Longevity Meme Newsletter, June 14 2010

June 14 2010

The Longevity Meme 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 the Longevity Meme.



- Summits on Open Science
- Tomorrow's Artificial Immune Systems
- New Demographic Examinations of Longevity
- Discussion
- Latest Healthy Life Extension Headlines


The h+ Summit on citizen scientists took place this past weekend, and coming up next month is the Open Science Summit:


"But why should we folk interested in engineered longevity spend much - or any - time following or helping support the open biotechnology movement? I think that the most obvious reason stems from the analogy to the open source software development movement. If you look at the software infrastructure of the present day internet, vast swathes of it are open source, its breadth and quality only made possible by the gift economy that takes shape in unfettered collaborative marketplaces of this nature. A very large fraction of all new innovation on the web now builds on top of open source infrastructure, for example.

"Low cost, high quality tools are the necessary precursors for a large community of skilled amateurs to arise in any field. It happened for software development, and we all benefit greatly from the results of that process. I would like to see it happen in the life sciences as well, because the only thing better than thousands of people advocating for engineered longevity is thousands of advocates who can also step in, do the work, and help to get the job done. Not all biotechnology is rocket science: a great many useful and necessary tasks in any project can be accomplished by undergraduate students - or anyone who has put in a few months of evening reading and practice."

In short, open science and garage biotechnology will lead to faster progress in the areas we care about - and we all want to see that happen.


In the future, our immune systems will be augmented by adaptive nanoscale machinery, rendering us largely immune to disease and cancer. This might seem far from the here and now, but in fact the first foundations of this technology are already emerging from the laboratory:


"For example, it won't be long before clinics can assemble massive doses of artificial antibodies to order and then infuse them into your body. Antibodies are the immune system's weapons, molecules tailored to a specific threat that either directly kill attackers or flag them for ingestion and destruction by white blood cells. An infusion of antibodies produced in the clinic could be vastly larger than what the body is capable of producing on its own, overwhelming an assault.

"Using plastic nanoparticles just 1/50,000th the width of a human hair, [researchers have] created plastic antibodies that successfully function in the bloodstream of living animals to identify and fight a variety of antigens. ... Researchers could tailor a variety of these nanoparticles for use in just about any case where the body relies on antibodies for to fight off threats. That's a lot of cases, opening the door to a synthetic immune booster that could potentially be used to treat myriad allergies, illnesses and infections."

The failing immune system is an important component of age-related frailty. The ideal solution is to repair the damage and rejuvenate the immune system to youthful levels of function, either by destroying malfunctioning immune cells en masse or restoring the thymus:


Replacing the functions of the immune system one by one with the use of synthetic antibodies is likely to be well worth the effort, however: imagine a world in which every immunological threat to an elderly body could be quickly countered with a trip to the clinic and a low-cost infusion of antibodies. That future is not so far away at all.


Counting heads can be a surprisingly powerful tool in the hands of a statistician. Two interesting new findings have been made recently by processing the databases built in demographic studies of human longevity:


"As I'm sure you're all aware by now, human life expectancy for both young and old in the most developed regions of the world is slowly increasing, and this has been the case for some time. As medical technology advances and our wealth grows, we benefit in ways that lead to less biochemical damage to the complex machinery of our body accumulated over the course of a lifetime - and thus a greater likelihood of living longer.

"The ongoing increase in life expectancy in developed countries is associated with changes in the shape of the survival curve. These changes can be characterized by two main, distinct components: (i) the decline in premature mortality, i.e., the concentration of deaths around some high value of the mean age at death, also termed rectangularization of the survival curve; and (ii) the increase of this mean age at death, i.e., longevity, which directly reflects the reduction of mortality at advanced ages. Several recent observations suggest that both mechanisms are simultaneously taking place. ... We illustrate the method with the evolution of the Swiss mortality data between 1876 and 2006. Using our approach, we are able to say that the increase in longevity and rectangularization explain each about 50% of the secular increase of life expectancy."


"For the purposes of his work into aging and longevity, researcher Michael Rose defines the condition of mortality as being a rising risk of death as time goes on. This is what we see in the world we know: the older a person, a pet, a plant becomes, the more likely it is to die in any given period of time. Immortality, it then follows, is the state of being in which the risk of death does not rise with advancing time.

"As it turns out, our intuitions about the way in which aging and risk of death progress do not accurately reflect what happens in very late life - for those who live much longer than the average. Rose demonstrated that very old flies no longer suffer an increasing risk of death; even though the actual mortality rate is high, it stops growing. These are immortal flies by his definition. I now see that recently published demographic work claims to find the immortality plateau in human supercentenarians."

This result should perhaps not be surprising: we might expect late life immortality in this sense to be a universal condition experienced by any complex system made up of many redundant parts. You might look at the reliability theory of aging and longevity for further insight into thinking about aging in this way:



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!




Here is a dense scientific post from the SENS Foundation that might be better read back to front, starting with the research partnership announcement at the end. Some fraction of degenerative aging is caused by an accumulation of various forms of amyloids between cells, probably the best known of which is that involved in Alzheimer's disease. One goal for the Strategies for Engineered Negligible Senescence (SENS) approach to aging is to establish a general technology platform that can be used to remove any form of amyloid: "In late 2008, we reviewed then-unpublished work by Dr. Mark Pepys, who was working on an ambitious project anticipated to allow for the disaggregation of nearly all disease-associated amyloids. ... I am therefore delighted to have the privilege to be given permission [to] make the first public announcement that the Supercentenarian Research Foundation has recently helped to facilitate a collaboration between researchers already working in amyloid diseases, to develop antibodies to cleave aggregated wild-type and mutant transthyretin - the form responsible for senile cardiac amyloidosis (a prevalent, but not exclusive, cardiac amyloidosis in supercentenarians)."

Via EurekAlert!: "A team of researchers has developed a method to produce cells that kill tumour cells in the lab and prevent tumours forming in mouse models of cancer. ... In this research, T cells were transformed into cells similar to another type, Natural Killer (NK) cells, which commonly act against viruses and cancer cells. ... We had shown that a gene called Bcl11b was essential for normal development of immune system cells - and of particular interest in the development of T cells. Here we can see the fruits of that work: we show, for the first time, that we can modify the developmental fate of immune system cells to produce a novel type that - if we can see the same effect in humans - could be of enormous value in cancer treatment. ... the Bcl11b gene was active only in T cells in the immune system and that its activity was needed at the earliest stages of production of T cells. When the team knocked out the Bcl11b gene, the mice produced no T cells. ... Remarkably, the mice lacking the Bcl11b gene produced a new type of immune system cell - the Induced T to Natural Killer cells. This is the first time we have seen these cells ... Even more important, we can see that these reprogrammed killer cells can attack cancer cells, whether in test tubes or in mouse models. ... The ITNK cells killed melanoma and lymphoma cells in experiment in test tubes and were much more efficient than unmodified Natural Killer cells in the mouse and in human."

WHY AGING RESEARCH? (June 10 2010)
From In Search of Enlightenment: "A person’s interest in remaining healthy and alive does not evaporate as the number of birthday candles they accumulate increases. The aged, like the young, have an interest in remaining healthy and vigorous for as long as possible. When a person over age 65 is murdered or killed in a car accident we conceive of these events as constituting a serious harm. We believe that there is a moral duty to prevent these harms from being realized, if it is possible to do so. Whether these harms come from an external source that we can easily perceive (such as a criminal wielding a gun or a speeding car) or from complex biological processes that are internal to our biology is irrelevant to the stringency of the moral duty to prevent harm. ... the general affluence of a country, as well as its natural resources, profoundly influences the quality of sanitation it can offer its citizens. But in the case of developing an antiaging pill to protect against chronic disease, there is good reason to believe that many of these obstacles will be less of a challenge. Unlike sanitation, the main costs associated with the development of an antiaging pill will most likely be with research and development, rather than the manufacture and dispersion of such a pill. So I believe there is good reason to be optimistic that such an antiaging intervention could be enjoyed by most of the world’s population in a relatively short time from when it is first developed."

A low-cost source of stem cells can generate diseased tissue for study in the laboratory, a use that is probably just as important at the present time as regenerative medicine: researchers "have for the first time differentiated human stem cells to become heart cells with cardiomyopathy, a condition in which the heart muscle cells are abnormal. The discovery will allow scientists to learn how those heart cells become diseased and from there, they can begin developing drug therapies to stop the disease from occurring or progressing. ... [Researchers] took patient skin cells and reprogrammed them to become pluripotent stem cells. Such cells can then develop into almost any type of cell in the human body. The researchers then created heart cells that had characteristics of hypertrophic cardiomyopathy. ... We knew there was potential in using pluripotent stem cells from people with genetic disorders to develop diseases in vitro, but our study is the first to successfully create abnormal heart cells. Now that we have developed these cells, we can study why they become enlarged and develop treatments to prevent them from overgrowing."

Maria Konovalenko on the study of the often large life span differences between similar species - or rather the lack of such research work in comparison to other fields of life science: "Here's this quite simple idea: to take two species similar in size and basic biology, but having a substantial difference in longevity, and figure out what's the reason for this difference. What are the distinctions in the mechanisms of aging and stress resistance? It's desirable to carry out this work in various species. However, not a lot of people are excited about this simple idea. Even the genome of the famous naked mole rat has not been sequenced yet, although many people believe it's got 'negligible' senescence. For now all that we have is negligible funding of evolutionary-comparative biology of aging. Moreover, previously obtained results are put into cold storage. ... And here comes the main question in biogerontology. Why is the research into the fundamental mechanisms of aging so scarcely funded?" Aging and longevity research in general receives very little funding and attention in comparison to its importance to the future of human health. This state of affairs is slowly changing, but not fast enough for my liking.

Via Newswise: "Why all the attention on TOR? TOR (target of rapamycin) is a key nutrient-sensing catalytic enzyme that evolution has conserved among every plant and animal species that has cells containing a nucleus. TOR mediates the connection between nutrients in the environment to the growth and metabolism of the organism. Studies in flies, worms, yeast and mice support the notion that the TOR signaling network also plays a pivotal role in regulating the aging process. When TOR signaling is reduced, either through genetic manipulation or via the use of drugs, the organism presumes there are reduced nutrients in its environment and goes into a 'survival' mode similar to that seen in dietary restriction, which has been shown to extend lifespan and slow the onset of certain age-related diseases. ... it remains to be seen which downstream effectors of TOR are key drivers of longevity and which ones elicit only minor effects. In addition to simply extending lifespan, research on the protective effects of TOR is likely to identify which age-related diseases can be slowed by inhibition of the TOR pathway."

From Depressed Metabolism, a look at the folk who are trying to ensure that cryonics patients can preserve their resources as well as the fine structure of their brains: "On the weekend of April 23-25 I attended a meeting of the cryonics Asset Preservation Group held [near] Gloucester, Massachusetts. I will try to give a few brief summaries without going into detail about every presentation. ... A central problem for cryonicists wanting revival trusts is that Cryopreserved Persons (CPs) are legally dead and are not ascertainable beneficiaries under trust law. My solution to this problem has been to have cryonics organizations (rather than the legal system) recognize the reanimated CP as the beneficiary. But finding the right cryonics organization to do this is not always easy. ... the best presentation at this meeting of the Asset Preservation Group was the one on 'Personal Revival Trusts' by Igor Levenberg. I have been working with the thorny problems associated with cryonics reanimation trusts for years and I have never seen such careful and persuasive legal analyses."

From Singularity Hub: "In order to work in the human body, an artificial cornea has to meet some rather stringent requirements. First, it has to bond to the human eye around its edge, but stay unclouded by cells in its center. To that end, [researchers] took a widely used opthalmological polymer (found often in intraocular lenses) and adapted it with other special polymers around the edges. Combined with the application of a growth factor protein, the modified edge promoted cell growth around the periphery of the implant and secured it in place using the body's own cells. The center of the artificial cornea, however, does not promote cell growth and remains clear so that it can be seen through. The artificial cornea also has to move freely with the eyelid and balance moisture on its faces. The polymer [researchers] chose is hydrophobic, allowing tears to lubricate the surface and provide the correct moisture on both of its sides. ... The artificial cornea has passed clinical trials and is ready to see expanded use in patients this year."

Researchers are turning up new longevity genes at a fair rate these days, and this latest discovery is illustrative of the methods used - start with what you know, and compare and contrast: "A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway."

Accelerated aging conditions may result from individual aspects of "normal" aging run wild and out of control. This means we can potentially learn more about those mechanisms. For example: "a gene shown to play a role in the aging process appears to play a role in the regulation of the differentiation of embryonic stem cells. ... researchers identified a protein interaction that controls the silencing of Oct4, a key transcription factor that is critical to ensuring that embryonic stem cells remain pluripotent. The protein, WRNp, is the product of a gene associated with Werner syndrome, an autosomal recessive disorder hallmarked by premature aging. ... We showed that the depletion of WRNp blocked the recruitment of Dnmt3b to the Oct4 promoter, and resulted in reduced methylation. The reduced DNA methylation was associated with continued Oct4 expression, which resulted in attenuated differentiation. ... These results reveal a novel function of WRNp, and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation. Our data support the emerging hypothesis that attenuated stem cell differentiation is involved in aging. This lack of differentiated cells may contribute to failure to maintain organ or tissue function in the later stages of life."



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