Fight Aging! Newsletter, May 30th 2011
FIGHT AGING! NEWSLETTER
May 30th 2011
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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CONTENT
- Countries, Medical Tourism, Law: Research Volunteers Wanted
- Senescent Cells Make Lungs More Vulnerable
- Three Parallel Tracks
- The Most Important Debate in Longevity Science
- Discussion
- Latest Headlines from Fight Aging!
COUNTRIES, MEDICAL TOURISM, LAW: RESEARCH VOLUNTEERS WANTED
I am looking for volunteers to help assemble some foundational information for the Open Cures initiative:
"[Later phases of the Open Cures initiative involve] building relationships with the medical tourism industry and developers outside the US. At present I have just as little an idea of the fine details of that process as you do - but discovery is half the challenge in building any initiative. This is where research and volunteers come into the picture. There is a great deal of very useful information out there in various websites and publications that I would like to see assembled into one place - or at least the references to it all assembled in one place. This is light research work that any smart person with an internet connection can undertake, and it can take place in parallel to other foundational work for Open Cures - and be accomplished piecemeal by many different people. Many hands make light work."
So I am looking for volunteers to help assemble basic information on the state of medical tourism on a country by country basis, listing out the major players in the industry, and itemizing data on medical investment and development. Take a look at the link above for an initial list of line items. This may be a case of cleverly finding out that someone in the medical tourism industry has done much of this work already, but I think there's a little more to it than that. To my mind the eligible countries include much of the Asia-Pacific region, India, and a few others - but validating that list with real numbers is one of the tasks on the table.
SENESCENT CELLS MAKE LUNGS MORE VULNERABLE
Senescent cells accumulate in our tissues with age: these are cells that become damaged or worn, fall out of the normal cell cycle, but fail to self-destruct as they are programmed to do. The immune system should hunt down and destroy these errant cells, but it too becomes worn with age. Growth in the senescent cell population has direct, material effects on health - such as this:
"The researchers found that when it comes to aging and pneumonia, one bad apple can ruin the barrel. Lung cells that were supposed to die due to DNA damage - but didn't - were 5 to 15 times more susceptible to invasion by pneumonia-causing bacteria. These bad apples also increased the susceptibility of normal cells around them. Both age and [pneumonia] are associated with senescent cells, which are unable to die due to dysregulated function. These cells have increased levels of proteins that disease-causing bacteria stick to and co-opt to invade the bloodstream. The cells also spew out molecules that increase inflammation, and make normal cells nearby do the same.
"How will we deal with senescent cells with near future biotechnology? The likely answer is through the use of technologies pioneered in cancer research: precision cell-killing strategies that can locate and destroy very specific types of cell without harming any other cell types. These may use nanoparticles or they may involve training the immune system to attack senescent cells with vigor, but both paths have been demonstrated effective in the laboratory."
THREE PARALLEL TRACKS
There are three parallel tracks along which the future development of longevity science must progress, and we'll reach the end goal only as rapidly as the slowest of the three tracks moves.
https://www.fightaging.org/archives/2011/05/three-parallel-tracks.php
"1) Science: The most obvious of the tracks is that the technologies of rejuvenation must be developed. We can see what the form that these technologies must take: damage repaired, waning cell populations renewed, waste byproducts broken down and removed, cancer thwarted. Initiatives like SENS can describe the needed procedures in great detail, at the level of cells and molecular machinery, as we truly are within a tantalizingly close reach of their creation.
"2) Clinical Development: Taking the output of the scientific method and turning it into reliable, affordable, widely available technology is no less a challenge than scientific progress. It is fraught with risk, and the stakes are much higher: the cost of developing new science is small in comparison to the costs of building an industry. Moving from one technology demonstration and a few patients to a technology used by hundreds of thousands of patients around the world is a massive undertaken in risk, development, innovation, and cutthroat competition.
"3) Persuasion: You can change the world with ten thousand people who think the same way as you do, that much is true, but it will be hard and it will take a long, long time. In the end, you'll only succeed by convincing hundreds of thousands more to contribute their support. It does't require all the world to agree with you. Half a percentage point of the world's population is hundreds of millions of people. Markets with hundreds of millions of customers are worth billions of dollars, even though they gain only a tiny, tiny fraction of the attention and expenditure of those people - and billions of dollars would be more than enough to fund the first emergence of true rejuvenation biotechnology."
THE MOST IMPORTANT DEBATE IN LONGEVITY SCIENCE
Will the research community focus on slowing aging through metabolic manipulation or reversing aging through repair of damaged biological machinery? This is what will determine whether we in fact live far longer healthy lives:
https://www.fightaging.org/archives/2011/05/the-latest-rejuvenation-research-and-the-most-important-debate.php
"It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.
"Whatever the course of research, the first resulting widespread therapies to significantly extend healthy human life are two or more decades away. Most of us will be old before the second generation of better and more reliable therapies emerges thereafter. Thus repair strategies for ongoing research must come to dominate the funding landscape over the next decade if we are to see meaningful progress in engineered human longevity within our lifetimes. Slowing aging will be of little use to us by the time it becomes available.
"All of this means that this scientific debate is far too important for all of us to refrain from participation. We should all absolutely dive in and loudly offer our own opinions on the topic, and help the researchers and fundraisers focused on repair biotechnologies succeed in their aims: it is, after all, the future of all our lives on the line."
DISCUSSION
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!
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LATEST HEADLINES FROM FIGHT AGING!
CONSCIENTIOUSNESS AND LONGEVITY
Friday, May 27, 2011
https://www.fightaging.org/archives/2011/05/conscientiousness-and-longevity.php
The conclusion of the researchers in this study is interesting, leaning as it does towards cognitive function rather than better implementation of health practices - though both general health and cognitive function are linked via mechanisms such as blood vessel health in the brain. Untangling the knots of many interrelated correlations in such complex things as human beings isn't easy: "Conscientious individuals tend to experience a number of health benefits, not the least of which being greater longevity. However, it remains an open question as to why this link with longevity occurs. The current study tested two possible mediators (physical health and cognitive functioning) of the link between conscientiousness and longevity. ... We tested these mediators using a 10-year longitudinal sample [of 512 people], a subset of the long-running Health and Retirement Study of aging adults. Measures included an adjective-rating measure of conscientiousness, self-reported health conditions, and three measures of cognitive functioning (word recall, delayed recall, and vocabulary) included in the 1996 wave of the HRS study. ... Our results found that conscientiousness significantly predicted greater longevity, even in a model including the two proposed mediator variables, gender, age, and years of education. Moreover, cognitive functioning appears to partially mediate this relationship. ... This study replicates previous research showing that conscientious individuals tend to lead longer lives, and provides further insight into why this effect occurs."
MORE TRANSDIFFERENTIATION, SKIN CELLS TO NEURONS
Friday, May 27, 2011
https://www.fightaging.org/archives/2011/05/more-transdifferentiation-skin-cells-to-neurons.php
Transdifferentiation is the act of changing a cell directly from one type to another, without having to first go through the process of producing induced pluripotent stem cells and then differentiating them into the desired final product. This shows some promise as a yet more effective way of producing cells to order for research and therapies: "Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins ... The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish. It may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells - seemingly on the basis of the proteins used to render them pluripotent. The new research parallels that of the same Stanford group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly. ... We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies. ... The direct conversion of skin cells to neurons contrasts with similar research that first transforms skin cells to a pluripotent, or developmentally flexible, state and then coaxes them to become neurons or other specialized cells. ... The iPS cell approach is doable and has been shown to work. We need to keep working on both strategies. It's possible that the best approach may vary depending on the disease or the type of research being done."
DAMAGE, LIFESPAN, AND ITS MEASUREMENT IN NEMATODE WORMS
Thursday, May 26, 2011
https://www.fightaging.org/archives/2011/05/damage-lifespan-and-its-measurement-in-nematode-worms.php
This open access work looks like a solid way to measure accumulated biochemical damage in nematode worms, and link it to both its causes and its resulting effects on life span: "A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers of remaining lifespan for Caenorhabditis elegans. In transgenic lines, we expressed fluorescent reporter constructs from promoters of C. elegans genes whose expression change with age. The expression levels of aging markers in individual worms from a young synchronous population correlated with their remaining lifespan. We identified eight aging markers, with the superoxide dismutase gene sod-3 expression being the best single predictor of remaining lifespan. Correlation with remaining lifespan became stronger if expression from two aging markers was monitored simultaneously, accounting for up to 49% of the variation in individual lifespan. ... Our results indicate that pathogenicity from Escherichia coli used as food is a major source of lifespan variability due to variable activation of the insulin-signaling pathway. ... E. coli, the common diet for worms, is mildly pathogenic whereas Bacillus subtilis is not pathogenic. Accordingly, worms fed B. subtilis live longer than worms grown on E. coli. ... The finding that the amount of sod-3 expression present in a middle-aged worm is correlated with its remaining lifespan indicates that events have occurred that affect its future aging trajectory. If so, feeding a worm either E. coli or B. subtilis should have greatest effect when it is young rather than when it is old. To test this, we fed worms one type of bacteria (E. coli or B. subtilis) when they were young and then shifted them to the other type of bacteria at day 8 of adulthood. Young worms fed E. coli had short lifespans, no matter what they ate when they were old. Conversely, young worms fed B. subtilis had long lifespans no matter what they ate when they were old. This result indicates that pathogenicity or some other factor associated with E. coli initiates changes in young worms that affect their time of death later on."
CALORIE RESTRICTION AND NITRIC OXIDE
Thursday, May 26, 2011
https://www.fightaging.org/archives/2011/05/calorie-restriction-and-nitric-oxide.php
An open access paper in which researchers delve into the mechanisms of longevity induced through calorie restriction in yeast: "Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. ... . Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan. ... CR-induced NO production may extend lifespan by increasing the stress response (mitohormesis). Our study may have uncovered potential novel components in the CR pathway and provided tools to analyze the interconnections between NO, mitochondrial respiration, CR, and longevity. Although the CR mimics identified in this study share similar NO levels, lifespan, and oxygen consumption phenotypes with CR, they may activate NO production and regulate mitochondrial respiration and lifespan via different mechanisms. It will be enlightening to examine these differences in future studies. Finally, we propose that CR likely confers its beneficial effects via a mitochondria-NO-mediated adaptive metabolic shift, which optimizes metabolism and at the same time improves cellular defense system against the oxidative stress that accumulates with age."
INTEREST IN RADICAL LIFE EXTENSION IN THE MAINSTREAM MEDIA
Wednesday, May 25, 2011
https://www.fightaging.org/archives/2011/05/interest-in-radical-life-extension-in-the-mainstream-media.php
As a sign of changing attitudes amongst run of the mill journalists whose first reaction is to mock everything that isn't widespread knowledge, this is encouraging: "Want to live to be a thousand years old? It's not far-fetched at all if you ask theoretician and geneticist Aubrey de Grey. He believes within the next 25 years there is a 50/50 chance we'll have the technologies to extend human life indefinitely. I learned of Aubrey and his ideas in 2005 and immediately pitched the story to NBC's Today Show. They were intrigued. With the help of correspondent Kerry Sanders and the London bureau, we went out and interviewed Aubrey in a pub in Cambridge. When we finished the story we sent it in to the show. It was promptly killed. Too out there for a mainstream audience. Plus it didn't help that Aubrey looked like Methuselah. Fast forward to 2011 and there Aubrey was in the news again. This time I pitched the story to HDNet's World Report. The program is always looking for stories that deal with interesting issues and are not widely told. This time correspondent Willem Marx met up with Aubrey in a pub in Cambridge and also went punting with him on the Thames River. For my part, I finally got to meet Aubrey at his SENS Foundation laboratory in Mountain View, California. He is tall and wiry and moves like someone with no time to lose. He lovingly strokes the beard which hangs almost to his waist. I asked him if his distinctive look helped or hurt him as he went out in the world trying to win over scientists and venture capitalists to support his work. He said it helped because people looked at him and saw a guy who is not materialistic in the least. It's very clear to them that he is not doing this to get rich. Through his SENS Foundation nonprofit, Aubrey and the scientists who work with him are creating an intersection between research on the biology of aging and regenerative medicine. By doing experiments with the building blocks of cells they hope to someday develop treatments that repair the damage caused by aging, and restore people to a state where they are biologically younger than they were when they started. In other words, people could live out their entire lives as healthy as young adults. Five years ago, the scientific community considered his ideas kind of kooky but now the research is catching up with his theories and Aubrey is gaining credibility. 'This is not science fiction anymore, this is science forseeable,' Aubrey proclaims."
IRON, COPPER, AND BRAIN DNA REPAIR
Wednesday, May 25, 2011
https://www.fightaging.org/archives/2011/05/iron-copper-and-brain-dna-repair.php
A novel view of the mechanisms of neurodegeneration: "o one knows the cause of most cases of Alzheimer's, Parkinson's and other neurodegenerative disorders. But researchers have found that certain factors are consistently associated with these debilitating conditions. One is DNA damage by reactive oxygen species, highly destructive molecules usually formed as a byproduct of cellular respiration. Another is the presence of excessive levels of copper and iron in regions of the brain associated with the particular disorder. ... A high level of copper or iron, they say, can function as a 'double whammy' in the brain by both helping generate large numbers of the DNA-attacking reactive oxygen species and interfering with the machinery of DNA repair that prevents the deleterious consequences of genome damage. ... We don't yet know enough about all the biochemical mechanisms involved, but we have found multiple toxic mechanisms linking elevated iron and copper levels in the brain and extensive DNA damage - pathological features associated with most neurodegenerative disorders. ... some people's tissues contain much larger quantities of iron or copper, which overwhelm the proteins that normally bind the metals and sequester them for safe storage. The result: so-called 'free' iron or copper ions, circulating in the blood and able to initiate chemical reactions that produce reactive oxygen species. Reactive oxygen species cause the majority of the brain cell DNA damage that we see in Alzheimer's and Parkinson's disease, as well as most other neurodegenerative disorders."
A REVIEW AND APPRAISAL OF THE ROLE OF DNA DAMAGE IN AGING
Tuesday, May 24, 2011
https://www.fightaging.org/archives/2011/05/a-review-and-appraisal-of-the-role-of-dna-damage-in-aging.php
A review paper: "Given the central role of DNA in life, and how ageing can be seen as the gradual and irreversible breakdown of living systems, the idea that damage to the DNA is the crucial cause of ageing remains a powerful one. DNA damage and mutations of different types clearly accumulate with age in mammalian tissues. Human progeroid syndromes resulting in what appears to be accelerated ageing have been linked to defects in DNA repair or processing, suggesting that elevated levels of DNA damage can accelerate physiological decline and the development of age-related diseases not limited to cancer. Higher DNA damage may trigger cellular signalling pathways, such as apoptosis, that result in a faster depletion of stem cells, which in turn contributes to accelerated ageing. Genetic manipulations of DNA repair pathways in mice further strengthen this view and also indicate that disruption of specific [repair pathways] is more strongly associated with premature ageing phenotypes. Delaying ageing in mice by decreasing levels of DNA damage, however, has not been achieved yet, perhaps due to the complexity inherent to DNA repair and DNA damage response pathways. Another open question is whether DNA repair optimization is involved in the evolution of species longevity, and we suggest that the way cells from different organisms respond to DNA damage may be crucial in species differences in ageing. Taken together, the data suggest a major role of DNA damage in the modulation of longevity, possibly through effects on cell dysfunction and loss, although understanding how to modify DNA damage repair and response systems to delay ageing remains a crucial challenge."
THE NEXT STEP IN THE STUDY OF LONGEVITY IN ASHKENAZI JEWS
Tuesday, May 24, 2011
https://www.fightaging.org/archives/2011/05/the-next-step-in-the-study-of-longevity-in-ashkenazi-jews.php
The topic of study moves from genes to stem cells: "Scientists at Cornell Medical College in New York are due to begin to study the stem cells of almost a dozen Ashkenazi Jews, who were a heavily persecuted group which originated from Russia. Experts believe that years of intermarriage - and the sharing of genetic traits - might have helped the group live for so long. In an attempt to find out how they live such long lives, research will be performed on the heart, lung, liver and other cells. .. The reason they live so long is not because they live healthy lives. Interbreeding can have a negative impact, but, in this case, some families had the opposite effect. They don't get cardiovascular disease, cancer, neurodegeneration or diabetes or very low rates. And we believe that one aspect to their resistance to disease has a stem-cell base. ... will extract stem cells from the elderly Jews' blood before transforming them into the cells of some vital organs ... The cells which have been engineered will then undergo stress tests, and then they will be assessed to see how they fared."
PRODUCING ASTROCYTES TO ORDER
Monday, May 23, 2011
https://www.fightaging.org/archives/2011/05/producing-astrocytes-to-order.php
Another cell type is added to the list of those that can be produced on demand in the laboratory: "Pity the lowly astrocyte, the most common cell in the human nervous system. Long considered to be little more than putty in the brain and spinal cord, the star-shaped astrocyte has found new respect among neuroscientists who have begun to recognize its many functions in the brain, not to mention its role in a range of disorders of the central nervous system. [Now] a group [reports] it has been able to direct embryonic and induced human stem cells to become astrocytes in the lab dish. The ability to make large, uniform batches of astrocytes [opens] a new avenue to more fully understanding the functional roles of the brain's most commonplace cell, as well as its involvement in a host of central nervous system disorders ranging from headaches to dementia. What's more, the ability to culture the cells gives researchers a powerful tool to devise new therapies and drugs for neurological disorders. ... Not a lot of attention has been paid to these cells because human astrocytes have been hard to get. But we can make billions or trillions of them from a single stem cell. Without the astrocyte, neurons can't function. Astrocytes wrap around nerve cells to protect them and keep them healthy. They participate in virtually every function or disorder of the brain. ... They could be used as screens to identify new drugs for treating diseases of the brain, they can be used to model disease in the lab dish and, in the more distant future, it may be possible to transplant the cells to treat a variety of neurological conditions, including brain trauma, Parkinson's disease and spinal cord injury. It is possible that astrocytes prepared for clinical use could be among the first cells transplanted to intervene in a neurological condition as the motor neurons affected by the fatal amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, are swathed in astrocytes."
SPURRING NEUROGENESIS IN THE LIVING BRAIN
Monday, May 23, 2011
https://www.fightaging.org/archives/2011/05/spurring-neurogenesis-in-the-living-brain.php
Researchers here demonstrate a method of adjusting the pace at which nerve cells in the brain are created, and suggest that it might work on other cell types in the body: "Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)-cyclinD1 complex in the adult mouse hippocampus cell autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4-cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells."
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