Fight Aging! Newsletter, January 2nd 2012

January 2nd 2012

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!



- A Look Back at 2011
- SENS Foundation Year End Appeal
- Methuselah Foundation Focuses on the New Organ Mprize
- Needed: A Robust Way to Identify Senescent Cells
- The Black Market in Medical Progress
- Discussion
- Latest Headlines from Fight Aging!


It has been an interesting year, and I suppose it is traditional at the tail end of December to cast a thoughtful eye back at the highlights. Follow the link below for a brief overview of the year's highlights, promising new research, and happenings in the longevity science community:


Well, the timing didn't quite work out on this making its way into the newsletter before the new year - but it doesn't really matter when you decide to donate to help fund research into rejuvenation biotechnology. The money will do just as much good in January as it will do in December:

"The diseases of aging - heart disease, Alzheimer's, macular degeneration - are not only terrible, tragic, and debilitating, but potentially preventable. SENS Foundation is working to use regenerative medicine to repair the cellular and molecular damage that accumulates in all of our bodies over time. With the right application of such treatments, we could slow, or even reverse, the pathology of aging. We call these innovative, damage-repairing treatments rejuvenation biotechnologies. In human and economic terms, their successful development would represent an incredible victory. And yet, research into rejuvenation biotechnologies has received virtually no public funding. SENS Foundation has yet to receive monetary support from any government body. Other organizations in the field are in a similar position - the Mayo Clinic, for instance, was recently denied funding by the NIH for follow-up work on its landmark senescent cell study published in Nature. If rejuvenation biotechnologies are to be developed, private donors will need to step forward. SENS Foundation has led, and continues to lead, the charge towards robust therapies that address the diseases of aging."


The Methuselah Foundation is running a pledge drive in the first months of 2012, focused on the New Organ Mprize:

"So what is the Methuselah Foundation up to these days? As you might know, the Foundation has administered the Mprize for longevity science since 2003: a multi-million dollar prize fund that encourages researchers to find ways to extend healthy life in mice - a good marker for technologies that may then be applicable to other mammals, such as we humans. Last year, the Foundation inaugurated a new prize, the NewOrgan prize that aims to spur greater progress in tissue engineering and the creation of functional new organs from a patient's own cells. This dovetails with the Foundation's investment strategy: helping to fund companies that focus on advanced tissue engineering, such as Organovo, and solving organ transplant issues, such as Silverstone Solutions. The Methuselah Foundation sent out a sneak peek email yesterday with a pointer to the New Organ Mprize website and the first pledge drive with matching funds: this will be the big thing for the coming year."


With the recent demonstration of health and longevity benefits in mice resulting from the selective destruction of senescent cells, we should expect renewed interest in how to reliably identify those cells:

"This entire portion of the basis for degenerative aging could be removed with a therapy that destroyed senescent cells sufficiently well. This is why the earlier mentioned demonstration of senescent cell destruction - and corresponding health benefits - in mice was a welcome advance. Unfortunately, the method used was based on some clever genetic engineering and while effective at eliminating senescent cells without harming other cells in the engineered mouse breed, it has little direct application to the development of human clinical medicine.

"Meanwhile, the cancer and immunotherapy research communities are making great strides in developing many forms of nanoscale technology that can be coupled to a sensor and sent to destroy those cells that the sensor reacts with - and without harming any other nearby cells. Researchers have used nanoparticles, antibodies, viruses, and bacteria to home in on cells with specific surface markers or other characteristics, and there deliver some form of killing blow. The trick here is not so much the killing blow, as many of the successful demonstrations of targeted cancer cell destruction did no more than deliver old-style chemotherapy drugs - just in very small doses and on a cell-by-cell basis rather than flooding the whole body. That works very well to minimize side-effects and maximize harm to the cancer.

"The point of this sidebar is that these technology platforms could be quickly repurposed to attack senescent cells, but only when there emerges a robust way of distinguishing between senescent and non-senescent cells."


When medical progress is made illegal, then there will be a black market in medical progress. Sadly, the FDA has indeed made vast swathes of medical development illegal, thanks to its oppressive system of regulation. One symptom of this is a complete absence of medical procedures that would exist in an open, competitive marketplace. Another symptom is the prosecution of people who try to organize stem cell therapies:

"This is the standard situation: when regulation makes it impossible to meet demand or to try to develop and offer meaningful products, a black market will arise. That market will be less transparent, more costly, and less effective at delivering quality products than a free market would be in the absence of regulation. A black market will also tend to attract a larger contingent of sellers willing to commit fraud than would otherwise be the case, as the buyers have lower chances of success in any legal action or other means of forcing restitution.

"So these [latest fellows to be prosecuted by the FDA] may be frauds, or they may be legitimate businesspeople trying to operate a medical tourism business, offering services that are perfectly legal - and even admirable - outside the US, while within the US forthright invention and competition in medicine is pretty much forbidden. Either way, other would-be legitimate businesspeople are going to look at this and think twice about trying to make the world a better place by offering better medical services."


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 30, 2011
In aging there is a lot of correlation - many biological systems that are traditionally studied separately are declining at once, so most researchers are only looking in detail at one tiny part of aging. Part of the challenging facing researchers has always been how to figure out what is cause and what is consequence given the need for specialization to make progress in any given small area of the biology of aging. Here, researchers focus on the immune system, and you can see the biases inherent in being a specialist: "The aging process is accompanied by an impairment of the physiological systems including the immune system. This system is an excellent indicator of health. We have also observed that several functions of the immune cells are good markers of biological age and predictors of longevity. In agreement with the oxidation-inflammation theory that we have proposed, the chronic oxidative stress that appears with age affects all cells and especially those of the regulatory systems, such as the nervous, endocrine and immune systems and the communication between them. This fact prevents an adequate homeostasis and, therefore, the preservation of health. We have also proposed an involvement of the immune system in the aging process of the organism, concretely in the rate of aging, since there is a relation between the redox state and functional capacity of the immune cells and the longevity of individuals. A confirmation of the central role of the immune system in oxi-inflamm-aging is that several lifestyle strategies such as the administration of adequate amounts of antioxidants in the diet, physical exercise, physical and mental activity through environmental enrichment and hormetic interventions improve functions of immune cells, decreasing their oxidative stress, and consequently increasing the longevity of individuals."

Friday, December 30, 2011
Pulling together the connections in a review paper: "Obesity is a condition in which excess or abnormal fat accumulation may present with adverse effects on health and decreased life expectancy. Increased body weight and adipose tissue accumulation amplifies the risk of developing various age-related diseases, such as cardiovascular disease, Type 2 Diabetes Mellitus, musculoskeletal disorders, respiratory diseases and certain types of cancer. This imbalance in body composition and body weight is now recognized as a state of increased oxidative stress and inflammation for the organism. Increasing oxidative stress and inflammation affect telomeres. Telomeres are specialized DNA-protein structures found at the ends of eukaryotic chromosomes and serve as markers of biological aging rate. They also play a critical role in maintaining genomic integrity and are involved in age-related metabolic dysfunction. Erosion of telomeres is hazardous to healthy cells, as it is a known mechanism of premature cellular senescence and loss of longevity. The association of telomeres and oxidative stress is evident in cultured somatic cells in vitro, where oxidative stress enhances the process of erosion with each cycle of replication. Shorter telomeres have been associated with increasing body mass index, increased adiposity, and more recently with increasing waist to hip ratio and visceral excess fat accumulation. Furthermore, many of the metabolic imbalances of obesity (e.g. glycemic, lipidemic, etc.) give rise to organ dysfunction in a way that resembles the accelerated aging process."

Thursday, December 29, 2011
A commentary at the journal Aging: "In the past 15 years, genomics has penetrated all areas of the life sciences, and this dramatic change in the way science is done is often viewed as genome revolution. However, application of genomics to study senescence and aging lagged behind. Until this year, no genomes have been sequenced explicitly to understand aging. In this regard, the recent completion of the genome of the naked mole rat marks an important milestone, as this study was performed primarily to better understand the exceptional longevity of this rodent. Naked mole rats live in the subterranean niche in southeast Africa and are the longest-lived rodents (maximum lifespan of 32 years). Being the size of a mouse, naked mole rats can be conveniently studied in the laboratory setting and compared with other rodents. What have we learned from the initial analysis of the genome of this remarkable animal? First, the genome is characterized by the reduced level of polymorphism, consistent with low DNA mutation rate (although other explanations are also possible). Second, an unusual thermogenesis of naked mole rats, which may be linked to longevity through metabolic rate, is consistent with the altered sequence of a key thermoregulator, UCP1, which modified its sequences that mediate regulation by nucleotides and fatty acids. Another interesting finding is the unique sequence of a tumor suppressor p16, a protein whose mutations were linked to a variety of human diseases associated with aging. In addition, analyses of gene expression as a function of age distinguished naked mole rats from other mammals. ... The availability of the genome of the naked mole rat should be viewed as the first step in the process of understanding of the delayed aging of this mammal, and also as a useful resource for studying the aging process in general. It is clear that much of its value lies in comparison with the genomes of other mammals, both with long and short lifespans, as well as in downstream functional genomic studies that assess genetic and epigenetic regulation networks. Comparative genomics of short-lived and long-lived organisms offers great opportunities to understand evolutionary forces and molecular mechanisms that regulate lifespan."

Thursday, December 29, 2011
Human studies may reveal a correlation between longevity and lower rates of reproduction: "A number of leading theories of aging, namely The Antagonistic Pleiotropy Theory (Williams, 1957), The Disposable Soma Theory (Kirkwood, 1977) and most recently The Reproductive-Cell Cycle Theory (Bowen and Atwood, 2004, 2010) suggest a tradeoff between longevity and reproduction. While there has been an abundance of data linking longevity with reduced fertility in lower life forms, human data have been conflicting. We assessed this tradeoff in a cohort of genetically and socially homogenous Ashkenazi Jewish centenarians (average age ~100 years). As compared with an Ashkenazi cohort without exceptional longevity, our centenarians had fewer children (2.01 vs 2.53, p<0.0001), were older at first childbirth (28.0 vs 25.6, p<0.0001), and at last childbirth (32.4 vs 30.3, p<0.0001). The smaller number of children was observed for male and female centenarians alike. The lower number of children in both genders together with the pattern of delayed reproductive maturity is suggestive of constitutional factors that might enhance human life span at the expense of reduced reproductive ability."

Wednesday, December 28, 2011
A recent paper: "Birds generally age slower and live longer than similar sized mammals. For birds this occurs despite elevated blood glucose levels that for mammals would in part define them as diabetic. However these data were acquired in respiration states that have little resemblance to conditions in healthy tissues and mitochondrial [reactive oxygen species] production is probably minimal in healthy animals. Indeed mitochondria probably act as net consumers rather than producers of [reactive oxygen species]. Here we propose that (1) if mitochondria are antioxidant systems, the greater mitochondrial mass in athletic species, such as birds, is advantageous as it should provide a substantial sink for [reactive oxygen species]. (2) The intense drive for aerobic performance and decreased body density to facilitate flight may explain the relative insensitivity of birds to insulin, as well as depressed insulin levels and apparent sensitization to glucagon. Glucagon also associates with the sirtuin protein family, most of which are associated with caloric restriction regulated pathways, mitochondrial biogenesis and life span extension. (3) We note that telomeres, which appear to be unusually long in birds, bind Sirtuins 2 and 4 and therefore may stabilize and protect nuclear DNA. Ultimately these flight driven responses may suppress somatic growth and protect DNA from oxidative damage that would otherwise lead to ageing and non-viral cancers."

Wednesday, December 28, 2011
Here is another of the many theories aiming to explain why women live longer than men: "One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels. Our results show that physiological concentrations of estrogens activate estrogen receptors and the MAPK and NFKB pathway. Activation of NFkB by estrogens subsequently activates the expression of Mn-SOD and GPx. Moreover, we have demonstrated that genistein, the most abundant phytoestrogen in soya, reproduces the antioxidant effect of estradiol at nutritionally relevant concentrations by the same mechanism ... We conclude that estrogens and phytoestrogens up-regulate expression of antioxidant enzymes via the estrogen receptor and MAPK activation, which in turn activate the NFkB signalling pathway, resulting in the up-regulation of the expression of longevity-related genes."

Tuesday, December 27, 2011
One of the predictions of reliability theory is that individual life expectancy has a fair dependency on very early life development and circumstances: we are all born with different initial levels of biological damage at the cellular and molecular level, and that damage matters in the long term. Data suggesting that birth month influences life expectancy can be lumped in with possible solar radiation effects as supporting evidence: "This study explores the effects of month of birth (a proxy for early-life environmental influences) on the chances of survival to age 100. Months of birth for 1,574 validated centenarians born in the United States in 1880-1895 were compared to the same information obtained for centenarians' 10,885 shorter-lived siblings and 1,083 spouses. Comparison was conducted using a within-family analysis by the method of conditional logistic regression, which allows researchers to control for unobserved shared childhood or adulthood environment and common genetic background. It was found that months of birth have significant long-lasting effect on survival to age 100: siblings born in September-November have higher odds to become centenarians compared to siblings born in March. A similar month-of-birth pattern was found for centenarian spouses. These results support the idea of early-life programming of human aging and longevity."

Tuesday, December 27, 2011
An immunotherapy approach is turned to treating autoimmune conditions: scientists have "turned the tables on an autoimmune disease. In such diseases, including Crohn's and rheumatoid arthritis, the immune system mistakenly attacks the body's tissues. But the scientists managed to trick the immune systems of mice into targeting one of the body's players in autoimmune processes, an enzyme known as MMP9. ... [Researchers] have spent years looking for ways to home in on and block members of the matrix metalloproteinase (MMP) enzyme family. These proteins cut through such support materials in our bodies as collagen, which makes them crucial for cellular mobilization, proliferation and wound healing, among other things. But when some members of the family, especially MMP9, get out of control, they can aid and abet autoimmune disease and cancer metastasis. Blocking these proteins might lead to effective treatments for a number of diseases. ... rather than attempting to design a synthetic molecule to directly attack MMPs [an] MMP immunization would trick the body into creating antibodies that block the enzyme at its active site. [Researchers] created an artificial version of the metal zinc-histidine complex at the heart of the MMP9 active site. They then injected these small, synthetic molecules into mice and afterward checked the mice's blood for signs of immune activity against the MMPs. ... when they had induced an inflammatory condition that mimics Crohn's disease in mice, the symptoms were prevented when mice were treated with [the new synthetic molecules]. We are excited not only by the potential of this method to treat Crohn's, [but] by the potential of using this approach to explore novel treatments for many other diseases."

Monday, December 26, 2011
Researchers here use simple measures of cognitive function to look at differential rates of aging between regions and populations: "Comparing the burden of aging across countries hinges on the availability of valid and comparable indicators. The Old Age Dependency Ratio allows only a limited assessment of the challenges of aging, because it does not include information on any individual characteristics except age itself. Existing alternative indicators based on health or economic activity suffer from measurement and comparability problems. We propose an indicator based on age variation in cognitive functioning. We use newly released data from standardized tests of seniors' cognitive abilities for countries from different world regions. In the wake of long-term advances in countries' industrial composition, and technological advances, the ability to handle new job procedures is now of high and growing importance, which increases the importance of cognition for work performance over time. In several countries with older populations, we find better cognitive performance on the part of populations aged 50+ than in countries with chronologically younger populations. This variation in cognitive functioning levels may be explained by the fact that seniors in some regions of the world experienced better conditions during childhood and adult life, including nutrition, duration and quality of schooling, lower exposure to disease, and physical and social activity patterns." This might best be viewed in the context of reliability theory: if we consider aging and cognitive function as outcomes based on accumulation of damage within the system of the body and brain, then we would expect that people with lower levels of damage will tend to be more robust and capable.

Monday, December 26, 2011
Significant loss of the senses of smell and taste, a condition known as anosmia, can occur with aging. Here, researchers investigate stem cell related mechanisms; this may be another case of functionality fading because the stem cell population necessary to support it is shutting down with advancing age: "Experts estimate that about 2 percent of the U.S. population suffers from [a] lack of smell known as anosmia. And research by neuroscientists [provides] hope of new therapies for those who have lost their sense of smell, whether due to aging, trauma or a viral infection. In the study published this month [the researchers found] a genetic trigger responsible for renewing smell sensors in the nose. That gene, known as p63, tells olfactory stem cells whether to replace themselves or to change into different types of cells. Under normal circumstances [there] is a balance between the two outcomes. But when p63 is absent, the cells only turn into other types of mature cells, which [could] eventually lead to the complete depletion of olfactory cells. One reason for the onset of anosmia could be that the stem cells age and are less able to regenerate, or they are just depleted. Finding a way to promote stem cell renewal could help maintain sensory functions, such as the sense of smell."



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