Longevity Meme Newsletter, January 04 2010

January 04 2010

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- The Breakdown of Cellular Recycling With Aging
- An Update on Medical Bioremediation
- Considering the Outer Limits of Bioprinting
- Discussion
- Latest Healthy Life Extension Headlines


One facet of the degenerations of aging is, in effect, a garbage catastrophe. The garbage collection mechanisms within your cells are gradually overwhelmed by junk they cannot deal with:


"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. [We] should therefore be concerned if they fail or slow down with aging. Unfortunately, this is exactly what happens."

Lipofuscin is the name given to a gunk formed of many varied chemical byproducts of metabolism. It accumulates in your cells with age - and causes a great many problems in doing so. A cell follows the standard garbage collection plan and throws all of its lipofuscin into its lysosomes - but the expected recycling process never happens, and that lipofuscin gradually accumulates. Lysosomes that become packed full of this lipofuscin cannot perform their jobs effectively. As a result, other unwanted biochemicals and dysfunctional biochemical machinery in the cell are left unrecycled. This state of affairs eventually spirals out of control, leading to malfunctioning bodily systems and contributing to a range of age-related conditions, including atherosclerosis and macular degeneration.


So we all have failing, junk-ridden lysosomes - what can be done to reverse this situation? One project currently undertaken by the SENS Foundation lays the groundwork for therapies based on bacterial enzymes that can remove this unwanted chemical junk. The lifting of that burden should restore our cellular garbage collection systems to a youthful and energetic state. A recent update on this research is found in the latest issue of Rejuvenation Research. Progress is as predicted so far:


"Bioremediation is the process of using plants and microorganisms (or aspects of their biochemistry) to restore a damaged or polluted environment. Medical bioremediation applies this same philosophy to the aging body - many aspects of aging can be thought of as having roots in damage and pollution at the level of our cells and cellular machinery.

"Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. ... We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with [the ability to break down these unwanted chemical pollutants]. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. ... We also discovered that soil fungi, plants, and some bacteria possess [enzymes] that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration."

"The next steps in this development cycle will involve establishing methods to introduce new enzymes into the body and determine which of those discovered are safe for use - which of course will require more fundraising. Because we humans can tolerate several decades of buildup in unwanted biochemicals like 7-ketocholesterol and A2E without undue harm, it seems plausible that a treatment similar to a course of drugs or chemotherapy will result at the end of the day. It will be a procedure that a person undergoes once every 20 years or so, in which the body is temporarily suffused with enzymes that clear out unwanted chemical gunk, thereby restoring the cellular recycling machinery of the lysosomes to pristine condition."

If you believe, as do I, that this work is important and progress should be rewarded, then make a donation to the SENS Foundation:



Great progress is presently being made in the use of rapid prototyping or three-dimensional printer technology for tissue engineering. The first printed organs may be turned out in the early 2020s:


"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. ... 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?"


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




An interesting paper: "Many laboratory models used in aging research are inappropriate for understanding senescence in mammals, including humans, because of fundamental differences in life history, maintenance in artificial environments, and selection for early aging and high reproductive rate. Comparative studies of senescence in birds and mammals reveal a broad range in rates of aging among a variety of taxa with similar physiology and patterns of development. ... Individuals of potentially long-lived species, particularly birds, appear to maintain high condition to near the end of life. Because most individuals in natural populations of such species die of aging-related causes, these populations likely harbor little genetic variation for mechanisms that could extend life further, or these mechanisms are very costly. This, and the apparent evolutionary conservatism in the rate of increase in mortality with age, suggests that variation in the rate of senescence reflects fundamental changes in organism structure, likely associated with the rate of development, rather than physiological or biochemical processes influenced by a few genes. Understanding these evolved differences between long-lived and short-lived organisms would seem to be an essential foundation for designing therapeutic interventions with respect to human aging and longevity." You might compare this with the strong correlations in life span and mitochondrial structure between mammals, and other thoughts on birds, metabolic rate, and aging.

A good survey of the next generation of cancer therapies can be found at Emergent Fool. I do not expect cancer to be a major threat to health in 2030 thanks to the development of robust cures for even late stage metastasis. "Biris and Zharov are making some exciting progress in using nanotubes to tag and then track cancer cells inside the body as they move around. They propose to kill the cancer cells by heating up the nanotubes using lasers ... The immune system is really good at identifying and killing cells behaving badly (although the majority of the time the immune system's targets are foreign invaders like viruses). But what if we could boost the immune system so that it was better able to deal with cancer cells? Essentially create a vaccine for cancer. ... Modifying genes, either by enhancing tumor suppressors or reducing tumor promotors, has been a popular appoach in recent years. Often the approach has been to focus on individually important genes or to try to find exhaustive sets of genes which, when modified appropriatly, stop cancer progression. ... De Grey proposes [that] the only real approach is [to] take specific steps to intervene on a regular basis so that somatic evolution stays in check and we don’t get the unregulated proliferation and invasiveness that is cancer. His WILT approach argues we achieve this by regulating the length of telomeres which are critical to the proliferation process. Carlo Maley says that the WILT approach should work, but the technology is a far way off and it's hard work to go this route. Maley believes that we may be closer on the prophylactic front with by boosting cancer-suppression genes, as in the super p53 approach."

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.

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."

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."

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."

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."

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."

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."

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."



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