Fight Aging! Newsletter, April 14th 2014

April 14th 2014

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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  • More Attention for "Death is Wrong"
  • D-Glucosamine as an Example of Calorie Restriction Mimetic Research
  • Reversal of Hepatocyte Senescence
  • No One Cares About Research Funding
  • SENS Research Foundation Newsletter, April 2014
  • Latest Headlines from Fight Aging!
    • Arguing for More Research into Parabiosis Effects
    • Targeting Cancer With Magnetic Nanoparticles
    • On Body Temperature and Pace of Aging
    • Thymus Regeneration Demonstrated via Increased FOXN1
    • Theorizing on Mitochondria and Iron Homeostasis in Aging
    • Cryonics in Canada
    • Stem Cells Show Promise in Stroke Treatment
    • Sensory Neuron Function and Calorie Restriction Induced Longevity Linked in Nematodes
    • Creation of Functional Tissue Engineered Vaginas
    • Nose Reconstruction With Tissue Engineered Cartilage


I like to see advocates setting forth to create small scale initiatives like the children's book Death is Wrong and the associated fundraiser to distribute copies. At the large scale a broad advocacy movement for a cause in medical research isn't a monolithic thing; it is made up thousands of such efforts, a tapestry of individual who each thought enough of the cause to stand up and do something about it. More of this is always a good thing, and working towards a cure for degenerative aging is the most worthy of causes that I know of.

Donating to the right sort of cutting edge research is one approach, and the one I favor, but equally we have to get out there and persuade more people to do the same. Money has to come from somewhere. There is always a balance between raising research funding to get the job done versus funding the cost of gathering more supporters and thus making it more likely that greater amounts of research funding can be obtained. Research results help to convince more people to fund more research, but there is never enough support in the early crucial stages - the really large amounts of research funding arrive after the most important work is done, as is the case for every trend.

The starting point for large amounts of future funding and rapid progress towards actual, real, working rejuvenation treatments is some mix of research funding and advocacy initiatives today, however. All such efforts should be encouraged, as it is through them that the longevity science community finds its way to a louder voice in the public sphere, a taller soapbox from which to persuade and educate. Aging is a horror, the greatest cause of pain and suffering in this world of ours, and we stand at the verge of being able to do something about it - but only if many more people come to think that this cause has merit and make their own contributions to help out.

Praise for Death is Wrong, a delicious transhumanist book for children

Death is a disease, and hopefully future scientists, perhaps including the young readers of the book, will find a cure. Previous generations thought that death is inevitable, and invented delusional fake philosophies to make death easier to accept. This reaction is understandable - if you can't avoid something, you look for ways to accept it - and explains all usual rhetorical babbling in praise of death: "overpopulation, make room for the young, death is a tool of evolution, boredom after a long life," and the utterly idiotic "death gives meaning to life." The book deconstructs all these fake "arguments" and calls them what they are: understandable but pathetic attempts to rationalize the inevitable.

Provocative strong messages get heard, and teaching children that death will be cured is very provocative in today's dull, defeatist, politically correct cultural climate. I think writing for children forces to keep things clean end simple, without big words and endless caveats, cutting through the noise and getting to the point. Clear, clean, and simple communication focused on the core message, with qualifications and caveats (if they are really needed) in footnotes, is something that transhumanists should practice more, and writing for children is a good way to learn.

Spreading the Word That Death is Wrong

Who could have thought a month ago that an illustrated children's book on indefinite life extension would become a fiercely, passionately discussed phenomenon not just in transhumanist and futurist circles, but on mainstream publications and forums? And yet that is exactly what has happened to Death is Wrong - certainly the most influential and provocative of all of my endeavors to date. I am thrilled that it is precisely my pursuit of this most fundamental and precious goal - preservation of the life of every innocent individual - that has achieved greater public exposure, controversy included, than anything else I have ever done.

Review of "Death is Wrong" by Adam Alonzi

Death can be cured. Let this sink into your brain, not because it is comforting, but because it is true. Even obvious truths will not gain acceptance unless we vigorously campaign against the falsehoods. Death is not something to embrace, and it is not something to ignore. To turn it into a matter of metaphysics or "bioethics" is insulting to those who, by no fault of their own, are burdened by the ailments of old age. There are many extraordinary men and women who could go on working for hundreds of years if their stars were not designed to dim so soon.


While destined to be a deserted sideline of longevity science at some point in the years ahead, research into calorie restriction mimetic drugs is presently in its heyday. Calorie restriction with optimal nutrition slows aging and extends life in near every species tested to date, though the shorter the natural life span of the species the greater the effect. A calorie restricted mouse can live 40% longer in excellent health, but that certainly isn't the case for humans - we'd have noticed an effect that large long ago. This is interesting, because the short-term effects on metabolism and markers of health are similarly large and beneficial in both species. Nonetheless, the consensus in the research community expects the effects of calorie restriction on human life span to be at the most in the ballpark of a 5% increase. The effects on health are much more impressive, however: if calorie restriction were a drug, it would dwarf the sales of any other pharmaceutical created to date, and deservedly so.

So if this is so great, why is it going to be a backwater? Because the objective of a calorie restriction mimetic drug is, as the name suggests, to mimic the metabolic response to calorie restriction - to produce at least some of the same health benefits. A perfect mimetic would result in the same outcome as practicing calorie restriction. But that means a mere boost to health and life that is large in comparison to doing nothing, but is tiny on the scale of what is possible through future medical science. We are entering the era of rejuvenation biotechnology, in which researchers are even today working on the foundations of ways to reverse the cellular and molecular damage that causes degenerative aging. That is the road to indefinite health, completely prevention of age-related disease, and a youth that lasts for as long as you want it to. It won't take much of that for the current fad of drug development aimed at slightly slowing down aging to wither away in favor of the obviously better line of business.

Nonetheless, much - arguably most - of the members of the comparatively small research community interested in treating aging are working away on this backwater to be. It is the mainstream flavor of today, just as the (probably only marginally better) mainstream flavor of tomorrow will involve genetic studies of aging and longevity. The disruption of treating aging as damage and working to repair it is under way with the advent of organizations like the SENS Research Foundation, but has a fair way to go yet before it takes over the mainstream.

The open access paper linked below gives a very good feel for the present state of calorie restriction mimetic research. There are a lot of compounds that seem promising, and researchers are engaged in tying their effects back to the growing knowledge of the puzzle of interrelated proteins and genes that make up the highly flexible operation of metabolism. For most this is the primary goal: not the generation of therapies, but the use of calorie restriction and ways to imperfectly recreate its effects as tools to understand the way in which metabolism determines the pace of aging, all the way down to the most fundamental interactions between proteins in cells. This is a very long-term project. The research community will have effectively cured aging long before the whole intricate dance of its progression is completely understood down to the lowest levels, or at least this will happen if all goes well in the repair strategy field.

All that said, the research into metabolism and aging is interesting and worth reading. It just isn't the road to human longevity in any practical, useful to those of us reading this today sense.

D-Glucosamine supplementation extends life span of nematodes and of ageing mice

D-Glucosamine (GlcN) is being widely used to prevent and treat osteoarthritis in humans and, according to a number of clinical studies, may be effective in this regard. However, mounting evidence suggests that GlcN may be ineffective in ameliorating symptoms and parameters of osteoarthritis. Nevertheless, GlcN has been in long-term use in humans for several decades and induces no relevant side effects aside from occasional allergic reactions.

Short-term administration of high-dose GlcN to model systems or humans acutely impairs glucose metabolism that resembles some of the metabolic features of diabetes mellitus. By contrast, chronic GlcN intake has no detectable influence, or even blood glucose-lowering effects in humans.

Long-term inhibition of glycolysis, by either applying RNA interference (RNAi) to impair expression of glycolytic enzymes, with the application of 2-deoxy-D-glucose (DOG), or by impeding insulin/IGF1 receptor signalling uniformly extends the life span of C. elegans, whereas increased glucose availability reduces nematodal life span. As none of these aforementioned interventions are readily available for use in humans to extend life span, and particularly owing to the fact that DOG unexpectedly shortens life span of rodents, we have now tested whether GlcN could promote healthspan in C. elegans and rodents.

We here find that GlcN inhibits glycolysis to cause an energy deficit that induces mitochondrial biogenesis and alternate fuel use, namely amino-acid oxidation. This is paralleled by an extension of life span in both C. elegans and ageing mice, the latter also showing improved glucose metabolism. These findings implicate that GlcN supplementation may be a versatile approach to delay ageing in humans.

If you dig into the paper, you'll find that life extension in mice is modest, around 10% or so, but pretty consistent judging from the charts. This is for supplementation starting at the two year mark and continuing for another year, by which time only a few mice remained from either group.

For my money an increased knowledge of metabolism and aging is really the only reason to pursue something with such a modest outcome at the dawn of the age of rejuvenation research. The quest for knowledge is a noble thing in and of itself, but don't fool yourself into thinking that this and similar work forms any sort of a road to radical life extension in humans. It does not and cannot. That goal can only come about in the next few decades, soon enough to matter, through growth and development of repair strategies that focus on identifying and repairing the fundamental differences between old tissues and young tissues - a form of research and development that is far, far removed from the paper quoted above.


Researchers are doing far too many things with cells for any one person to know about every single study, or even every category of study. In the past twenty years the doors have opened and the costs dropped to the point at which any laboratory can support numerous separate and adventurous voyages of discovery into cell behavior and biology. Cells are stretched, sliced, grown, transplanted this way and that, genetically engineered, exposed to substances, and so on and so forth, and thousands of these studies are ongoing at any given time.

In among all of this exploration, we should not be surprised to find that some researchers uncover ways to reverse aspects of cellular aging. It is important to remember that cell aging is a different thing altogether from the aging of an organism made up of cells. One affects the other, but it isn't a direct relationship by any means. Cells respond to their circumstances and there is plenty of evidence to suggest that if given the right stimulus some types of cell can remake themselves to a large degree, stripping out damage and unwanted waste to become pristine. We know that this happens somewhere in the sequence of events that leads to embryonic development: parents are old, children are young. We also know that bacteria, hydra, and similar entities can perform much the same operation under some circumstances. This is certainly not something you'd want taking place in your nervous system, however, and the fact that we have complex brains and nervous systems may be a consequence of the fact that our cells don't habitually carry out this sort of dramatic cleansing process, unlike those of some species of lower organism.

There are other less drastic examples, however, such as those associated with the state of cellular senescence in which a cell ceases to divide but doesn't destroy itself. Cells in old tissues become senescent in greater numbers, due to some combination of greater levels of cellular damage and a response to signaling proteins present in the cellular environment. This is most likely an adaptation of an embryonic development process to the suppression of cancer risk in later life. However, it is of decidedly mixed results: less cancer, yes, but senescent cells are generally badly behaved in ways that harm tissue integrity and organ function. We would like to get rid of them as the accumulation of senescent cells is in fact one of the causes of degenerative aging. Removal of these cells by means of targeted destruction seems to be beneficial in those studies attempted to date.

What if we could reverse cellular senescence, however? It is a little early to claim that this is a plausible goal, or that it would cause fewer problems than it solved, but there is some research taking place along these lines. In connection with all of this, the paper linked below outlines the discovery of cells acting to reverse their senescent status in response to circumstances as they are manipulated in a system for growing liver cells known as hepatocytes. This involves the use of genetically engineered immune deficient mice as hosts for transplanted human hepatocyte cells, and one characteristic of this system is that as the human cells grow in number they can be serially transplanted between mice to increase the rate of growth so as to obtain a usefully large amount of cells in a usefully short period of time. It is worth remembering that the research community is not yet at the point of being able to arbitrarily grow every type of cell at the drop of the hat: many lines of research still require complex systems involving laboratory animals in order to investigate cells in a life-like environment. This will change in the years ahead, but it is what it is for now.

Using this system of serial transplants of human hepatocytes between mice, these researchers noticed that the cells responded to transplantation by reversing their senescent status:

Reversal of hepatocyte senescence after continuous in vivo cell proliferation

A better understanding of hepatocyte senescence could be used to treat age-dependent disease processes of the liver. Whether the continuously proliferating hepatocytes could avoid or reverse senescence has not been fully not elucidated yet. We confirmed that the livers of aged mice accumulated senescent and polyploid hepatocytes, which is associated with accumulation of DNA damage and activation of p53-p21 and p16ink4a-pRB pathways.

Induction of multiple rounds continuous cell division is hard to apply in any animal model. Taking advantage of serial hepatocyte transplantation assays in the fumarylacetoacetate hydrolase deficient (Fah-/-) mouse, we studied the senescence of hepatocytes that had undergone continuous cell proliferation over a long time period, up to 12 rounds of serial transplantations.

We demonstrated that the continuously proliferating hepatocytes avoided senescence and always maintained a youthful state. The re-activation of telomerase in hepatocytes after serial transplantation correlated with reversal of senescence. Moreover, senescent hepatocytes harvested from aged mice became rejuvenated upon serial transplantation, with full restoration of proliferative capacity. The same findings were also true for human hepatocytes. After serial transplantation, the high initial proportion of octoploid hepatocytes decreased to match the low level of youthful liver, suggesting that the hepatocyte "ploidy conveyer" is regulated differently during aging and regeneration. The findings of reversal of hepatocyte senescence could enable future studies on liver aging and cell therapy.

You might consider this result in the context of other studies that have shown renewal of stem cell activity when stem cells are moved from old individuals to young individuals, or simply have the protein levels present in an old environment replaced by those of a younger environment. It is a data point and a starting position for further research into whether or not it is useful to attempt to reprogram cells in the body by altering levels of signaling proteins. The initial signs are promising, but there is ever the concern that waking these cells will raise the risk of cancer, or cause other disruptions that may outweigh the benefits.


To a first approximation no-one cares about research funding. No-one cares until it is too late, until their life depends upon a cure or at least a treatment that doesn't yet exist. The vast majority of people are focused on circuses and distractions among the possibilities that presently exist, not on the creation of new possibilities. Just look at the ocean of funding for sports, politics, and war in comparison to the small drops of funding for medical research.

Among the comparatively small class of people who do care about research funding, most of these individuals care because they are in business and the existence of competitors forces them onto the rat wheel of progress. They don't care because they want to produce specific end results, they care because they have to organize research in order to keep up and defend their business. That feels like a rat wheel when you are on the inside, since all of your competitors have wheels of their own and are rarely far behind, tomorrow's board meeting will be much the same as today's regardless of how fast you run, and success on the wheel just means the chance to run again later. From the outside these are the true engines of progress, however, racing ahead to give us ever better products and services - including ever-better medicine.

But this is why we have patient advocacy, in which the small number of people with greater foresight, those who do care about medical research funding because they have looked ahead and understand enough of a field to know what is plausible, try to convince those with lesser foresight of the need for action.

At present research into aging and longevity receives a pittance in funding, private or public, in comparison to any sensible yardstick. People simply don't care to do anything about degenerative aging, and this prevalent attitude is reflected at the large scale in funding levels for various activities. Where there is a will to act and work on ways to treat aging, it is driven by iconoclasts, heretics, and visionaries: the sensible few, not the comfortably conformist many.

Yet it isn't just longevity research in which researchers can bemoan the fact that their field is unjustly the poor cousin in the broader field of medicine, receiving next to nothing in comparison to its great importance. While more than 90% of the Western world suffers and dies due to aging, only a fraction of existing medical research funding goes towards doing anything about this, and even then all existing medical research funding is but a fraction of the funds spent on either (a) idle pastimes, or (b) cleaning up after the consequences of aging. This is the common condition for anyone involved in medical research of any sort, and even the most mainstream of institutions working on diseases of aging can point out that they too are neglected in comparison to their importance:

Alzheimer's Is Expensive, Deadly and Growing. So Where's the Research Money?

"The epidemic is upon us," says Dr. John Trojanowski, co-director of the Center for Neurodegenerative Disease Research and director of the Institute on Aging, both at the University of Pennsylvania School of Medicine. "It's a very difficult thing to say to a patient that there's nothing we have for you, but that is the honest response. There are no disease-modifying therapies for Alzheimer's."

Alzheimer's is one of the costliest chronic diseases to the country. Total costs of caring for Americans with Alzheimer's and other dementias is expected to reach $214 billion this year, with Medicare and Medicaid covering $150 billion and out-of-pocket expenses reaching $36 billion.

Historically, Alzheimer's research has been grossly underfunded. The National Institutes of Health (NIH) dedicated $5.3 billion to cancer research in 2013, nearly $3 billion to HIV/AIDS, $1.2 billion to heart disease and $1 billion to diabetes. Alzheimer's research received just over $500 million.

"I believe that this disease will be the defining medical condition of our generation--hopefully not the next generation," says Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer's Disease Research Center and chair of the Advisory Council for NAPA. "If we don't get on top of it, it will bankrupt the health-care system."

As is the style of the press these days the article above focuses on public funding and its grandstanding political theater rather than the larger and arguably more important body of private research funding. The public funding numbers might seem large, but they are only a fraction of the valuation of the bubblegum industry or any single large sports franchise, of which there are many. But as I said above, to a first approximation no-one cares about research funding. If they did a great many problems would perhaps already be solved.


The SENS Research Foundation is one of the few scientific organizations energetically working on realistic approaches to human rejuvenation treatments, based on repair of the known cellular and molecular damage that causes aging. This is very much a departure from the current mainstream of medicine where researchers largely ignore aging as a cause of disease in favor of trying to patch over age-related conditions in their late stages. As a strategy this is doomed to be an expensive and poor path forward, which is precisely why we need disruptive initiatives like the SENS Research Foundation to shake things up and illustrate the better path ahead. The Foundation funds research where there are roadblocks or a lack of progress, but is as much involved in advocacy, both within the scientific community to convince more researchers to work in this important field, and outside the community in order to sway funding sources and the public at large.

The latest SENS Research Foundation newsletter arrived in my in-box today, along with an announcement that registration is open for a new rejuvenation biotechnology conference that will be held in California later this year.

Registration Now Open For Rejuvenation Biotechnology 2014

Where: Hyatt Regency Santa Clara, Santa Clara, CA
When: August 21 - 23, 2014
To Register:

SENS Research Foundation is pleased to announce that registration is now open for the Rejuvenation Biotechnology 2014 Conference. The conference theme is Emerging Regenerative Medicine Solutions for the Diseases of Aging. The Rejuvenation Biotechnology Conference builds upon novel strategies being pioneered by the Alzheimer's and cancer communities. By convening the foremost leaders from academia, industry, investment, policy, and disease advocacy, SRF seeks to inspire consideration of the wider potential of these strategies and evaluate the feasibility of preventative and combinatorial medicine applications to treat all aging-related diseases.

Confirmed speakers include:

* Richard Barker, CASMI
* Maria Blasco, Spanish National Cancer Research Centre
* George Church, Harvard Medical School
* Aubrey de Grey, SENS Research Foundation
* Caleb Finch, USC Davis School of Gerontology
* Jeanne Loring, Scripps Research Institute
* Stephen Minger, GE Healthcare Life Sciences, UK
* Brock Reeve, Harvard Stem Cell Institute
* Matthias Steger, Hoffmann-La Roche
* Michael West, Biotime, Inc.

Students and researchers are invited to submit poster abstracts for the Rejuvenation Biotechnology Conference Poster Session. Poster submissions will be evaluated by members of the SENS Research Foundation Team. The deadline for poster submissions is July 15, 2014.

We invite everyone in our community to register and participate in this new conference, our first in the US in over 6 years.

As is usually the case, the scientific section of the newsletter is also well worth reading. This time it is an examination of mitochondria and their role in aging:

Question Of The Month #2: Aging and the Limits of Mitochondrial Restoration

Q: Why can't fixing mitochondrial mutations and restoring peak ATP levels in the majority of cells in older people fix everything? I understand there are several classes of accumulated age-related damage like plaque build-up and glycation, which is why it seems like we'd need more than one approach to reverse aging, but if we give cells enough energy, could it be possible that all of it will just take care of itself? In other words, if cells once again have enough energy to perform their jobs to full capacity, couldn't they then carry out functions/mechanisms crucial to getting rid of all the age-related damage? I mean it sounds odd if you think of it using the car analogy: if you give an old car a new battery it's not going to fix other things like rust accumulation or leaky pipes... but because cells all work as a system, I think it's more likely that they'd be able to help control age-related accumulations.

A: While mitochondrial DNA mutations are indeed important to address in the context of a comprehensive rejuvenation strategy like SENS, there are several reasons to think this alone would not be enough to deal with most other forms of aging damage.

First, it's actually not all that clear that the mitochondria in the great majority of an aging person's cells actually suffer much decline in capacity to produce ATP. Certainly many older cells do suffer energy deficits, related to insulin resistance and/or secondary to other age-related metabolic (mal)adaptations - but those are causes unrelated to mitochondrial mutations.

True, the cells whose mitochondria we're most concerned about suffer a pretty drastic reduction in energy production: those are cells that have been taken over by mitochondria harboring large deletions. But remember that such cells constitute a tiny percentage of the cells in the body. If the goal is simply to restore the capacity of the mitochondria in the majority of aging people's cells to produce ATP to levels similar to young people, we're already there.

Also, while individual cells overtaken by mutant mitochondria certainly lack energy, such energy deficits don't do anything to hold back the great majority of the body's cells (since individual cells have their own mitochondrial power supply). Yet they still suffer aging damage. Furthermore, much aging damage accumulates because we lack the means to deal with it, meaning no amount of energy alone can prevent its accumulation.

Third, a lot of aging damage is extracellular, and such damage can't really be addressed in most cases by cells. This is especially true in the case of damage to extracellular matrix (glycation crosslinks and mechanical fatigue of arterial and other elastin lamellae, for instance), where typically there isn't even any ATP available, irrespective of a person's age.

Fourth: remember, we were all young once. At that point, few or none of our cells had been taken over by mutant mitochondrial DNA, and yet even at that point in our lives we were aging. Indeed, this is true of the two examples you cite in your question: we are all born with at least some aging damage, such as fraying of arterial elastin and early atherosclerotic lesions. If youthful mitochondrial energetics were enough to abrogate the accumulation of aging damage, the degenerative process wouldn't get going until a substantial number of our cells were occupied by mutant mitochondria (which, again, arguably doesn't even happen when people reach what are today rather advanced ages).

Most importantly: while it may one day be possible to begin administering rejuvenation therapies to people who are still in their youthful prime, at present we do not have the luxury to do this. Early recipients of rejuvenation biotechnologies will, by and large, be people whose bodies are already riddled with multiple kinds of cellular and molecular aging damage. Even if mitochondria capable of churning out ATP with the alacrity of Usain Bolt in his prime were enough to prevent other forms of aging damage from getting started (and again, the normal course of aging argues strongly otherwise), it seems far less plausible that it would be able to reverse the accumulation of aging lesions in people who have already been suffering such damage for six decades or more of life.

In short: if we are to save the greatest possible number of people from the age-related slide into disease, disability, dependence, dementia, and eventual death, we are going to have to tackle the full spectrum of aging damage that has already riddled their bodies, and obviating mitochondrial mutations seems highly unlikely to achieve this key goal on its own.


Monday, April 7, 2014

In recent years researchers have gained some understanding of how aging diminishes the vital activity of stem cell populations by linking the blood flows of old and young mice, a process called heterochronic parabiosis. It has opened the door to identifying and altering environmental factors that lead to stem cell decline, an approach that doesn't address the underlying damage of aging that causes changes in the levels of chemical signals in tissue, but which may still prove beneficial.

This open access paper argues that parabiosis has a rich history in research and is presently underused as a tool for further investigation:

Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago, yet many of the most devastating diseases of our time are still untreatable. Chronic conditions of age such as cardiovascular disease, diabetes, osteoarthritis or Alzheimer's disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which is characterised by a shared blood supply between two surgically connected animals, may just provide such a transformative experimental paradigm. Although forgotten and shunned now in many countries, it has contributed to major breakthroughs in tumour biology, endocrinology and transplantation research in the past century.

Interestingly, recent studies from the United States and Britain are reporting stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice, indicating a possible revival of this paradigm. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited to allow its use in biomedical research.

Monday, April 7, 2014

The future of cancer treatments involves the targeted delivery of cell-killing mechanisms to cancer cells. As a strategy this offers the potential to minimize side-effects to far below the levels of present day established treatments such as chemotherapy and radiotherapy. There are many ways to kill cells while causing minimal effects to surrounding tissues, assuming a selective means of delivery to specific cells, and here researchers improve upon the use of nanoparticles as the mechanism of destruction:

Using magnetically controlled nanoparticles to force tumour cells to 'self-destruct' sounds like science fiction, but could be a future part of cancer treatment. In brief, the technique involves getting the nanoparticles into a tumour cell, where they bind to lysosomes, the units in the cell that perform 'cleaning patrols'. The lysosomes have the ability to break down foreign substances that have entered a cell. They can also break down the entire cell through a process known as 'controlled cell death', a type of destruction where damaged cells dissolve themselves.

The researchers have used nanoparticles of iron oxide that have been treated with a special form of magnetism. Once the particles are inside the cancer cells, the cells are exposed to a magnetic field, and the nanoparticles begin to rotate in a way that causes the lysosomes to start destroying the cells.

The research group [is] not the first to try and treat cancer using supermagnetic nanoparticles. However, previous attempts have focused on using the magnetic field to create heat that kills the cancer cells. The problem with this is that the heat can cause inflammation that risks harming surrounding, healthy tissue. The new method, on the other hand, in which the rotation of the magnetic nanoparticles can be controlled, only affects the tumour cells that the nanoparticles have entered.

Tuesday, April 8, 2014

Here is a very brief high level overview of some of what is known about the relationship between body temperature and longevity in mammals. As for many aspects of our biology, researchers have pulled out associations from the data but questions of cause, effect, and mechanisms involved are all very much up for debate.

Some studies show a correlation between lower body temperatures and greater longevity, though there is no proof of a cause-and-effect relationship in humans. The first such major study in warmblooded animals was a 2006 experiment involving mice at the Scripps Research Institute. Genetically engineered mice with extra-sensitive temperature control switches in the hypothalamus were raised with core body temperatures just a fraction of a degree cooler than those of their litter mates; caloric intake was the same. The researchers found the median life span was 12 percent greater in the cooler males, 20 percent greater in the females.

As for humans, a large study published in 2011 compared the ages and body temperatures of 18,630 people from 20 to 98 years old who had oral temperature readings as part of a standardized health appraisal at a health maintenance organization. Mean temperature decreased with age, with a difference of 0.3 degrees Fahrenheit between the oldest and youngest groups, even after controlling for sex, body mass index and white-blood-cell count.

"The results are consistent with low body temperature as a biomarker for longevity," the researchers concluded. As for possible reasons for such results, they suggested identifying genetic influences on body temperature and examining the effect of body temperature on multiple cellular processes.

Tuesday, April 8, 2014

Researchers have demonstrated that they can produce a functionally youthful thymus in old mice by increasing levels of a single protein. There have been suggestions that such an approach might be made to work - tweak signal protein levels such that they are similar to those that existed during the early development of the thymus - but I have to admit that I wasn't expecting anything so impressive at this stage. It is an important advance if verified in other labs, as regeneration of the thymus is one of the methods by which the failing immune system in older people could be restored to greater function, at least partially ameliorating this one aspect of frailty in the aged.

One of the issues that contributes to the age-related decline of the immune system is a comparative lack of a supply of fresh immune cells, those capable of tackling new threats. The thymus, where these cells mature, has evolved to pump out a large supply of immune cells in childhood but it then atrophies soon afterwards - a process known as thymic involution. The adult thymus is a shadow of its former self and delivers only a trickle of new immune cells.

The SENS Research Foundation has been funding work on tissue engineering of the thymus, as a part of a portfolio of work on the foundations of human rejuvenation, and I'm sure that this will be a welcome addition to the list of potential strategies for thymic regeneration:

British scientists have for the first time used regenerative medicine to fully restore an organ in a living animal, a discovery they say may pave the way for similar techniques to be used in humans in future. The [team] rebuilt the thymus - an organ central to the immune system and found in front of the heart - of very old mice by reactivating a natural mechanism that gets shut down with age. The regenerated thymus was not only similar in structure and genetic detail to one in a young mouse, the scientists said, but was also able to function again, with the treated mice beginning to make more T-cells - a type of white blood cell key to fighting infections.

[The researchers] targeted a part of the process by which the thymus degenerates - a protein called FOXN1 that helps control how key genes in the thymus are switched on. They used genetically modified mice to enable them to increase levels of this protein using chemical signals. By doing so, they managed to instruct immature cells in the thymus - similar to stem cells - to rebuild the organ in the older mice.

Wednesday, April 9, 2014

Here researchers theorize on connections between some measurable aspects of aging, those being mitochondrial damage and the role of iron in metabolic processes. As is always the case this sort of search for connections is bedeviled by the fact that aging is a global process: all sorts of changes happen in parallel, and establishing cause and effect, or even just linkage rather than mere association, is ever a challenge.

Free (labile or chelatable) iron is extremely redox-active and only represents a small fraction of the total mitochondrial iron population. Several studies have shown that the proportion of free iron increases with age, leading to increased Fenton chemistry in later life. It is not clear why free iron accumulates in mitochondria, but it does so in parallel with an inability to degrade and recycle damaged proteins that causes loss of mitochondrial protein homeostasis (proteostasis). The increase in oxidative damage that has been shown to occur with age might be explained by these two processes.

While this accumulation of oxidative damage has often been cited as causative to ageing there are examples of model organisms that possess high levels of oxidative damage throughout their lives with no effect on lifespan. Interestingly, these same animals are characterised by an outstanding ability to maintain correct proteostasis during their entire life. Reactive oxygen species can damage critical components of the iron homeostasis machinery, while the efficacy of mitochondrial quality control mechanisms will determine how detrimental that damage is.

Here we review the interplay between iron and organellar quality control in mitochondrial dysfunction and we suggest that a decline in mitochondrial proteostasis with age leaves iron homeostasis (where several key stages are thought to be dependent on proteostasis machinery) vulnerable to oxidative damage and other age-related stress factors. This will have severe consequences for the electron transport chain and TCA cycle (among other processes) where several components are acutely dependent on correct assembly, insertion and maintenance of iron-sulphur clusters, leading to energetic crisis and death.

Wednesday, April 9, 2014

Cryonics is the low-temperature preservation of at least the brain immediately following death, in order to preserve the structures that encode the data of the mind. For those who will age to death prior to the advent of rejuvenation treatments in the decades ahead this is the only shot at a longer life in the future. A society with the technologies necessary to restore a cryopreserved individual to life is a society that should have no issues with regenerating a new body and repairing the damage of aging.

Cryonics remains a small industry, not all that much larger than it was in the 1970s when early amateur efforts transitioned into more professional non-profit organizations. We live in a world in which it has long been technologically feasible to prevent the absolute loss to oblivion of a majority of the people who die in any given year, yet only a vanishingly small fraction of the population seem to have any interest in this goal. The rest march in lock-step to die without making any meaningful attempts to do something about it.

Here is a short interview with the president of the Cryonics Society of Canada:

The Alcor Life Extension Foundation, and the Cryonics Institute are the two main organizations in North America that offer cryopreservation and long-term storage. They have different business structures and very different prices. KrioRus in Russia is a third option. It is the first, and currently only, cryonics company in Europe or Asia.

Each organization has a process for membership that includes the requisite paperwork. Most people that sign up opt to have their services funded through a life insurance policy. The organizations can best advise you on which insurance companies are most ideal for this purpose. You will likely pay a small amount in membership dues, and then upon pronouncement, your insurance policy (or alternate means of funding) will be applied to your immediate needs.

Cryonics is not illegal in Canada. It is regarded as an end-of-life choice, and there are no legal barriers to performing this service. The only exception is in British Columbia, which passed a law several years ago forbidding the marketing of cryonics services. Members in B.C. have been successfully cryopreserved, though, within full observation of the law.

Cryonics patients are legally dead, so although there are no specific laws which deal with cryopreservation, cryonics organizations handle patients while observing the laws governing anatomical donations of a body to science and the laws that govern the funeral service. Transportation of patients is done in collaboration with a licensed funeral director, after a person has been legally pronounced and certified as deceased by the appropriate medical provider. By keeping the wishes of the patient known, and the process transparent, legal authorities generally do not take issue with the practice.

Mainstream science has historically been skeptical of cryonics, as it is a process that cannot yet be reversed by modern technology. There has been a shift, though, in recent years, in the mainstream, where cryonics has been viewed less and less like science fiction and more like a plausible near-future advancement. How cryonicists respond is quite varied. The Cryonics Society of Canada exists to try to educate the public about cryonics and to advocate for its members. Some members are very vocal and positive about their involvement. Others prefer to keep the matter private.

Thursday, April 10, 2014

The research community continues to validate the benefits resulting from comparatively simple first generation stem cell transplants, of the sort that have been available via medical tourism for a decade:

In an analysis of published research, [researchers] identified 46 studies that examined the use of mesenchymal stromal cells - a type of multipotent adult stem cells mostly processed from bone marrow - in animal models of stroke. They found MSCs to be significantly better than control therapy in 44 of the studies. Importantly, the effects of these cells on functional recovery were robust regardless of the dosage, the time the MSCs were administered relative to stroke onset or the method of administration. (The cells helped even if given a month after the event and whether introduced directly into the brain or injected via a blood vessel.)

MSCs do not differentiate into neural cells. Normally, they transform into a variety of cell types, such as bone, cartilage and fat cells. The cells are attracted to injury sites and, in response to signals released by these damaged areas, begin releasing a wide range of molecules. In this way, MSCs orchestrate numerous activities: blood vessel creation to enhance circulation, protection of cells starting to die, growth of brain cells, etc. At the same time, when MSCs are able to reach the bloodstream, they settle in parts of the body that control the immune system and foster an environment more conducive to brain repair.

"Stroke remains a major cause of disability, and we are encouraged that the preclinical evidence shows [MSCs'] efficacy with ischemic stroke. MSCs are of particular interest because they come from bone marrow, which is readily available, and are relatively easy to culture. In addition, they already have demonstrated value when used to treat other human diseases."

Thursday, April 10, 2014

Researchers here theorize that alterations to neurons are an important part of the metabolic improvements and enhanced longevity produced by calorie restriction, at least in nematode worms:

Progressive neuronal deterioration accompanied by sensory functions decline is typically observed during aging. On the other hand, structural or functional alterations of specific sensory neurons extend lifespan in the nematode C. elegans. Hormesis is a phenomenon by which the body benefits from moderate stress of various kinds which at high doses are harmful. Several studies indicate that different stressors can hormetically extend lifespan in C. elegans and suggest that hormetic effects could be exploited as a strategy to slow down aging and the development of age-associated (neuronal) diseases in humans. Mitochondria play a central role in the aging process and hormetic-like bimodal dose-response effects on C. elegans lifespan have been observed following different levels of mitochondrial stress.

Here we tested the hypothesis that mitochondrial stress may hormetically extend C. elegans lifespan through subtle neuronal alterations. In support of our hypothesis we find that life-lengthening dose of mitochondrial stress reduces the functionality of a subset of ciliated sensory neurons in young animals. Notably, the same pro-longevity mitochondrial treatments rescue the sensory deficits in old animals. We also show that mitochondrial stress extends C. elegans lifespan acting in part through genes required for the functionality of those neurons. To our knowledge this is the first study describing a direct causal connection between sensory neuron dysfunction and extended longevity following mitochondrial stress. Our work supports the potential anti-aging effect of neuronal hormesis and open interesting possibility for the development of therapeutic strategy for age-associated neurodegenerative disorders.

Friday, April 11, 2014

In terms of complexity, this seems on a par with generating a new trachea or esophagus, both goals that were achieved in recent years:

Four young women born with abnormal or missing vaginas were implanted with lab-grown versions made from their own cells, the latest success in creating replacement organs that have so far included tracheas, bladders and urethras. Follow-up tests show the new vaginas are indistinguishable from the women's own tissue and have grown in size as the young women, who got the implants as teens, matured. All four of the women are now sexually active and report normal vaginal function. Two of the four, who were born with a working uterus but no vagina, now menstruate normally.

The pilot study is the first to show that vaginal organs custom-built in the lab using patients' own cells can be successfully used in humans, offering a new option for women who need reconstructive surgeries. All four of the women in the study were born with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a rare genetic condition in which the vagina and uterus are underdeveloped or absent. Conventional treatment generally involves the use of grafts made from intestinal tissue or from skin, but both tissues have drawbacks.

The researchers started off by collecting a small amount of cells from genital tissue and grew two types of cells in the lab: muscle cells and epithelial cells, a type of cell that lines body cavities. About four weeks later, the team started applying layers of the cells onto a scaffold made of collagen, a material that can be absorbed by the body. They then shaped the organ to fit each patient's anatomy, and placed it in an incubator. A week later, the team created a cavity in the body and surgically attached the vaginal implants to existing reproductive organs. Once implanted, nerves and blood vessels formed to feed the new organ, and new cells eventually replaced the scaffolding as it was absorbed by the body.

Friday, April 11, 2014

Cartilage is a surprisingly complex tissue. While researchers are making progress in growing cartilage from a patient's own cells, they have yet to reliably and fully reproduce all of the mechanical properties of the real thing. Fortunately this is less of an issue in the nose than, say, in the knee, as you aren't resting the weight of your body on your nose:

A research team [has] reported that nasal reconstruction using engineered cartilage is possible. They used a method called tissue engineering where cartilage is grown from patients' own cells. This new technique was applied on five patients, aged 76 to 88 years, with severe defects on their nose after skin cancer surgery. One year after the reconstruction, all five patients were satisfied with their ability to breathe as well as with the cosmetic appearance of their nose. None of them reported any side effects.

The type of non-melanoma skin cancer investigated in this study is most common on the nose [because] of its cumulative exposure to sunlight. To remove the tumor completely, surgeons often have to cut away parts of cartilage as well. Usually, grafts for reconstruction are taken from the nasal septum, the ear or the ribs and used to functionally reconstruct the nose. However, this procedure is very invasive, painful and can, due to the additional surgery, lead to complications at the site of the excision.

[Researchers have] now developed an alternative approach using engineered cartilage tissue grown from cells of the patients' nasal septum. They extracted a small biopsy, isolated the cartilage cells (chondrocytes) and multiplied them. The expanded cells were seeded onto a collagen membrane and cultured for two additional weeks, generating cartilage 40 times the size of the original biopsy. The engineered grafts were then shaped according to the defect on the nostril and implanted.


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