FIGHT AGING! NEWSLETTER
August 8th 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!
- A Profile of Sierra Sciences and Their Work on Telomeres
- Genetics, Long Lives, and Bad Lifestyles
- The Influence of Gut Bacteria
- Latest Headlines from Fight Aging!
A PROFILE OF SIERRA SCIENCES AND THEIR WORK ON TELOMERES
Sierra Sciences has been around for a number of years, one of a small number of commercial research groups searching for a clinical application relating to telomere length:
"A recent long Popular Science article looks at Sierra Sciences and its founder, a group that has been working on telomere biology and its role in aging for some years. Alongside a number of other research groups, the Sierra crowd believe that telomeres are a lynchpin portion of our biochemistry and manipulating them might significantly extend life. ... Telomeres, you might recall, are the frayed ends of our chromosomes, there in order to prevent problems during cellular replication - though more correctly they might be thought of as one portion of a more complex and regulated system that touches upon many cellular processes.
"The bottom line for me is that this is certainly a line of research worth chasing further - there are a range of experiments that show benefits from telomerase therapies, such as improved immune system function, for example. But is the telomeres, or is it something else that's the important underlying mechanism? Either way, Sierra Sciences ran out of money for research in the end and now seems to be removing itself from the game through a mechanism we've sadly seen before, which is to get into bed with the supplement industry. I cannot think of a small company that has done this and remained a serious contender in advancing the state of medical science - the end result more often looks like the protandim debacle, in which whatever interesting scientific work once existed is abandoned and its echoes used to promote herbal compounds sold with a garnishing of lies."
GENES, LONG LIVES, AND BAD LIFESTYLES
Researchers have recently argued that genetic differences in long-lived populations act as a buffer to somewhat protect against the consequences of bad lifestyle choices, and this is the mechanism by which these populations have a higher life expectancy as a whole:
"Many of the worlds longest-lived people became the world's longest-lived people despite a history of what are considered to be poor lifestyle choices from the perspective of long term health. Amongst their number are smokers, the overweight, and the sedentary - all items shown to cause great harm to health in the long term. Studies have shown that each of these considered in isolation can shave as much as a decade from your life expectancy, and that's quite aside from what they will do to your quality of life via an increased risk of suffering chronic and debilitating medical conditions. So how is it that we see a fair proportion of extremely old people with such a poor track record for basic good health choices over the course of their lives?"
THE INFLUENCE OF GUT BACTERIA
The bacteria we carry with us play an important role in the operation of our metabolism - and thus, now that researchers are looking into the manipulation of metabolism to slow aging, they are also beginning to consider what could be achieved by targeting these bacterial populations:
"On the basis of recent knowledge in worms, flies, and humans, an important role of the gut microbiota in aging and longevity is emerging. The complex bacterial community that populates the gut and that represents an evolutionary adapted ecosystem correlated with nutrition appears to limit the accumulation of pathobionts and infections in all taxa, being able of affecting the efficiency of the host immune system and exerting systemic metabolic effects. There is an urgent need to disentangle the underpinning molecular mechanisms, which could shed light on the basic mechanisms of aging in an ecological perspective. Thus, it appears possible to extend healthy aging and lifespan by targeting the host as a metaorganism by manipulating the complex symbiotic ecosystem of gut microbiota, as well as other possible ecosystems of the body."
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!
LATEST HEADLINES FROM FIGHT AGING!
SKIN CELLS TURNED INTO BRAIN CELLS
Friday, August 5, 2011
Another step forward for the field of regenerative medicine: researchers have "discovered a novel way to convert human skin cells into brain cells ... Rather than using models made in yeast, flies or mice for disease research, all cell-reprogramming technology allows human brain, heart and other cells to be created from the skin cells of patients with a specific disease. The new cells created from the skin cells contain a complete set of the genes that resulted in that disease - representing the potential of a far-superior human model for studying illnesses, drugs and other treatments. In the future, such reprogrammed skin cells could be used to test both drug safety and efficacy for an individual patient with, for example, Alzheimer's disease. ... This technology should allow us to very rapidly model neurodegenerative diseases in a dish by making nerve cells from individual patients in just a matter of days - rather than the months required previously. ... used two genes and a microRNA to convert a skin sample from a 55-year-old woman directly into brain cells. (MicroRNAs are tiny strands of genetic material that regulate almost every process in every cell of the body.) The cells created [exchanged] the electrical impulses necessary for brain cells to communicate ... Using microRNA to reprogram cells is a safer and more efficient way than using the more common gene-modification approach. In ensuing experiments, [the researchers hope] to rely only on microRNAs and pharmaceutical compounds to convert skin cells to brain cells, which should lead to more efficient generation of cells for testing and regenerative purposes."
AN INTERVIEW WITH LAURA DEMING
Friday, August 5, 2011
An interview with one of the Thiel Fellows: "The goal is to extend the healthy human lifespan. In the past couple of decades, we've learned a lot about the basic science of aging. Now it's time to start translating the basic science into marketable therapies. I want to find and fund the projects creating those therapies. ... When I was eight, my mom told me about death and I couldn't stop crying for days. What a tragedy! Life is incredible, but death is inevitable. I already knew biology was fantastic fun. But that moment, for me, made science more than fun. It made it into a power that could save lives. And I couldn't imagine doing something more fascinating or important. ... When I was twelve, I was lucky enough to meet Cynthia Kenyon (biogerontologist and molecular biologist), who is a pioneer in the field of anti-aging research. She is amazing. I ended up working in her lab, at the University of California San Francisco, for a few years. She had a way of describing scientists as detectives, trying to solve mysteries and catch genetic culprits. Growing up at UCSF, getting to tinker with tiny worms in a biology lab and sit in on classes about genetics and biochemistry ... that was an incredible experience. ... Anti-aging is such an important field, but it is underfunded. Building business around an anti-aging therapy is no mean feat, especially when the FDA does not recognize aging as a disease. The goal here is to create a profitable, self-sustaining structure that will fund a portfolio of anti-aging projects, and then commercialize the research. It will be important that scientists get a stable source of funding for long-term lifespan projects, and a cut of the revenue from the projects they create."
CALCIUM CHANNELS AND AGING MUSCLES
Thursday, August 4, 2011
Via EurekAlert!: "There is a reason exercise becomes more difficult with age. [Research] ties the weakness of aging to leaky calcium channels inside muscle cells. But there is some good news: the researchers say a drug already in Phase II clinical trials for the treatment of heart failure might plug those leaks. Earlier studies [showed] the same leaks underlie the weakness and fatigue that come with heart failure and Duchenne muscular dystrophy. ... It's interesting, normal people essentially acquire a form of muscular dystrophy with age. The basis for muscle weakness is the same. ... Extreme exercise like that done by marathon runners also springs the same sort of leaks, [but] in that case damaged muscles return to normal after a few days of rest. ... The leaks occur in a calcium release channel called ryanodine receptor 1 (RyR1) that is required for muscles to contract. Under conditions of stress, those channels are chemically modified and lose a stabilizing subunit known as calstabin1. ... Calcium inside of muscle cells is usually kept contained. When it is allowed to leak out into the cell that calcium itself is toxic, turning on an enzyme that chews up muscle cells. Once the leak starts, it's a vicious cycle. The calcium leak raises levels of damaging reactive oxygen species, which oxidize RyR1 and worsen the leak. The researchers made their discovery by studying the skeletal muscles of young and old mice. They also showed that 6-month-old mice carrying a mutation that made their RyR1 channels leaky showed the same muscular defects and weakness characteristic of older mice. When older mice were treated with a drug known as S107, the calcium leak in their muscles slowed and the animals voluntarily showed about a 50 percent increase in the amount of time spent wheel running. Now in clinical trials for patients with heart failure, the drug is known to work by restoring the connection between costabilin and RyR1."
ON THE WAY TO BLOOD ON DEMAND
Thursday, August 4, 2011
Singularity Hub here looks at some of the research work that will lead to the ability to generate blood as needed: "Researchers [have] found a way to hunt down and isolate the stem cells from which your entire blood supply is derived. Until now, these hematopoietic stem cells (HSC) have been remarkably hard to track and isolate ... researchers were able to identify the CD49f protein as a key surface marker for hemotopoietic stem cells. Single CD49f HSCs were placed inside immunosupressed mice, and monitored to see how they developed. The entire spectrum of blood cells were produced, and just as important: they were self-renewing. The CD49f HSC wasn't just creating blood, it was creating an expanding and sustaining blood supply that should theoretically survive long term in the body." This will lead to a number of potential ways to generate sufficient quantities of blood to remove the need for blood donations, and ultimately will allow a patient's own cells to be used to generate blood on demand.
THE DOUBLE STANDARD
Wednesday, August 3, 2011
Depressed Metabolism here notes the existence of a double standard when it comes to the science and practice of cryonics - actually one you'll find exists for all serious endeavors in life extension, such as SENS research: "One of the most predictable features of public debates about cryonics is that those arguing in favor of cryonics are held to more rigorous standards than those seeking conventional medical treatment. Advocates of cryonics do not just have to prove that cryonics will work, they are also supposed to solve problems like overpopulation and the presumed boredom arising from expended lifespans. To some, people who make cryonics arrangements have an inflated perception of their own importance and should just forgo such selfish attempts to extend their lives. The default position seems to be that people should not exist and that life needs justification. Could you imagine such antinatalist rhetoric being employed when a person seeks conventional medical treatment to extend their life? We can't, and such responses are quite indicative of the fact that people are not interested in serious evaluation of the cryonics argument."
OSTEOPOROSIS AND AGE-RELATED STEM CELL ALTERATIONS
Wednesday, August 3, 2011
Changes in stem cell biology and capabilities are considered important in age-related degeneration. For example: "A decline in cellular homeostasis in older individuals underlies age-related pathologies like osteoporosis and osteoarthritis. [Researchers] report key differences in the patterns of expressed mRNAs in bone-marrow mesenchymal stem cells (bmMSCs) of young donors compared with old human donors. The distinct subsets of expressed genes associated with glycobiology are consistent with the underlying age-related decline in bone marrow function. ... It is now well established that in older individuals stem cells can become 'aged' and thus incapable of renewing surrounding tissues and organs as efficiently as young individuals. Experimental and clinical evidence has revealed the importance of stem cell aging in bone marrow transplants, as recipients of bone marrow from older donors do not fare as well as recipients of bone marrow from younger donors. However, the molecular mechanisms governing stem cell aging are not well understood. An important first step towards this goal is to delineate the gene expression differences between stem cells from young and old individuals. Bone marrow stem cells are particularly well suited for such studies, as they are relatively easy to purify to homogeneity. ... bmMSCs showed age-increases in the expression of genes associated with the degradation of N-glycans and glycosaminoglycans and with the biosynthesis of glycosphingolipids. These results reveal major differences in the glycobiology and glycan compostion of young and old bmMSCs, associated with age-related changes in the cellular responses to autocrine and paracrine signals. The difference in glycan pathways may not be limited to bmMSCs or even to stem cells, but could be more widely prevalent among other cell types."
MORE TINKERING WITH IGF-1
Tuesday, August 2, 2011
IGF-1 can be manipulated to alter species longevity, and here researchers are starting to try tissue-specific alterations rather than global alterations: "Transgenic mice with low levels of global insulin-like growth factor-I (IGF-I) throughout their life span, including pre- and postnatal development, have increased longevity. This study investigated whether specific deficiency of liver-derived, endocrine IGF-I is of importance for life span. ... Liver-specific inactivation of the IGF-I gene was induced in mice at one month of age in most experiments. However, food intake, body composition, oxygen consumption at rest, and activity level were measured in mice that underwent inactivation of liver-derived IGF-I at 12 months of age. ... Serum IGF-I was reduced by approximately 80% in mice with adult, liver-specific IGF-I inactivation (LI-IGF-I-/- mice), and body weight decreased due to reduced body fat. The mean life span of LI-IGF-I-/- mice increased 10% vs. control mice ... Body weight and body fat decreased in LI-IGF-I-/- mice, possibly due to increased energy expenditure during exercise. Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms that could underlie the increased mean life span in the LI-IGF-I-/- mice."
NANOFIBERS TO SPUR BLOOD VESSEL REGENERATION
Tuesday, August 2, 2011
From the MIT Technology Review: researchers "developed a liquid that, when injected into patients, forms a matrix of loosely tangled nanofibers. Each of these fibers is covered in microscopic protuberances that mimic vascular endothelial growth factor, or VEGF - a protein that occurs naturally in the body and causes chemical reactions that result in the growth of new blood vessels. By mimicking VEGF, the nanofiber has the same biological effect. ... Tissue engineers have tried using VEGF itself to stimulate the growth of blood vessels, but clinical trials with the protein were unsuccessful ... This is because VEGF tends to diffuse out of the target tissue before it can do its job. Maintaining a therapeutic concentration in the target tissue would require a series of expensive, invasive injections. The new nanomaterial has a similar effect, but it lasts much longer, and is completely biodegradable once its job is finished. ... The researchers tested their material in mice. The blood supply to the animals' hind legs was restricted. Left untreated, these limbs would die. The nanofiber treatment rescued the limbs, and resulted in better motor function and blood circulation than the other treatments, including a treatment with VEGF. ... there could be more uses for nanofibers that mimic proteins from the body. For example, they could be used to stimulate the formation of connective tissues such as bone and cartilage, or to regenerate neurons in the brain."
THE INTERNATIONAL AGING RESEARCH PORTFOLIO OUTLINED
Monday, August 1, 2011
An open access paper on the goals and structure of the International Aging Research Portfolio: "Aging and age-related disease represents a substantial quantity of current natural, social and behavioral science research efforts. Presently, no centralized system exists for tracking aging research projects across numerous research disciplines. The multidisciplinary nature of this research complicates the understanding of underlying project categories, the establishment of project relations, and the development of a unified project classification scheme. We have developed a highly visual database, the International Aging Research Portfolio (IARP), available at AgingPortfolio.org to address this issue. The database integrates information on research grants, peer-reviewed publications, and issued patent applications from multiple sources. Additionally, the database uses flexible project classification mechanisms and tools for analyzing project associations and trends. This system enables scientists to search the centralized project database, to classify and categorize aging projects, and to analyze the funding aspects across multiple research disciplines. The IARP is designed to provide improved allocation and prioritization of scarce research funding, to reduce project overlap and improve scientific collaboration thereby accelerating scientific and medical progress in a rapidly growing area of research. Grant applications often precede publications and some grants do not result in publications, thus, this system provides utility to investigate an earlier and broader view on research activity in many research disciplines."
EXERCISE AND SARCOPENIA
Monday, August 1, 2011
Sarcopenia is the name given to age-related loss of muscle mass and strength. Here is a review paper on the current state of knowledge regarding exercise as a way to slow the onset of sarcopenia: "Numerous studies have demonstrated that the etiology of sarcopenia is multi-causal and very complex process. The degradation of muscle mass leads to a loss of strength, later on to a decreased functional status, impaired mobility, a higher risk of falls, and eventually an increased risk of mortality. Present guidelines state that physical inactivity or a decreased physical activity level is a part of the underlying mechanisms of sarcopenia and therefore physical activity can be seen as an important factor to reverse or modify the development of sarcopenia. ... Results in the area of physical activity and aging have not always been homogeneous. The inconsistent findings in this research area are related to the different understanding of terms and underlying constructs along with different population, type of intervention, or measurement methods. ... With regard to the formulated future role of physical activity this article will discuss in addition different barriers and challenges in the prevention and treatment of sarcopenia. A multitude of studies shows that structured exercise programs including progressive resistance or power training have positive effects on sarcopenia and sarcopenia-related outcomes but less or inconclusive information is available for the transfer to functional outcomes. ... Both physical activities and exercise have shown to decrease risk of sarcopenia and onset of functional limitations in older persons. Unfortunately the cohort of older persons is the one with the highest percentage of individuals classified as inactive or sedentary. Therefore motivating older persons to increase their physical activity level as well as providing safe access to exercise programs seems to be a mandatory task."