FIGHT AGING! NEWSLETTER
August 29th 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!
- An Interesting Issue of Life Extension Magazine
- The Folly of Dietary Overengineering
- How Far Can Boosted Autophagy Take Us?
- Latest Headlines from Fight Aging!
AN INTERESTING ISSUE OF LIFE EXTENSION MAGAZINE
The Life Extension Foundation, essentially a supplement shop, has become more involved in funding and advocating modern longevity science in recent years. The latest issue of their in-house magazine contains a number of articles that might be of interest to Fight Aging! readers:
"The latest issue of Life Extension Magazine is fairly focused on the long view, and taken as a whole is a more than usually explicit call for the defeat of aging through research and development of the appropriate biotechnology. It is my sense that the mouthpiece of that organization has been steering more towards that direction in recent years, and I'm pleased to see it - the less the LEF folk conduct themselves as a standard issue supplement shop and the more they conduct themselves as a source of advocacy and funding for serious longevity research (such as SENS) the better they look to my eyes. ... I will be interested to see how well this initiative proceeds; the LEF has a broad base of customers and readers, and it will be informative to see just how many of them can be converted from the mindset of supplement purchaser to the mindset of supporter of meaningful longevity science. There is a large gap between those two points on the cultural map."
THE FOLLY OF DIETARY OVERENGINEERING
Some thoughts the level of effort you might put in to optimizing your diet:
"Diets are like cars; we all deal with them, and up to a certain point the more you know the more you'll get out of them. That certain point is actually a pretty low threshold of knowledge in either case - but you wouldn't know it from the vast literature and ongoing conversations on tinkering with cars or tinkering with diet. ... Optimizing your diet is like optimizing the engine in your car for long-term use. How much time and money do you want to spend on this as a project? However large your answer, you can easily find ways to spend those resources - it's a deep rabbit hole, with many side-passages, and one that lacks firm measures of success. Unless you make it your hobby and are happy tinkering for the sake of tinkering, I'd suggest that it's largely not worth it. You'd be better off doing something with your time that is more likely to prove constructive in the end. ... Look at it this way: the research community has established that no dietary practice is better for health and longevity in a range of species than calorie restriction - coupled with any of the standard, sane, recommended balanced diets of the sort that have been well known and well publicized for decades. ... The bottom line is that if you want to optimize your diet, just sensibly practice calorie restriction. End of story."
HOW FAR CAN BOOSTED AUTOPHAGY TAKE US?
Autophagy is a collection of processes by which components of cells are recycled, removing damage and reusing the materials. As researchers understand more about the controlling mechanisms, this makes it more likely that we will see autophagy-boosting therapies in the near future. Given that aging is only damage at its roots, where might this take us?
"Mitochondria in your cells damage themselves in the course of their vital, life-sustaining operations, and these damaged mitochondria contribute to aging. ... The importance of mitochondria is one of the reasons that autophagy is also important when it comes to the progression of aging. Autophagy is the name given to a collection of varied recycling machinery and processes that operate within cells, destroying damaged components - such as mitochondria. It shouldn't be a great leap to think that improving the recycling mechanisms might also improve the situation vis a vis malfunctioning mitochondria. This is probably the case, based on what researchers know of mitophagy, the processes of autophagy concerned with removing damaging mitochondria. Insofar as the bottom line of health and longevity goes, there is plenty of evidence to suggest that dialing up autophagy extends life, and a further array of evidence to suggest that known life-extending techniques such as calorie restriction depend heavily on autophagy as a principle mechanism of action. Based on what's coming out of the labs in recent years, I think the research community isn't too far away from conducting studies that will definitively show - or definitively disprove, which would be unexpected - benefits to longevity from improved mitoautophagy alone."
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!
A REMINDER THAT GENETIC CONTRIBUTIONS TO LONGEVITY ARE COMPLEX
Friday, August 26, 2011
Researchers are turning up a great many human genetic variants associated with natural differences in longevity - a complex, patchwork array of them, each contributing a small amount to the whole: "Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-α) genes may influence human life-expectancy. ... SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes ... Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males ... a significant two-loci interaction occurs in females between ADA 22G>A and TNF-α -238G>A ... both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-α genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity."
INDUCED PLURIPOTENCY, DRUG TESTING, AND PERSONALIZED MEDICINE
Friday, August 26, 2011
From the Technology Review: "I was observing an intimate demonstration of how stem-cell technologies may one day combine with personal genomics and personal medicine. I was the first journalist to undergo experiments designed to see if the four-year-old process that creates induced pluripotent stem (iPS) cells can yield insight into the functioning and fate of a healthy individual's heart cells. Similar tests could be run on lab-grown brain and liver cells, or eventually on any of the more than 200 cell types found in humans. ... This is the next step in personalized medicine: being able to test drugs and other factors on different cell types. ... the cardiomyocytes derived from iPS cells are a huge improvement over the cadaver cells sometimes used to test potential drug compounds. Unlike the cadaver cells, IPS-generated cells beat realistically and can be supplied in large quantities on demand. What's more, iPS-generated cells can have the same genetic makeup as the patients they came from, which is a huge advantage in tailoring drugs and treatments to individuals. ... Virtually everything about iPS cells is overhyped. But for the purpose of testing drug candidates, I think the possibilities are considerable, and we and lots of other people are pursuing this. There are lots of problems. Are iPS cells really normal? How do you get enough pure differentiated cells? But the potential is definitely there."
Thursday, August 25, 2011
Cryonics provider Alcor dedicates a section of their website to challenges and problems, and it is well worth reading: "When you buy a house, the seller is legally obliged to disclose any known defects. When you review a company's annual report, it tells you every problem that could affect the corporate share value. Since arrangements for cryopreservation may have a much greater impact on your life than home ownership or stock investments, we feel an ethical obligation to disclose problems that affect cryonics in general and Alcor specifically. We also believe that an organization which admits its problems is more likely to address them than an organization which pretends it has none. Thus full disclosure should encourage, rather than discourage, consumer confidence. ... As of 2011, Alcor is nearly 40 years old. Our Patient Care Trust Fund is endowed with more than 7 million dollars and is responsible for the long-term care of over 100 cryopatients. In almost every year since its inception Alcor has enjoyed positive membership growth. We are the largest cryonics organization in the world - yet in many respects we are still a startup company. We have fewer than a dozen employees in Scottsdale, Arizona and approximately 20 part-time independent contractors in various locations around the USA, mostly dedicated to emergency standby and rescue efforts. We serve fewer than 1,000 members and the protocols that aid our pursuit of the goal of reversible suspended animation continue to be developed. At the present time the technology required for the realization of our goal far exceeds current technical capabilities. Cryonics will not be comparable with mainstream medicine until our patients can be revived using contemporary technology, and we expect to wait for decades to see this vision fulfilled. Nevertheless, we have made important progress by introducing brain vitrification to improve patient tissue structure preservation. Alcor shares some of the characteristics of startup companies. The organization is understaffed in some important areas and lacks as much capitalization as would be desired to support maximum growth. Limited resources prevent the organization from hiring as many highly qualified and experienced personnel as desired, and sometimes we have to postpone enhancements to equipment and procedures." I think that this is a great document, and Alcor staff are to be congratulated for publishing it - absolutely the right thing to do.
PROGRESS IN REGENERATING TOOTH DECAY
Thursday, August 25, 2011
Good news from the dental research community: scientists "have developed a revolutionary new way to treat the first signs of tooth decay. Their solution is to arm dentists with a peptide-based fluid that is literally painted onto the tooth's surface. The peptide technology is based on knowledge of how the tooth forms in the first place and stimulates regeneration of the tooth defect. ... This may sound too good to be true, but we are essentially helping acid-damaged teeth to regenerate themselves. It is a totally natural non-surgical repair process and is entirely pain-free too. ... It contains a peptide known as P 11-4 that -- under certain conditions - will assemble together into fibres. In practice, this means that when applied to the tooth, the fluid seeps into the micro-pores caused by acid attack and then spontaneously forms a gel. This gel then provides a 'scaffold' or framework that attracts calcium and regenerates the tooth's mineral from within, providing a natural and pain-free repair. The technique was recently taken out of the laboratory and tested on a small group of adults whose dentist had spotted the initial signs of tooth decay. The results from this small trial have shown that P 11-4 can indeed reverse the damage and regenerate the tooth tissue. ... If these results can be repeated on a larger patient group, then I have no doubt whatsoever that in two to three years time this technique will be available for dentists to use in their daily practice."
CONSIDERING REPROGRAMMING CELLS IN THE BODY
Wednesday, August 24, 2011
So far research on cellular reprogramming has largely focused on manipulation of cells outside the body. Here a researcher suggests that the future of medicine will involve achieving much the same thing inside the body: "To date, somatic cell reprogramming has been achieved in vitro. It would be of great importance to explore whether the anti-aging agents, e.g. rapamycin, could function to enhance stem cell function, protect stem cell pluripotency and even promote reprogramming in vivo. It is also very interesting to verify whether some or all adult organs/tissues do possess some significant regenerative capacity due to the suspected in vivo reprogramming. Furthermore, it has been reported that agents which effectively function for a common human disease by enhancing self-renewal could lose efficacy in older individuals due to the age-associated decline of replication. Thus understanding and realization of in vivo cell reprogramming is not only a fundamental theoretical question but also a very promising strategy for anti-aging and regenerative medicine. Reprogramming of somatic cells has been enthusiastically hoped to become an arsenal to against aging as it would leads to personalized stem-cell-based rejuvenation therapies. What we learn from research of stem cell and reprogramming could help us to develop two potential anti-aging approaches in adult and older: i) to protect, ameliorate or reverse the age-associated loss function of stem cell in vivo and ii) to replace the lost stem cells by reprogrammed pluripotent cells."
STRESS, DNA DAMAGE, AND P53
Wednesday, August 24, 2011
Researchers here outline one possible mechanism for the known association between chronic stress and biomarkers of health: "While the human mind and body are built to respond to stress - the well-known "fight or flight" response, which lasts only a few minutes and raises heart rate and blood glucose levels - the response itself can cause significant damage if maintained over long periods of time. When stress becomes chronic, this natural response can lead to a number of disease-related symptoms, including peptic ulcers and cardiovascular disorders. To make matters worse, evidence indicates that chronic stress eventually leads to DNA damage, which in turn can result in various neuropsychiatric conditions, miscarriages, cancer, and even aging itself. ... The newly uncovered mechanism involves β-arrestin-1 proteins, β2-adrenoreceptors (β2ARs), and the catecholamines, the classic fight-or-flight hormones released during times of stress - adrenaline, noradrenaline, and dopamine. Arrestin proteins are involved in modifying the cell's response to neurotransmitters, hormones, and sensory signals; adrenoceptors respond to the catecholamines noradrenaline and adrenaline. Under stress, the hormone adrenaline stimulates β2ARs expressed throughout the body, including sex cells and embryos. Through a series of complex chemical reactions, the activated receptors recruit β-arrestin-1, creating a signaling pathway that leads to catecholamine-induced degradation of the tumor suppressor protein p53, sometimes described as "the guardian of the genome." The new findings also suggest that this degradation of p53 leads to chromosome rearrangement and a build-up of DNA damage both in normal and sex cells." p53 is very important in a range of core cellular processes - anything touching on it usually turns out to be influential.
METABOLIC SYNDOME AND KIDNEY DISEASE
Tuesday, August 23, 2011
Metabolic syndrome is, for the vast majority of us, an avoidable lifestyle condition. If you exercise and avoid gaining excess body fat then in all likelihood you won't suffer from the condition. Here's another reason to make that effort: "Metabolic syndrome comprises a group of medical disorders that increase people's risk of diabetes, heart disease, stroke, and premature death when they occur together. A patient is diagnosed with the syndrome when he or she exhibits three or more of the following characteristics: high blood pressure, high blood sugar, excess body fat in the waist/abdomen, low good cholesterol, and higher levels of fatty acids (the building blocks of fat). People with metabolic abnormalities are at increased risk of developing kidney disease ... [researchers] searched the medical literature and combined data from 11 studies examining the relationship between metabolic syndrome and kidney disease. Altogether, they included 30,416 individuals from various ethnic groups. ... People with metabolic syndrome have a 55% increased risk of developing kidney problems, especially lower kidney function, indicative of kidney disease. Individual components of metabolic syndrome are linked with the development of kidney disease. Kidney disease risk increases as the number of metabolic syndrome components increases. ... Preventing and managing metabolic syndrome - through eating a healthy diet, exercising, losing excess body weight, and lowering cholesterol, blood pressure, and blood sugar levels - may help prevent kidney disease."
THE MOUTH AS A SOURCE OF USEFUL STEM CELLS
Tuesday, August 23, 2011
Researchers are engaged in a body-wide hunt for stem cells that are easy to work with and easy to obtain - low cost sources will make a big difference to the ultimate cost of therapies: "As we age, our stem cells are less pliant and less able to transform into the stem cells that science needs to find breakthrough treatments for disease. An exception to this can be found in the stem cells of oral mucosa, the membrane that lines the inside of our mouths. ... A wound that might take weeks to heal and leave a life-long scar on the skin will be healed in a matter of days inside the mouth, regardless of the patient's age. ... Prof. Pitaru set out to determine if oral mucosa could be a source for young, fetal-like stem cells with this unique healing ability. Even when obtained from an older patient, he says, these stem cells still have properties of young or primitive stem cells - which have a high capacity to be transformed into different tissues. Prof. Pitaru and his fellow researchers have already succeeded in coaxing oral mucosa stem cells into becoming other significant cells, including bone, cartilage, muscle, and even neurons. ... Prof. Pitaru and his fellow researchers are currently in pre-clinical trials, implanting these stem cells into various tissues within small rodents. Their projects include researching the impact of the innovative cells as a treatment for chronic heart failure; neurodegenerative diseases; inflammatory autoimmune diseases such as Crohn's disease; and diabetes."
ARGUING FOR PROGRAMMED AGING
Monday, August 22, 2011
A proportion of the aging research community think aging to be at least partially a programmed phenomenon, rather than an accumulation of damage, and thus something to be primarily manipulated by changing the operation of our metabolism. Here is an argument for that viewpoint from researcher Michael Rose: "I should be clear that my present view is also not one generally held, at least not yet, even by most evolutionary biologists who work on aging. Like them, I spent more than thirty years thinking that William Hamilton's declining forces of natural selection, which he published in 1966, showed that evolution by natural selection would allow cumulative processes of physiological deterioration to proceed unchecked, provided they killed off their victims at sufficiently late ages. ... By 1994, I was thinking that perhaps evolutionary biologists had misconceived the problem of the evolution of aging. Perhaps it was NOT natural selection just letting go, but something that specifically tracked Hamilton's forces of natural selection. This led me to convince Larry Mueller to do some explicit simulations of evolution, simulations in which we looked at what happened at very late ages, long after Hamilton's forces of natural selection bottom out and stabilize. What the simulations generated were late-life plateaus in mortality ... we then checked how changes in Hamilton's forces would change the age at which mortality plateaus occur, based on explicit simulations. These simulations showed that changing the last age of reproduction in a biological population, the parameter that Hugh Hefner is working on as I write, would tune the age at which mortality rates would plateau."
TENSION IN GROWING MUSCLE TISSUE
Monday, August 22, 2011
Via ScienceDaily: researchers "have found a simple way to grow muscle tissue with real muscle structure in the laboratory. They found that the muscle cells automatically align themselves if they are subjected to tension in one direction - this is essential for the ability of the muscle cells to exert a force. The endothelial (blood vessel) cells in the culture also automatically grouped themselves to form new blood vessels. This finding is a step forward towards the engineering of thicker muscle tissue. ... Another important aspect of the finding is that it was not necessary to add any biochemical growth factors to initiate the process. These substances are normally required for processes of this kind, but their action is difficult to control. ... Measurements by the researchers showed that the muscle cells produced the required growth factor themselves, as a result of the tension to which they were subjected. ... The aim of the research is ultimately to allow the treatment of people who have lost muscle tissue, for example through accidents or surgery to remove tumors."