Longevity Meme Newsletter, December 6th 2010

December 6th 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.



- Sight to the Blind, Muscles to the Weak
- Destroy the Bad Components or Age More Rapidly
- Telomerase and Aging in the News Again
- Mitochondrial Rejuvenation Demonstrated
- Latest Headlines from Fight Aging!


You'll find examples of present day regenerative medicine research in this Fight Aging! post:


"Using stem cells salvaged from the retinas of human cadavers, researchers with the University of Toronto have restored sight to the eyes of, well, three blind mice. The feat, aside from indicating a quirky sense of humour, has been repeated several times over the last year and marks an important step toward the goal of restoring sight in people. ... All the basic biology of the human eye and retina is the same as it is in the mouse. If we can get enough of the cells to grow and integrate, I think we'd go right into [trials with] humans.

"Researchers at the University of Colorado at Boulder and the University of Washington discovered that stem cells injected into mouse muscles led to increased growth for the rest of the mouse's life. Young mice with injured legs were given donor muscle stem cells from other young mice. Those injuries not only healed, but muscle mass increased 50% and muscle volume increased by an incredible 170%! Performance tests show the muscles were twice as strong as normal, and still above average when you control for size. Two years later, about the lifetime of a mouse, the legs were still bigger and stronger than normal, much to the scientists surprise."


What does reliability theory tell us about the mechanisms of aging? Some thoughts follow:


"An appreciation of reliability theory is a good way to better put into context ongoing research into the cellular and molecular mechanics of aging. Reliability theory was developed to better predict the failure rates and times to failure of complex systems consisting of many redundant components - such as ships, electronic circuitry, or even we humans ... Modeling a human being as a collection of many, many redundant parts (representing cells, or clusters of cells) produces results that match the observed demographics of aging and life expectancy very well. This approach is further supported by the observed benefits of increased autophagy and apoptosis on health and longevity. ... Both autophagy and apoptosis act to remove broken components of the body before they can cause harm. If either process is globally impaired, then the result is what amounts to faster aging: a more rapid accumulation of cellular damage that then itself causes further damage.

"Can autophagy and apoptosis be enhanced in the near future to bring general benefits to health and longevity? Quite possibly: calorie restriction mimetic research may eventually result in designer drugs intended to enhance autophagy, given the importance of autophagy to the benefits produced by calorie restriction. You might look at the work on spermadine as an example of a first step along this path. Conceptually similar work on apoptosis takes place in the cancer research community, where apoptosis is viewed as a dominant mechanism of cancer suppression. The bottom line is that these are signaling challenges: the body is capable of boosted autophagy and apoptosis in response to certain environment conditions, and researchers can in principle learn how to issue the signals to trigger that same boost without unwanted side-effects."


The mass media has paid considerable attention to recent research on removing and then restoring the enzyme telomerase in mice. I think this is unhelpful, as the work has no application towards longevity science:


"It's interesting stuff, but unfortunately this present research is being headlined as 'scientists reverse aging in mice' - which is absolutely not what was accomplished. Reversing an artificially created accelerating aging condition by removing its cause is not the same thing as intervening in normal aging, and it will rarely have any relevance to normal aging. ... The bottom line is that it is really only worth getting excited over a study that shows extension of life rather than an un-shortening of life. It's all too easy to create short-lived mice and then make them less short-lived - hundreds of studies have achieved this result in one way or another. Also bear in mind that the media and public at large don't tend to seize upon one specific research result above another for any rational reasons. When it comes to what is shouted from the loudspeakers on a given day, it's all a matter of accident and marketing rather than facts and understanding. For example, you might recall that telomerase and p53 were used to extend normal mouse life span by 50% a few years ago - far more important and interesting than this present study, yet it received next to no attention."

If excitement over items that don't advance longevity science did in fact generate more funding and progress for the research that does matter, then the "anti-aging" marketplace of frauds and potions would be a net plus for the future of health and longevity. But it isn't, and neither is this work on telomerase.


Researchers have uncovered an unexpected side-effect of the methods used to convert normal cells into the induced pluripotent stem cells that may ultimately replace embryonic stem cells in regenerative medicine research:


"In essence the researchers did the following: (a) Start with fibroblast cells that have bad, damaged mitochondria, (b) Produce induced pluripotent stem cells (IPSCs) from the fibroblasts, (c) Then direct the IPSCs to differentiate into more fibroblasts, (d) Lo and behold, the new fibroblasts have good, functional mitochondria.

"If there is a mechanism there to be exploited, perhaps it may be usefully applied to the development of stem cell therapies for the aged. One of the big potential issues with the whole field of tissue engineering and stem cell medicine is that old people have old stem cells and old biochemistries: damaged, dysfunctional, and problematic. But at the same time, old people are those who need these therapies the most. Therefore we want to know that there are ways to include the repair of cellular damage in any potential stem cell therapy or tissue engineering project - an extra step in between taking the source cells from the patient and then returning the modified therapeutic cells."

Damaged and dysfunction mitochondria are, you might recall, one of the contributions to aging:


This discovery cannot be used to reverse the mitochondrial decline within your body, but it may demonstrate that the age of the patient is not as great an obstacle to effective regenerative medicine as feared.


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, December 3, 2010
The mainstream of longevity research is the domain of metabolic exploration and manipulation: scientists in search of a better human metabolism that will age at a somewhat slower rate. This is a realm apart from the minority efforts to repair biological damage and thereby reverse aging. Here is an example of the sort of metabolic research presently taking place: "scientists report finding a molecular 'switch' that can 'turn off' some cellular processes that are protective against aging and metabolic diseases. While more research is needed, the findings may open doors for new drug treatments to halt or slow development of metabolic diseases like type 2 diabetes or heart disease. ... [Researchers] focused on the role of the protein SMRT (silencing mediator of retinoid and thyroid hormone receptors) in the aging process. They found aged cells accumulate more SMRT and wanted to see if SMRT increases the damaging effects of oxidative stress on mitochondria, the cell component that converts food and oxygen into energy and powers metabolic activities. Oxidative stress is a cellular process that damages DNA, protein, and other cell functions and can lead to age-related diseases such as type 2 diabetes, Alzheimer's, Parkinson's, and atherosclerosis. ... in older animals SMRT acts like a 'switch,' turning off the protective cellular activities of proteins known as peroxisome proliferator-activated receptors (PPARs). PPARs help regulate genes that promote fat burning to maintain lipid (blood fat) balance and reduce oxidative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on."

Friday, December 3, 2010
Egalitarianism is a dangerous philosophy - as practiced throughout history it seems to involve a lot more tearing down and destruction than building up and progress. We are hardwired to manage equality in small hunter-gather groups, but these same impulses in a large society lead to hideous end states like the old Soviet Union. Despite this history, egalitarianism remains very popular, and here is an egalitarian view of the imperative to develop technologies of engineered longevity: "Most egalitarians will not have the intuition that tackling aging is a requirement of equality. Why not? For starters, most egalitarians will assume that, because aging is universal, there is no inequality that warrants mitigating... end of story. But this assumption is false. While it is true that everyone chronologically ages at the same rate (i.e. we each age 1 year every 12 months), there is a significant variation in the rate of biological aging. That is, the rate at which we experience the molecular and cellular decline that gives rise to morbidity and, ultimately, death. So there is an inequality at stake here. But, our egalitarian might retort, this inequality is trivial. Again, this assumption is false. The stakes are very significant indeed. We are talking about an extra 20-30 years of health for some (rare) fortunate individuals. And what explains their exceptional health and longevity is not their exceptional lifestyles, but rather the fact that they have inherited longevity genes. ... I think that is the basis of a pretty solid case for supporting the aspiration to retard human aging. Getting to that conclusion requires a lot more work than simply appealing to some basic egalitarian intuitions. But that simply illustrates another important point - egalitarians ought to invest less of their energies fine tuning their egalitarian intuitions and more time and energy in understanding the empirical realities of the world (especially the human species)."

Thursday, December 2, 2010
Another benefit of exercise: "exercise increased the number of satellite cells (muscle stem cells) - a number which normally declines with aging. The researchers believe that a decline in the number of these cells and their functionality may prevent proper maintenance of muscle mass and its ability to repair itself, leading to muscle deterioration. Comparing the performance of rats of different ages and sexes, they found that the number of satellite cells increased after rats ran on a treadmill for 20 minutes a day for a 13-week period. The younger rats showed a 20% to 35% increase in the average number of stem cells per muscle fiber retained - and older rats benefited even more significantly, exhibiting a 33% to 47% increase in stem cells. ... Endurance exercise also improved the levels of 'spontaneous locomotion' - the feeling that tells our bodies to just get up and dance - of old rats. Aging is typically associated with a reduced level of spontaneous locomotion. The combination of aging and a sedentary lifestyle significantly contributes to the development of diseases such as osteoporosis, obesity, diabetes and cardiovascular diseases, as well as a decline in cognitive abilities. If researchers can discover a method to 'boost' satellite cells in our muscles, that could simulate the performance of young and healthy muscles - and hold our aging bones in place."

Thursday, December 2, 2010
From Singularity Hub: "the US FDA has granted approval for clinical trials for a therapy derived from human embryonic stem cells. Advanced Cell Technology (ACT), a Massachusetts based bio-firm, recently announced that they had secured approval for human trials of their retinal pigment epithelial cells to treat Stargardt's Macular Dystrophy. SMD causes blindness, generally among youths 10 to 20 years in age, and affects less than 200,000 people in the US. The recently approved trials will only involve 12 patients, and are looking primarily to establish that using the ACT cells is safe. There is hope, however, that the vision of those treated could be improved or restored. In the longer term a success for embryonic stem cells here could lead to treatments for other forms of blindness. Yet as exciting as this study may be it's also a sad reminder of how long it has taken to get embryonic stem cells approved for human trials. ... I'm also frustrated, as I know many of you are as well, that promising stem cell technologies are taking so long to get to patients. Both Geron and ACT had remarkable success in their animal models. Geron got mice walking again after spinal injury and ACT had 100% success with getting rodents to grow new retinal cells after treatments (100 percent!). It's disappointing to think that either a) the FDA doesn't recognize the overwhelming potential of these treatments and isn't willing to help them move along as fast as possible OR b) has been helping them, and this is as fast as it possibly can get."

Wednesday, December 1, 2010
Type 2 diabetes is a lifestyle disease for nearly all people - for them, it is a choice to be fat, sedentary, and overfed, and thereby risk damaging consequences to long-term health. The costs are becoming well enumerated: "Despite medical advances enabling those with diabetes to live longer today than in the past, a 50-year-old with the disease still can expect to live 8.5 years fewer years, on average, than a 50-year-old without the disease. ... The analysis - based on data from the Health and Retirement Study (HRS) - found that older adults with diabetes have a lower life expectancy at every age than those without the disease. At age 60, for example, the difference in life expectancy is 5.4 years. By age 90, the difference is one year. ... the figures show a marked increase in the percentage of adults over age 50 with diabetes during the past decade: from 11 percent of non-Hispanic whites in 1998 to 18 percent in 2008, and from 22 percent of non-Hispanic blacks in 1998 to 32 percent in 2008. The report [also] found that, compared to older adults without diabetes, those with the disease are less likely to be employed and more likely to have other health problems, such as heart disease, depression, and disabilities that interfere with normal life activities. ... Diabetes currently afflicts 7.8 percent of the total U.S. population - 23.6 million people, including 5.7 million undiagnosed - but almost a quarter (23.1 percent) of individuals age 60 or older (12.2 million people)."

Wednesday, December 1, 2010
A good article on cancer stem cells : "The stem cell theory of cancer proposes that a relatively small number of rare stem cells drive tumor formation and progression. The majority of cancer cells, cancer stem cell (CSC) theory advocates say, can't sustain the tumor nor establish it elsewhere in the body; only CSCs are tumorigenic and have a metastatic phenotype. The CSC theory has significant implications for cancer research and therapy and may explain why treatments focused on reducing tumor mass by removing proliferating cells fail to eliminate tumors. Or maybe not. Despite a large number of publications supporting the existence of stem cells in tumors including human blood-cell derived cancers and solid tumors of the brain, breast, colon, pancreas, prostate, and skin, the issue of CSCs remains in serious contention. ... I think that there are some cancers that do clearly follow a cancer stem cell model, but it will be more complicated than what's been presented so far ... The existence of stem cells in tumors has been invoked to explain why some cancers keep going, no matter what chemotherapies or immunotherapies are used. Stem cells usually cycle slowly and thus are relatively insensitive to treatments aimed at stopping cell replication. CSCs are more resistant to conventional cancer drugs not only due to quiescence relative to cancer cells but also because they are characterized by increased expression of antiapoptotic proteins and drug efflux transports. Additionally, according to recent findings, they rapidly change antigen expression, making them unlikely targets for immunotherapies that target cell surface proteins."

Tuesday, November 30, 2010
A promising study in mice: researchers "have discovered a new strategy to prevent memory deficits in a mouse model of Alzheimer's disease (AD). Humans with AD and mice genetically engineered to simulate the disease have abnormally low levels of an enzyme called EphB2 in memory centers of the brain. Improving EphB2 levels in such mice by gene therapy completely fixed their memory problems. ... EphB2 [acts] as both a receptor and an enzyme. We thought it might be involved in memory problems of AD because it is a master regulator of neurotransmission and its brain levels are decreased in the disease. ... To determine if low EphB2 levels actually contribute to the development of memory problems, the investigators used gene therapy to experimentally alter EphB2 levels in memory centers of mice. Reducing EphB2 levels in normal healthy mice disrupted neurotransmission and gave them memory problems similar to those seen in AD. ... Increasing EphB2 levels in neurons of mice engineered to produce high levels of human amyloid proteins in the brain prevented their neurotransmission deficits, memory problems and behavioral abnormalities. The scientists also discovered that amyloid proteins directly bind to EphB2 and cause its degradation, which helps explain why EphB2 levels are reduced in AD and related mouse models. ... Based on our results, we think that blocking amyloid proteins from binding to EphB2 and enhancing EphB2 levels or functions with drugs might be of benefit in AD."

Tuesday, November 30, 2010
From Maria Konovalenko: "I'd like to draw your attention to Jan Vijg's words: 'People are a little afraid to confess that they want to cure aging. I think it would be a good thing to make it very clear that that is exactly what we want to do, we want to try to get rid of aging.' Dr. Vijg discerned one of the major problems in biogerontology - the fear and pretence of the scientists, who want the grant money, but don't want to sound 'inappropriate.' I have to say this approach of not saying what you have in mind is lethal. For everybody. Why is so much money being spent on cancer research? Because cancer researchers cry out loud that cancer is a very dangerous disease that needs to be cured. They clearly state their goal. Biogerontologists, on the other hand, would never say their goal is to cure aging. This is why they don't get the money. This is why the whole field rather survives, not lives. I believe this attitude has to change. Researchers have to state their noble goal - to defeat aging. They should be neither afraid, nor embarrased to say this explicitly. This is the only right way to get public attention and needed grant money for studying the fundamental mechnisms of our worst disease - aging."

Monday, November 29, 2010
Another demonstration of the potential utility of autologous stem cell therapies: "A spray solution of a patient's own stem cells is healing their severe burns. So far, early experiments under a University of Utah pilot project are showing some remarkable results. What was once a serious burn on Kaye Adkins foot is healing nicely now because of a topical spray. With diabetes as a complication, the small but open wound had not healed after weeks of failed treatments. ... With a wound that is open for several months, as this patient suffered prior to seeing us in our burn clinic, we worry about a pretty heavy bacterial load there. ... But enter the evolutionary world of regenerative medicine, using almost a bedside stem cell technique that takes only about 15 minutes. With red cells removed, a concentrate of platelets and progenitor cells is combined with calcium and thrombin. The final mixture looks almost like Jello. Though her own skin graft had failed before, the topical spray was used during a second graft. It 'took' and healed. ... Adkins burn is healing and so is her heart. Coincidentally, stem cells were used during her bypass surgery five weeks ago to hasten healing for that procedure as well. While hundreds of heart patients have had stem cell treatments, burn patients are still few in numbers. Cardiothoracic surgeon Amit Patel and burn care surgeon Amalia Cochran are experimenting on small burns for now. But down the road, both are hoping for large scale clinical trials on patients with much larger burns."

Monday, November 29, 2010
This interview with Aubrey de Grey and David Brin encapsulates the divide in longevity science. On the one side, people who see repair-based methodologies like SENS and the reversal of aging as the best way forward, and who foresee great progress within a few decades after major funding is achieved. On the other, people who look towards changing metabolism to slow aging, and who foresee little progress over the next few decades because the challenge of building a new, viable human metabolism is very, very hard. From de Grey's side of the article: "I think we have a 50% chance of achieving medicine capable of getting people to 200 in the decade 2030-2040. Presuming we do indeed do that, the actual achievement of 200 will probably be in the decade 2140-2150 - it will be someone who was about 85-90 at the time that the relevant therapies were developed. There will be no one technological breakthrough that achieves this. It will be achieved by a combination of regenerative therapies that repair all the different molecular and cellular degenerative components of aging." As a counterpoint, from Brin's side of the article: "I do not expect this any time soon. There are way too many obstacles. First, there is no low-hanging fruit. Simple switches, like the ones that are flipped in many animals, by caloric restriction or celibacy, are there to give creatures a delayed chance at reproduction, if it cannot happen earlier. These switches have already been thrown in humans. All of them! Because we had genuine darwinistic reasons to evolve longest possible lifespans. When the lore held by grandparents helped grandchildren to survive, we evolved a pattern where the tribe would always have a few grandparents around, who remembered stuff."



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