Fight Aging! Newsletter, April 29th 2013

April 29th 2013

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!



- Three and a Half Ways to Cure Cancer
- More Data on Granulocyte Transplant Cancer Therapies
- US Medicine: Death by Command and Control Regulation
- Recent Calorie Restriction Research
- Discussion
- Latest Headlines from Fight Aging!
    - Joining the Dots in Genetic Parkinson's Disease
    - Considering the Electron Transport Chain in Aging
    - Measures of Mitochondrial DNA Damage Lower in Long-Lived Mice
    - Small Amounts of Bioprinted Liver Tissue from Organovo
    - Regenerating Articular Cartilage in Rabbits
    - Targeting Cancer With Radioactive Bacteria
    - Some Preliminary Findings From CALERIE
    - 2013 CR Society Conference, June 5th in California
    - Size and Aging From a Programmed Perspective
    - Study Suggests Dementia Risk Declining


Today's topic is the cure for cancer, something a grail in medicine. It will be challenging to produce, but I think that the difficulty is presently overestimated by much of the public and those in the mainstream of the research community. The reasons for this are understandable: the past half century of cancer research is a story of continually discovered ever greater complexity in cancer biology. It is the sheer exuberant variation in cancer - between types, between tissues, between individuals, and even between tumors in an individual - that makes it such a daunting foe. Every cancer is an evolving mess of broken cells with its own character and biochemical quirks.

We stand now in the early stages of a revolution in biotechnology, however, and the rapidly expanding capabilities that brings to the research community are beginning to reveal that, for all their variety, cancers do have at least some shared characteristics and shared vulnerabilities. It is the commonalities in cancer, things that are emerging now and would have been exceedingly expensive to discover and exploit even a mere twenty years past, that will act as a foundation for the coming generation of effective cancer therapies. In that spirit, I offer you three and a half ways to cure cancer, outlined very briefly below:

1) WILT, whole-body interdiction of lengthening of telomeres

WILT is my least favorite cure for cancer, but it is nonetheless hard to argue that it isn't in fact the ultimate cure for cancer. Cancers absolutely depend upon ways to lengthen telomeres, the protective caps at the end of chromosomes that shorten with each cell division, putting a limit on the life span of ordinary cells. A cell with little left of its telomeres stops dividing, destroys itself, or becomes senescent - and thus not much use as a cancer cell. Telomeres are lengthened by the activities of the telomerase enzyme and the mechanisms imaginatively known as alternative lengthening of telomeres (ALT), both of which are abused by all cancers in order to create unfettered growth.

Disable telomerase and the genes for ALT in a human, and the result will most likely be a human who cannot suffer cancer. There is a reason this is my least favorite approach however, and that is that your stem cell populations require the ability to lengthen telomeres in order to continue to maintain your tissues over the long term. A person who underwent a hypothetical WILT treatment would need stem cell transplants or a similar way to refresh all of the different stem cell populations of the body - and there are many - every decade at least. WILT means exchanging the threat of cancer for an arguably greater dependency on medical technology.

Research into WILT is currently funded to a modest degree by the SENS Research Foundation under the OncoSENS program, with a focus on establishing a a sufficient understanding of ALT to determine the best and most comprehensive way to disrupt its mechanisms.

2) LIFT/GIFT, leukocyte/granulocyte transfusions

Somewhere out there, someone possesses immune cells (the white blood cells called leukocytes or granulocytes) that can kill your cancer. You might consider this approach to immune therapy as being analogous to first generation stem cell therapies that are presently available in many parts of the world: take someone else's immune cells, grow them in culture, and then transplant large numbers of them into your body, where they work to destroy cancer. This methodology has been shown to produce exceedingly impressive results in mice, such as entire lineages of cancer-resistance mice, but it isn't known why exactly it works so well - which makes it hard to proceed to clinical applications in the US, where a full scientific understanding of the mechanisms involved is generally required.

A couple of startups are presently working in this area, such as ImmunePath (probably) and Munogenics, with little funding and slow progress, so far as I'm aware. There is also a small ongoing clinical trial in Florida that looks like it'll wrap up later this year.

This is exactly the sort of application of cell therapies that should do well in the medical tourism arena, and indeed is appearing as an option in some overseas clinics. It is easy enough to implement that any group that can presently carry out stem cell transplants should also be able to manage immune cell transplants. More publicity, signs of progress in obtaining human results, and greater funding for trials would go a long way towards speeding the spread of this therapy and this determining whether the results in mice continue to translate well into humans.

3) Targeted cell killing technology, plus the search for commonalities in cancer

Modular targeted cell killing technology platforms with a slot for a sensing system are well in hand in the lab, and are a big part of why the next generation of cancer therapies will be far more effective and far less traumatic than chemotherapy. A great variety of such systems are presently under development: nanoparticles such as gold rods that can be heated by radiation; nanoparticles such as dendrimers that carry motes of chemotherapy drugs; nanoparticles that carry an RNA interference payload; engineered viruses; engineered bacteria; trained immune cells; and so forth.

The commonality here is that all of these systems are designed to destroy specific cells with minimal damage to surrounding cells - all that is needed are mechanisms to ensure that these cell-killers only target cancer cells. This largely means discovering suitable markers on a cell surface: specific proteins that differentiate cancer cells by the degree to which they are present, and which are sufficiently general to appear in a sizable population of patients or many types of cancer.

The big uncertainty here is whether or not researchers will find targets shared by many cancers that are sufficiently discriminating to allow enough preferential targeting of cancer cells. It's possible to layer multiple poorly discriminating targets to get a highly discriminating system, however, and there are promising signs of late on this front. You might look at trials involving therapies targeting CD47, for example, which appears on most cancers per the latest research.

If there are enough markers like CD47 out there, then it should be possible to build a comparatively small suite of general cancer therapies that will kill 80% of cancers at any stage, metastatic or not, with minimal side effects. At this point in the development of medicine even twenty different loads for the same basic system to effectively tackle 80% of all cancers looks like a very good thing - and very plausible too, if the process of discovering cancer commonalities keeps going the way it is. All that is needed is one kill mechanism and a delivery platform modular enough to accept the different sensor mechanisms while still being manufacturable at low cost, such as through the use of dendrimers or viruses.

3.5) The mechanisms used by naked or blind mole rats

Naked mole rats don't get cancer, and it appears the same is true of blind mole rats, but for different reasons. Present understanding of the evolved mechanisms by which these animals manage to stay cancer-free for the several decades of their life spans, even while living in an environment that produces a tremendous amount of cellular damage, is advanced enough to have a sensible discussion on how to recreate it in humans.

This really only counts as half a potential cancer cure, however. It does seem to grant cancer immunity, or as near to it as counts, but it is a big question mark as to how hard it will be to safely have our cells start to behave in the same way as those of a mole-rat - even only temporarily. In the case of naked mole rats, the mechanism in question involves the genes p16 and p27, which suggests that it's something that could be accomplished via gene therapy, but much remains to be done in order to find out how much work there is here.

So this is certainly as intrusive a proposal as WILT, i.e. we're talking about altering human metabolism and genetic programming, but far less is known regarding how best to move forward with this strategy. Still, it is probably the case that more researchers are working on it than are in the case of WILT - the cancer community is large and well funded, and the study of mole rats is well recognized these days.


I mentioned GIFT/LIFT, the immune cell transplant approach to cancer therapy in a short list of research that might lead to cancer cures. This line of research derives from the fortuitous discovery of a cancer-immune lineage of laboratory mice, followed by the finding that this immunity is transferable via transplant of granulocyte or other forms of leukocyte immune cells.

This discovery raises the possibility that effective cancer treatments can be established by finding donors with appropriately equipped immune cells and then transplanting those cells into patients, even in advance of a complete understanding of how this all works. That complete understanding might enable an effective cure for cancer therapy based on altering a patient's own immune cells, or a much more reliable way to determine useful donors, but it'll take much longer to get to that point, possibly decades. Thus there is considerable incentive to take the shortcut if there's one to be had, in the same way as first generation stem cell transplant therapies continue to be established usefully far in advance of the complete understanding of how they work.

You can look back in the archives for posts that cover this topic, though I should mention that the younger organizations mentioned as being involved in work on this are mostly defunct or going nowhere, it seems. Finding funding is an issue, though the Florida clinical trial partially funded by the Life Extension Foundation is apparently still ongoing. Good for them.

A reader pointed me to recently published research on the cancer-immune mice that reinforces the previous work by Zheng Cui and others, demonstrating once more a transfer of cancer immunity between mice, but the authors note that the approach isn't as general as hoped - meaning that there are other factors at work that will make it much more of a hard slog to either (a) find a donor with immune cells that will work on your cancer, or (b) figure out how what's going on under the hood here. Why does it work for some cancers and not for others? So it's the same old story: biology is always considerable more complicated than we'd like it to be. Granulocyte transplants are very effective when they do work, however, not just causing remission of cancer, but also granting immunity. This means that research will continue, though as usual never as rapidly nor with as much funding as we'd like.


When I discuss the corrosive effects of regulation on progress in medicine, such as the enormous and entirely unnecessary costs and barriers put in place by the US Food and Drug Administration (FDA), I usually focus on the research and development side of the coin: the process of creating new therapies. That is greatly impacted, not least because as the system presently stands it is actually impossible to gain approval for any treatment for degenerative aging - no medicine is permitted into the clinical trial system if its purpose is to treat old people to reverse some of their symptoms. The FDA doesn't recognize aging as a named medical condition that can be be treated, and there is no path short of complete revolution in the regulatory system in the US to make this any different.

The costs and prohibited actions due to the FDA propagate back down the fundraising chain. You can't raise venture capital if there's prospect for selling the resulting therapy. It's harder to raise funds for basic research when there's no connection to later commercial activity. There are thus far fewer research groups working on potentially important ways to address aging than there might be, and less press and public understand of what might happen if the FDA were not standing in the way, a hideous roadblock, a ball and chain that stops the research community from improving the human condition. The invisible costs, the therapies that might have existed but do not because of regulation, are always the hardest to make people understand.

But that's just one side of the coin. The other side is the provision of medical services: once therapies exist, how are they delivered, priced, and bought and sold? Here the institutions of regulation have just as horrific and corrosive an effect, raising costs and reducing availability to no good end - a system has come into being that benefits no-one, as every individual would be better off under a free market for medical services, and yet this system seems destined to become even worse in the future. Perverse short term incentives steer us all in the wrong direction. You might click through to this Fight Aging! post for pointers to an article giving a very clear example of all that's going wrong with medicine today.

If provision of medicine stultifies, then so does much of the impetus for research. In the field of aging and human longevity that matters greatly - we're on a timer, all aging to death one day at a time, and cannot afford to suffer through decades of collapse and slow progress in research, development, and provision of medical services. To my eyes the present system is doomed; the only way through is for it to fail utterly in one way or another. The most plausible collapse is the one the US regulatory monolith continues to exist, a drain on the declining US, but where near everyone travels to Asia-Pacific countries or other less regulated destinations for any meaningful medical services - in other words much like the UK, or other European countries. The only hope for the future is competition through medical tourism, which requires that other advanced regions of the world maintain far less onerous regulations for medicine.


Human calorie restriction studies continue onward at the normal sedate pace of all human research, as noted in a recent post on the CALERIE program. It remains the case that the vast majority of work on calorie restriction and its beneficial effects involves mice, flies, worms, and other laboratory animals. Most such species exhibit increased longevity and improved measures of long term health when on a calorie restricted diet, provided that they still receive suitable levels of nutrition. That this is so universal is one of the reasons to suggest calorie restriction with optimal nutrition as a lifestyle choice in humans.

Other reasons include the results from human studies to date; if there was a pill you could take that provided half the benefits that calorie restriction has been shown to produce in humans, then everyone would be falling over themselves to take it. It's somewhat harder to convince people to eat less in this day and age, however, no matter how beneficial the results might be. The paper quoted below is illustrative of results from human studies, in that the measures taken tend to line up with what is seen in short-lived animals like mice and rats:

"Here we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR-induced dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation."

The fact that more easily gathered measures of metabolism like those noted above are similar for rat and human calorie restriction makes CR look like a good option - where these measures match up, the hope is that the long term rewards do so as well. Studies in rats can achieve what studies in humans cannot, which is to follow large numbers of rats for their entire lives and catalog the impressive long term health benefits, as well as the characteristic increase in life expectancy, that accompanies CR in rodent species.


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!



Friday, April 26, 2013
Some people are more predisposed to suffer Parkinson's disease than others, a fraction of those due to mutations in genes involved in mitochondrial quality control. The state of mitochondrial function shows up as an important component of many different conditions and indeed in aging itself. In Parkinson's disease it is thought that mitochondrial dysfunction contributes to the conditions in which the population of dopamine-producing neurons in the brain die off, producing the characteristic symptoms of the disease. It may be that more of Parkinson's disease is genetic than was previously thought, and the odds of that being the case increase as the chain of molecular machinery involved in mitochondrial quality control is followed and new components identified. This sort of work also helps clarify the mechanisms associated with mitochondrial dysfunction in aging: "Mitofusin 2 (Mfn2) is known for its role in fusing mitochondria together, so they might exchange mitochondrial DNA in a primitive form of sexual reproduction. "Mitofusins look like little Velcro loops. They help fuse together the outer membranes of mitochondria. Mitofusins 1 and 2 do pretty much the same thing in terms of mitochondrial fusion. What we have done is describe an entirely new function for Mfn2." Mitochondria work to import a molecule called PINK. Then they work to destroy it. When mitochondria get sick, they can't destroy PINK and its levels begin to rise. Once PINK levels get high enough, they make a chemical change to Mfn2, which sits on the surface of mitochondria. This chemical change is called phosphorylation. Phosphorylated Mfn2 on the surface of the mitochondria can then bind with a molecule called Parkin that floats around in the surrounding cell. Once Parkin binds to Mfn2 on sick mitochondria, Parkin labels the mitochondria for destruction. The labels then attract special compartments in the cell that "eat" and destroy the sick mitochondria. As long as all links in the quality-control system work properly, the cells' damaged power plants are removed, clearing the way for healthy ones. "But if you have a mutation in PINK, you get Parkinson's disease. And if you have a mutation in Parkin, you get Parkinson's disease. About 10 percent of Parkinson's disease is attributed to these or other mutations that have been identified." The discovery of Mfn2's relationship to PINK and Parkin opens the doors to a new genetic form of Parkinson's disease."

Friday, April 26, 2013
The electron transport chain is the core piece of biological machinery inside mitochondria, the cell's power plants. It occupies a central place in the various free radical theories of aging as well. A good number of longevity-related mutations in laboratory animals appear to alter electron transport chain function as their primary mode of operation, and a good case is made for a large portion of degenerative aging to rest atop damage to the mitochondrial genes that encode proteins essential to proper electron transport chain function. "Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. [Although overexpression of CAT has been shown to extend life in mice by some groups]. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity." Personally I think the better approach to testing theory here is to implement mitochondrial repair or replacement, both of which are very feasible, and see what effect that has on older animals. It will both extend life and produce some degree of rejuvenation if the mitochondrial free radical theory of aging is correct.

Thursday, April 25, 2013
Damage to mitochondrial DNA accumulates as a side-effect of the operation of mitochondria in your cells, and per the mitochondrial free radical theory of aging proceeds to cause some fraction of degenerative aging though a long chain of ever worsening consequences. Below you'll find recently published research that shows long-lived mice to have less mitochondrial DNA damage, which is what you'd expect to see under this model. This reinforces the need for ways to repair or replace mitochondrial DNA throughout the body in order to remove this contribution to degenerative aging. A wide range of possible approaches exist, but currently little funding is devoted towards realizing them and there is no path to getting treatments to reverse aging through the regulatory process - the standard lament when it comes to rejuvenation biotechnology. "The single gene mutation of Ames dwarf mice increases their maximum longevity by around 40% but the mechanism(s) responsible for this effect remain to be identified. This animal model thus offers a unique possibility of testing the mitochondrial theory of aging. In this investigation, oxidative damage to mitochondrial DNA (mtDNA) was measured for the first time in dwarf and wild type mice of both sexes. In the brain, 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) in mtDNA [a measure of oxidative stress] was significantly lower in dwarfs than in their controls both in males (by 32%) and in females (by 36%). The heart of male dwarfs also showed significantly lower mtDNA 8-oxodG levels (30% decrease) than the heart of male wild type mice, whereas no differences were found in the heart of females. The results, taken together, indicate that the single gene mutation of Ames dwarfs lowers oxidative damage to mtDNA especially in the brain, an organ of utmost relevance for aging. Together with the previous evidence for relatively lower level of oxidative damage to mtDNA in both long-lived and caloric restricted animals, these findings suggest that lowering of oxidative damage to mtDNA is a common mechanism of life extension in these three different mammalian models."

Thursday, April 25, 2013
Organovo has demonstrated the 3-D printing of small amounts of functional liver tissue, suitable for use in research. The limiting factor for printing larger masses is at this time largely the challenge of creating a suitable blood vessel network - something that researchers are still working on. "For the first time, human liver tissues have been generated that are truly three-dimensional, being up to 500 microns in thickness in the smallest dimension, and consisting of multiple cell types arranged in defined spatial patterns that reproduce key elements of native tissue architecture. The tissues, fabricated using Organovo's [bioprinting] platform, are highly reproducible and exhibit superior performance compared to standard 2D controls. "We have achieved excellent function in a fully cellular 3D human liver tissue. We've combined three key features that set our 3D tissues apart from 2D cell-culture models. First, the tissues are not a monolayer of cells; our tissues are approximately 20 cell layers thick. Second, the multi-cellular tissues closely reproduce the distinct cellular patterns found in native tissue. Finally, our tissues are highly cellular, comprised of cells and the proteins those cells produce, without dependence on biomaterials or scaffold for three-dimensionality. They actually look and feel like living tissues. Not only can these tissues be a first step towards larger 3D liver, laboratory tests with these samples have the potential to be game changing for medical research. We believe these models will prove superior in their ability to provide predictive data for drug discovery and development, better than animal models or current cell models.""

Wednesday, April 24, 2013
Cartilage is one of the more challenging tissues to regenerate - it's comparatively easy to grow something that's more or less like cartilage, but it's proven hard to reproduce the necessary small-scale structure and mechanical properties of the real thing. So work continues in laboratory animals: "[Researchers] have suggested that articular cartilage defects can be repaired by a novel thermo-sensitive injectable hydrogel engineered with gene modified bone marrow mesenchymal stromal cells (BMSCs). The chitosan and polyvinyl alcohol composite hydrogel containing hTGFβ-1 gene modified BMSCs was injected into rabbits with defective articular cartilage. Sixteen weeks later the defected cartilage regenerated. No reliable approach is currently available for complete restoration of damaged articular cartilage. Tissue engineering combined with gene therapy technology has the potential to manage the repair of defective articular cartilage. CS/PVA gel can be applied to the repair of articular cartilage defects as an injectable material in tissue engineering, and the regenerated cartilage can secrete cartilage matrix and perform the functions of hyaline cartilage. Use of this gel for cartilage repair has advantages such as the minor surgical procedure required, tight bonding with the damaged tissue and lack of rejection."

Wednesday, April 24, 2013
Here is one of many examples of different forms of targeted cancer therapies under development. Most use nanoparticles, immune cells, or viruses as the agent that selectively transports a cell-killing mechanism to the cancer cells, but bacteria are also a viable possibility: "[Researchers] have developed a therapy for pancreatic cancer that uses Listeria bacteria to selectively infect tumor cells and deliver radioisotopes into them. The experimental treatment dramatically decreased the number of metastases (cancers that have spread to other parts of the body) in a mouse model of highly aggressive pancreatic cancer without harming healthy tissue. Several years ago, scientists observed that an attenuated (weakened) form of Listeria monocytogenes can infect cancer cells, but not normal cells. [The] tumor microenvironment suppresses the body's immune response, allowing Listeria to survive inside the tumors. By contrast, the weakened bacteria are rapidly eliminated in normal tissues. Scientists later showed that Listeria could be harnessed to carry an anti-cancer drug to tumor cells in laboratory cultures, but this concept was never tested in an animal model. These findings prompted [researchers to couple] a radioactive isotope called rhenium to the weakened Listeria bacteria. "We chose rhenium because it emits beta particles, which are very effective in treating cancer. Also, rhenium has a half-life of 17 hours, so it is cleared from the body relatively quickly, minimizing damage to healthy tissue." Mice with metastatic pancreatic cancer were given intra-abdominal injections of the radioactive Listeria once a day for seven days, followed by a seven-day "rest" period and four additional daily injections of the radioactive bacteria. After 21 days, the scientists counted the number of metastases in the mice. The treatment had reduced the metastases by 90 percent compared with untreated controls. In addition, the radioactive Listeria had concentrated in metastases and to a lesser extent in primary tumors but not in healthy tissues, and the treated mice did not appear to suffer any ill effects."

Tuesday, April 23, 2013
CALERIE is an ongoing series of studies on calorie restriction in humans and its effects on measures of health and metabolism. In this blog post you'll find some notes on results from the latest phase, yet to be published formally, but presented at conferences: "Three speakers described how a select group of 220 healthy volunteers [chose] to shun a quarter of their dietary calories in the hope of improving their long-term health and, potentially, extending lifespan. These participants of the CALERIE phase 2 trial were randomized to 25 percent CR or ad libitum eating. The large NIH-funded, mulitcenter, parallel group, randomized controlled trial was designed to evaluate how a calorie restricted diet affected biomarkers of aging and age-related disease over the long-term. The primary aim of the trial [was] to evaluate whether 25 percent CR resulted in a sustained metabolic adaptation. One of the underlying theories of how CR worked is that attenuates the biological aging process by reducing resting metabolic rate (RMR) leading to reduced cumulative oxidative damage from aerobic respiration. [However] the calorie restriction did not cause a change in body temperature that would be indicative of reduced resting metabolic rate that would show adaptation. These data (which are not published yet) are currently being evaluated for proper interpretation. [The] findings are interesting because they are inconsistent with previous studies in animals and a recently in humans showing a metabolic adaptation through RMR and core body temperature in response to CR. "Basically, these are the primary mechanisms in humans - reduction of metabolic rate and core body temperature - we did not find an adaptation in the resting component, but we did find an adaptation in the non-resting component. If there was a reduction, that is supposed to lend support to the oxidative theory. What exactly this means is still being worked out." The long-term CR had a significant effect on a variety of [cardiovascular disease risk factor] measurements including a reduced metabolic syndrome score, reduced systolic blood pressure, reduced LDL, reduced triglycerides, and increased HDL that were maintained over the study. There were no significant differences on glucose measures or inflammatory markers IL-6 and TNF-a. These results are consistent with previous studies related to reductions in body weight."

Tuesday, April 23, 2013
The CR Society is a long-standing organization that promotes and provides information about the practice of calorie restriction with optimal nutrition, something shown to extend life and greatly improve measures of health in many species. There are some thousands of members, and the Society mailing lists are quite busy. The Society has done well over the years in encouraging research into the long-term health and potential longevity benefits of calorie restriction in humans, and is an excellent example of what can be achieved by building strong ties between health advocates and the scientific community. The next CR Society conference is coming up in June, so there's still time to register: "The next CR Society conference will be held at the Buck Institute for Research on Aging in Novato California June 5 - 8, 2013. This conference will mark the 10-year anniversary of the founding of the CR Society as a non profit organization. The topics will include CR and Cancer, CR Primate Studies, Biological Clocks and Physical Activity, Stem cell/senescence/rejuvenation. This will be a very special opportunity to interact with CR comrades, and researchers at the Buck Institute, see and tour the Buck Institute - not to be missed!"

Monday, April 22, 2013
Within a given species, larger individuals tend to age faster and die younger. Between species, larger species tend to live longer - though there are many exceptions to this rule. Here is an open access article on this phenomenon from a programmed aging perspective, i.e. the author is building on his hyperfunction theory to say that aging is a genetic program of growth that runs awry to cause damage in old age, past the point at which evolutionary selection guides its operation. This is as opposed to aging as straightforward "wear and tear" type damage that accumulates as a result of the normal operation of metabolism over time, becoming meaningfully harmful only past the age at which evolutionary selection favors further adaptations to reduce, avoid, or repair this damage. "It has been known for millennia that large animals live longer, inspiring numerous theories of aging. For example, elephants and humans live longer than mice, which in turn live longer than worms and flies. The correlation is not perfect, with many explainable exceptions, but it is still obvious. In contrast, within each species (e.g., mice and some other mammals) small body size is associated with longevity and slow aging. The concept that aging (and age-related diseases) is an aimless continuation of developmental growth, a hyperfunction driven by the same nutrient-sensing and growth-promoting pathways such as MTOR, may explain this longstanding paradox. Fast versus slow aging may depend on whether the organism "grows fast" or "develops longer": first case should be associated with high MTOR. Exceptions may be numerous. Small size is not always related to the GH/IGF/MTOR pathway but instead may be caused by defects that shorten life span. But understanding of each exception will further illuminate the rules. On a wider scale (from worm to whale), large animals live longer because aging is quasi-programmed. In contrast, "big" mice live shorter because they grow faster than dwarf mice and growth is driven by the same pathways that drive aging. Fast-growing mice are expected to have over-activation of growth-promoting pathways (either by excessive calorie consumption or due to genetic mutations), which drive aging and age-related diseases later. Cellular hyperfunction is the key feature of aging cell, leading to organismal death. Yet, there are also two other crucial aspects of hyperfunction theory: (a) aging as a quasi-program of developmental growth and (b) both processes are driven by the same growth-promoting-signaling pathways including MTOR."

Monday, April 22, 2013
This study result is contrary to the mainstream view, which is that absent advances in medicine the risk of suffering dementia will continue to rise along with life span. However, it makes sense from a reliability theory point of view; if aging and dysfunction and life span are all consequences of the level of damage suffered in cells and molecular machinery, then reducing that damage should extend life by slowing aging and also reducing dysfunction. "The risk of developing dementia may have declined over the past 20 years, in direct contrast to what many previously assumed. The result is based on data from SNAC-K, an ongoing study on aging and health that started in 1987. "We know that cardiovascular disease is an important risk factor for dementia. The suggested decrease in dementia risk coincides with the general reduction in cardiovascular disease over recent decades. Health check-ups and cardiovascular disease prevention have improved significantly in Sweden, and we now see results of this improvement reflected in the risk of developing dementia." The result shows the prevalence of dementia was stable in both men and women across all age groups after age 75 during the entire study period (1987-1989 and 2001-2004), despite the fact that the survival of persons with dementia increased since the end of the 1980s. This means that the overall risk of developing dementia must have declined during the period, possibly thanks to prevention and better treatment of cardiovascular disease. "The reduction of dementia risk is a positive phenomenon, but it is important to remember that the number of people with dementia will continue to rise along with the increase in life expectancy and absolute numbers of people over age 75.""



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