commercial versions of their device in 2010 to 2011. While it is still limited to simple tissue structures (full organs are a long ways off), Organovo plans to deliver the printers to various research institutions interested in organ and tissue production." Once a concept becomes a software-driven machine, evolution and improvement tends to arrive rapidly. Ten years from now the prototypes will actually be printing complex organs.


More Cryonics UK Press Coverage

At the Cryonics UK website, you'll find a couple of interview videos and another article of press coverage: "Cryonics UK is a non-profit organisation set in place to provide assistance as necessary to those within the UK who wish for their body to be cryopreserved upon 'death'. The inverted commas around the word 'death' here are intentional. ... Science is constantly pushing the boundaries of what is considered
'dead'. Cryonics simply pushes that boundary a little further. By suspending a (legally dead) patient's body in liquid nitrogen, it is possible to prevent further deterioration of the body indefinitely. For obvious reasons, the initial cooldown is to be commenced as soon as possible after the patient is pronounced dead." You'll also find a response to a recent Guardian article that boasted a range of factual errors: "the whole thing is now irrelevant, as [the journalist] spent time with us sufficiently long ago that we've [since] moved to a different location, have a specialised clinic room for our kit and activities, [and are far more effectively organized]."


News From the Methuselah Foundation

The latest Methuselah Foundation newsletter is now available online. If you haven't been keeping up, you should dive into the archive over there and read the last couple of months of newsletters. The contents well illustrate the current focus and direction of the Foundation:

It's time to celebrate! It has been a great year at Methuselah and a great year for advances in aging research. Television, newspapers and websites have covered stories on calorie restriction, resveratrol and rapamycin. Leading biologists working in longevity research are finally grabbing the attention of other scientists (this year's Nobel Prize in Medicine is a very real example of this), the media and the general public. Methuselah Foundation is energetically working on new initiatives, connecting with more researchers and predicting some exciting announcements early in 2010.

The Foundation has added a couple of new ways to make modest charitable donations in the past couple of months:

As the end of the year nears, allow us to point out two new ways in which you can support Methuselah Foundation causes without digging out your checkbook. Firstly you can donate your used vehicle through Cars 4 Causes: this is tax deductible and Cars 4 Causes makes the donation a smooth process. Secondly, supporters can now obtain a credit card through Capital One printed with the Methuselah Foundation logo. 1% of every purchase you make using this card is automatically donated to Methuselah Foundation and Capital One will donate $25 after you make your first purchase.

Also worth mentioning is that comparatively few slots remain in the 300, the select group of donors who commit to donate $25,000 over the next 25 years. Most 300 members are folk of modest means who have resolved to give a few dollars a day to help advance the cause of longevity science. The names and messages of the 300 will be inscribed upon a monument built to last for millennia, a fitting tribute to their vision and commitment:

Last Call! Many thanks to our special group of donors, the 300. Responding to the Methuselah Foundation challenge to contribute $85 a month for 25 years, this farsighted group has made the progress you read about in this newsletter possible. There are a few remaining slots left, join now and your donation will go to work immediately funding innovative technology that will change science forever. As a 300 member you will receive advance notice of news and events, have the opportunity to participate in exclusive webinars, receive a monthly email from Dave Gobel and have the satisfaction of knowing your gift will result in extended healthy life for yourself, your family and all humanity.

You should read Michael Rae's article on why he joined the 300 - it is a fine argument for stepping up to the plate and doing something in support of engineered longevity and the defeat of aging.

On Life Span Differences Between Primates

Via ScienceDaily, an interesting theory: "In spite of their genetic similarity to humans, chimpanzees and great apes have maximum lifespans that rarely exceed 50 years. The difference, explains USC Davis School of Gerontology Professor Caleb Finch, is that as humans evolved genes that enabled them to better adjust to levels of infection and inflammation and to the high cholesterol levels of their meat rich diets. ... these evolutionary genetic advantages, caused by slight differences in DNA sequencing and improvements in diet, make humans uniquely susceptible to diseases of aging such as cancer, heart disease and dementia when compared to other primates. ... Over time, ingestion of red meat, particularly raw meat infected with parasites in the era before cooking, stimulates chronic inflammation that leads to some of the common diseases of aging. ... ApoE3 is unique to humans and may be what Finch calls 'a meat-adaptive gene' that has increased the human lifespan.
However, the minor allele, apoE4, when expressed in humans, can impair neuronal development, as well as shorten human lifespan by about four years and increase the risk of heart disease and Alzheimer disease by several-fold. ApoE4 carriers have higher totals of blood cholesterol, more oxidized blood lipids and early onset of coronary heart disease and Alzheimer's disease."


Exercise Boosts Telomerase, Reduces Erosion of Telomeres

Regular exercise is good for you, and a great weight of scientific studies back up that statement. Insofar as the degenerations of aging go, the present consensus appears to be that exercise in humans slows aging to around the same degree as calorie restriction in humans. Where else could you go to find a fairly cost-effective way of extending your healthy life expectancy by a decade or so? (Or from the glass half empty perspective, we might add lack of exercise and eating too much to the list of ways to shorten your healthy life expectancy by a decade or so - like smoking, for example). The multiple mechanisms involved in producing the benefits of calorie restriction and exercise are incompletely understood but known to overlap to some degree: hormesis, for example, heat shock proteins, and lower amounts of of visceral body fat. But on either side there are likely distinct processes at work. There is every reason to expect exercise and calorie restriction practiced together to produce greater benefits than just one or the other.

Here is something interesting noted in a recent research paper - though you might derive more value from the popular science release:

Long-term exercise training activates telomerase and reduces telomere shortening in human leukocytes. The age-dependent telomere loss was lower in the master athletes who had performed endurance exercising for several decades.


"The most significant finding of this study is that physical exercise of the professional athletes leads to activation of the important enzyme telomerase and stabilizes the telomere," said Ulrich Laufs, M.D., the study's lead author and professor of clinical and experimental medicine in the department of internal medicine at Saarland University in Homburg, Germany. "This is direct evidence of an anti-aging effect of physical exercise. Physical exercise could prevent the aging of the cardiovascular system, reflecting this molecular principle."

This is in one cell population amongst thousands, of course - and there still remain questions about telomere biology and its relationship to age-related degeneration. Is it more of a cause of aging or more of a marker of aging - is telomere shortening a consequence of mitochondrial DNA damage, for example? That damage is the villain in the mitochondrial free radical theory of aging. We know that exercise correlates with lower levels of mitochondrial DNA damage, and it looks much as though mitochondrial DNA damage correlates with shorter telomeres. At this point there are all sorts of plausible theories floating around - more plausible on the mitochondrial side of the pool from where I stand - but the telomere researchers and mitochondria researchers haven't hammered in that last stake to prove root causes beyond any reasonable debate.

This is one of the many areas in which the Strategies for Engineered Negligible Senescence approach shines. We have a list of items that change with aging: here (a) mitochondrial DNA, (b) telomere length. We could spend an age working on a complete understanding, or we could instead start work immediately on methods to reverse both changes. It researchers can reverse all the biochemical changes of aging we know of - and there is good reason to believe researchers know of all the important ones in some detail - then it doesn't matter which are secondary, which are primary, or how exactly they work and interconnect. If your goal is to reverse aging, or rather if your goal is primarily accomplishment rather than primarily knowledge accumulation, then you engineer your way though uncertainty towards the most likely and comprehensive fix for the problem at hand.

Consider: just as our ancestors didn't need a formal mathematics of architecture and precision materials science to engineer fine bridges, we who stand at the dawn of the biotech century don't need a complete understanding of human biochemistry in order to reverse the damage of aging. Our longevity therapies will be pretty clunky compared to what will come with complete understanding, but they will work, and billions will be saved from suffering and death because we didn't wait around when we could have been getting the job done.

ResearchBlogging.orgWerner, C., Furster, T., Widmann, T., Poss, J., Roggia, C., Hanhoun, M., Scharhag, J., Buchner, N., Meyer, T., Kindermann, W., Haendeler, J., Bohm, M., & Laufs, U. (2009). Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall Circulation DOI: 10.1161/CIRCULATIONAHA.109.861005

A View of Technological Development

From h+ Magazine, some thoughts on the development of transhumanist technologies, such as the repair of aging and radical life extension: "Max More has spoken out against the perception of a technological singularity as an inevitable future event, fearing this is a meme too prone to being hijacked by our tendency to believe in a higher power that will solve our problems for us. Let us therefore adapt technological mount improbable to take into consideration the uncertainty inherent in current transhuman speculations. Technological mount improbable is a mountain range covered by clouds. We cannot see the peaks that stand for cures for aging, artificial general intelligence, or productive nanosystems. We suspect such peaks exist, others claim they do not. One thing is certain. Even if they do exist, our vision is not yet clear enough to allow us to see how to climb up there. There are many paths winding their way along the mountain range. Some may allow us to reach a peak in a shorter time than you might have thought possible. They stand for new technologies such as improved gene-sequencing, or improved knowledge such as an overall theory of how the mind works. With luck and effort, we may find ourselves on such paths and ascend to the peaks of artificial general intelligence (AGI), etc., in years or decades rather than centuries. But there are also paths that lead to dead ends, by which I mean incorrect hypotheses regarding the way to treat aging, how to code artificial intelligence, and so on."


More on Methionine Restriction

Researchers continue to explore varying forms of protein restriction in lower animals: "The fruit flies were fed a diet of yeast, sugar and water, but with differing amounts of key nutrients, such as vitamins, lipids and amino acids. The researchers found that varying the amount of amino acids in the mixture affected lifespan and fertility; varying the amount of the other nutrients had little or no effect. In fact, when the researchers studied the effect further, they found that levels of a particular amino acid known as methionine were crucial to maximising lifespan without decreasing fertility. Adding methionine to a low calorie diet boosted fertility without reducing lifespan; likewise, reducing methionine content in a high calorie diet prolonged lifespan. Previous studies have also shown that reducing the intake of methionine in rodents can help extend lifespan. ... By carefully manipulating the balance of amino acids in the diet, we have been able to maximise both lifespan and fertility. This indicates that it is possible to extend lifespan without wholesale dietary restriction and without the unfortunate consequence of lowering reproductive capacity."


Niemals Alt! Ending Aging Translated to German

Aubrey de Grey and Michael Rae's Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime is now translated into German by a volunteer team, and published through Transcript:

The title, as you can see is "Niemals alt!" - Never Old, or Never Get Old, or Never to Become Old depending on your chosen engine of translation. German sensibilities demand a dark cover for such topics, it seems. In any case, congratulations are due for the volunteer translators. As I remarked when the Russian translation became available:

translation of a scientific work is never easy, especially when its focus is on research that is still cutting edge. Much of the crucial terminology in new fields is essentially made up from whole cloth or built of unusual compound words that draw on language roots and traditions of nomenclature that English and Russian may not have in common. In addition, precision of translation is important, as positions of understanding are built up over many succeeding steps - an incorrectly translated early stage can render whole pages of information nonsense.

The same is true for English and German of course, though at least the languages have closer roots in tongues of antiquity. The translation is a challenging job well done, the reward being an expansion of that fraction of the global population exposed to the ideas and potentials of longevity science.

Ovaries and Mammalian Longevity Again

Manipulating, removing, or transplanting ovaries has been shown to influence longevity in mammals - quite dramatically in the case of mice. Here are more examples, this time in dogs and humans: "The researchers collected and analyzed lifetime medical histories, ages and causes of death for 119 canine 'centenarians' - exceptionally long-lived Rottweiler dogs [and compared them] to a group of 186 Rottweilers that had usual longevity ... Like women, female dogs in our study had a distinct survival advantage over males. But taking away ovaries during the first four years of life completely erased the female survival advantage. We found that female Rottweilers that kept their ovaries for at least six years were four times more likely to reach exceptional longevity compared to females who had the shortest lifetime ovary exposure. ... The pet dog research [mirrors] the findings of the Nurses' Health Study published this summer by Dr. William Parker ... Parker's group studied more than 29,000 women who underwent a hysterectomy for benign uterine disease. The findings showed that the upside of ovary removal - protection against ovarian, uterine and breast cancer - was outweighed by increased mortality from other causes. As a result, longevity was cut short in women who lost their ovaries before the age of 50 compared with those who kept their ovaries for at least 50 years."


2009 Humanity+ Summit in Irvine, December 5th

This coming weekend, the 5th, sees the 2009 Humanity+ Summit held in Irvine, California: "The goal of Humanity+ is to support discussion and public awareness of emerging technologies, to defend the right of individuals in free and democratic societies to adopt technologies that expand human capacities, and to anticipate and propose solutions for the potential consequences of emerging technologies. ... What is going to be like to be a human in this next phase of technological progress? How can we get our heads around it so when it arrives we're best prepared to deal with it? We foresee the feasibility of redesigning the human condition, including such parameters as the inevitability of aging, limitations on human and artificial intellects, unchosen psychology, suffering, and our confinement to the planet earth. The possibilities are tremendously broad and exciting." The program includes a session on longevity science and progress towards enhancing the human life span.


A New Method of Extending Life Span By a Third in Mice

There is no shortage of theorizing as to the root cause of the difference between male and female life expectancy in humans. Is it genetic, the influence of hormones on known longevity genes, or dietary (such as via a lower calorie intake in women on average). Or perhaps it is related to other lifestyle choices that differ in the aggregate between genders, such as risky behavior or smoking? Does this difference in longevity involve modification of any of the known mechanisms that contribute to differing rates of biological aging between individuals, or is it something else?

It's all up in the air and still open for some researcher to make his or her name by developing a definitive answer. This, of course, remains true for so much of human biology - there is a lot of work left to do. But here is a theory on gender-based longevity differences that accompanies an intriguing method to engineer extended longevity in mice:

mice created from two female genomes (bi-maternal (BM) mice) lived an average of 186 days longer than control mice created from the normal combination of a male and female genome. The average lifespan for the type of mice used in the study is between about 600-700 days, meaning that the BM mice lived approximately a third longer than normal.


The researchers checked the weight of the mice at 49 days and 600 days (around 20 months after birth) and found that the BM mice were significantly lighter and smaller than the control mice. The BM mice also seemed to have better immune systems, with a significant increase in one type of white blood cell, eosinophil.


We believe that the most likely reason for the differences in longevity relates to the repression of a gene called Rasgrf1 in the BM mice. This gene normally expresses from the paternally inherited chromosome and is an imprinted gene on chromosome 9 associated with post-natal growth. Thus far, it's not clear whether Rasgrf1 is definitively associated with mouse longevity, but it is one of the strong candidates for a responsible gene.


Our results are consistent with models based on sex-specific selection of reproductive strategies, e.g. male individuals maximizing fitness by an intense investment in reproduction by way of a larger body size in order to achieve more breeding opportunities, resulting in shorter longevity…. In contrast, female individuals usually do not engage in such costly male behaviours and instead tend to optimize their reproductive output by conserving energy for delivery, providing for offspring, foraging and predator avoidance. Our results further suggested sex differences in longevity originating at the genome level, implying that the sperm genome has a detrimental effect on longevity in mammals.

That last paragraph is the bullet point on male-female longevity differences: it's the genes, evolution did it, and the biochemistry is just an implementation detail. At which point we'll drop that line of thinking for the moment to focus on the fact that here is demonstrated a previously unknown 30% life extension mechanism in mice that - at first glance at least - appears to be unrelated to calorie restriction. There aren't too many of those yet.

The Vitae Institute

The Vitae Institute is another of the modest and diverse initiatives sprung forth from the healthy life extension community in recent years. "The Vitae Institute is a 501(c)3 non-profit organization incorporated in 2006 to forward a scientific understanding of the mechanisms of aging and to develop technology and therapies to cure age-associated pathologies. Despite the existence of many organizations formed for the purpose of elucidating the mechanisms of aging and developing life extension technology, few contribute to these purported ends. I therefore believe that with the activities and ideology described on this website, the Vitae Institute is poised to play a significant role in accelerating the realization of bona fide life extension technologies." The Institute mission and history page is good material and well worth your time to read. Their take on the state of aging research and what is required to move forward seems good; very similar to that of the Methuselah Foundation and related advocates.


Aubrey de Grey in a Webcast on

Biomedical gerontologist and advocate for engineered longevity Aubrey de Grey participates in this CNN webcast: "Geneticist Aubrey de Grey is the Chief Scientific Officer of SENS Foundation, which researches and promotes regenerative medicine. He said that techniques such as stem cell therapy, gene therapy and tissue engineering could one day be used in combination to let humans live for hundreds of years. ... The real advantage of applying regenerative medicine to the problem of ageing is that we can actually turn the biological clock backwards. We [will be able to] take people who are already middle aged, or perhaps older, and turn them back to having a lower biological age. ... In the run up to the Webcast, CNN readers submitted questions for the panel. One asked if living for a 1,000 years would mean spending the last 200 years of your life in a nursing home. De Grey answered that regenerative medicine has the potential to stop the degeneration process, meaning people could stay in a youthful state indefinitely. The panelists agreed that dramatically increasing human life expectancy would have huge consequences for society and the economy. But they added that, rather than being a huge drain on healthcare systems, providing regenerative medicine on a widespread basis could actually benefit the economy, cutting down on medical costs by eliminating chronic illnesses like heart disease and cancer."