Allow me to point you to the results of a long-running study on metabolic rate and mortality:

Higher metabolic rates increase free radical formation, which may accelerate aging and lead to early mortality. ... Our objective was to determine whether higher metabolic rates measured by two different methods predict early natural mortality in humans. ... Twenty-four-hour energy expenditure (24EE) was measured in 508 individuals, resting metabolic rate (RMR) was measured in 384 individuals.

The study ran with hundreds of participants over more than twenty years and concluded that there is a good correlation between these measures of metabolic rate and risk of death:

For each 100-kcal/24 h increase in EE, the risk of natural mortality increased by 1.29 in the 24EE group and by 1.25 in the RMR group, after adjustment for age, sex, and body weight in proportional hazard analyses.

The higher your resting metabolic rate, the greater your expected chance of death by aging or disease sometime soon - a cheerful prospect. My first thought was that these measurements should reflect levels of physical fitness achieved through exercise, which we know has a strong effect on mortality, but apparently not:

Studies published in 1992 and 1997 indicate that the level of aerobic fitness of an individual does not have any correlation with the level of resting metabolism. Both studies find that aerobic fitness levels do not improve the predictive power of fat free mass for resting metabolic rate.

There's a lesson there concerning the practice of quickly leaping to what might seem to be sensible conclusions. My slower second thought involved calorie intake: even mild levels of calorie restriction have measurable impacts on health in humans and on longevity in lower animals. Possibly also on longevity in humans, though that study will likely never be undertaken - if started tomorrow, by the time it was even half-way complete we'd be well into the era of rejuvenation biotechnology, making the whole exercise rather pointless.

In any case, the practice of calorie restriction does lower resting metabolic rate, and does so across a range of species: stick insects, rhesus monkeys, and humans, to pick a few. So it seems reasonable to theorize that differences in mortality seen in the study quoted above are reflections of the natural variance of calorie intake amongst the participants, and the biochemical - and existential - consequences of lower versus higher calorie diets.

Here is an example of a research commentary that misses the forest for the trees: "Vegetarians experience a 36 percent lower prevalence of metabolic syndrome than non-vegetarians, suggests new research ... Because metabolic syndrome can be a precursor to heart disease, diabetes, and stroke, the findings indicate vegetarians may be at lower risk of developing these conditions. Metabolic syndrome is defined as exhibiting at least three out of five total risk factors: high blood pressure, elevated HDL cholesterol, high glucose levels, elevated triglycerides, and an unhealthy waist circumference. ... while 25 percent of vegetarians had metabolic syndrome, the number significantly rises to 37 percent for semi-vegetarians and 39 percent for non-vegetarians. The results hold up when adjusted for factors such as age, gender, race, physical activity, calories consumed, smoking, and alcohol intake. ... On average, the vegetarians and semi-vegetarians were three years older than non-vegetarians. Despite their slightly older age, vegetarians had lower triglycerides, glucose levels, blood pressure, waist circumference, and body mass index (BMI). Semi-vegetarians also had a significantly lower BMI and waist circumference compared to those who ate meat more regularly." Given the broader context of what is known about the effects of body fat on long-term health, the plausible mechanism here looks to be related to the amount of visceral fat rather than anything to do with diet per se.

Link: http://www.eurekalert.org/pub_releases/2011-04/llua-vmb041311.php

Small scale efforts by a widespread people outside the academic and industry communities, and open and largely free access to plans and data are the future of biotechnology. It is a data-driven field, and will ultimately look just like the open source software community does today: "Following in the footsteps of revolutionaries like Steve Jobs and Steve Wozniak, who built the first Apple computer in Jobs's garage, and Sergey Brin and Larry Page, who invented Google in a friend's garage, biohackers are attempting bold feats of genetic engineering, drug development, and biotech research in makeshift home laboratories. ... For a few hundred dollars, anyone can send some spit to a sequencing company and receive a complete DNA scan, and then use free software to analyze the results. Custom-made DNA can be mail-ordered off websites, and affordable biotech gear is available on Craigslist and eBay. ... biohackers, like the open-source programmers and software hackers who came before, are united by a profound idealism. They believe in the power of individuals as opposed to corporate interests, in the wisdom of crowds as opposed to the single-mindedness of experts, and in the incentive to do good for the world as opposed to the need to turn a profit. Suspicious of scientific elitism and inspired by the success of open-source computing, the bio DIYers believe that individuals have a fundamental right to biological information, that spreading the tools of biotech to the masses will accelerate the pace of progress, and that the fruits of the biosciences should be delivered into the hands of the people who need them the most."

Link: http://www.technologyreview.com/biomedicine/37444/

One approach to developing targeted therapies is to co-opt existing biological structures, such as cells and bacteria: "Scientists have developed bacteria that serve as mobile pharmaceutical factories, both producing disease-fighting substances and delivering the potentially life-saving cargo to diseased areas of the body. ... [Researchers] chose the term 'bacterial dirigibles' because the modified bacteria actually have the fat-cigar look of blimps and zeppelins, those famous airships of yesteryear. ... We're building a platform that could allow bacterial dirigibles to be the next-generation disease fighters. ... traditional genetic engineering reprograms bacteria so that they produce antibiotics, insulin, and other medicines and materials. The bacteria grow in nutrient solutions in enormous stainless steel vats in factories. They release antibiotics or insulin into vats, and technicians harvest the medicine for processing and eventual use in people. The bacterial dirigible approach takes bioengineering a step further. Scientists genetically modify bacteria to produce a medicine or another disease-fighting substance. Then, however, they give the bacteria a biochemical delivery address, which is the locale of the disease. Swallowed or injected into the body, the bacteria travel to the diseased tissue and start producing substances to fight the disease. ... We have created a genetic circuit that endows E. coli with targeting, sensing and switching capabilities. ... The 'targeting' molecule is attached to the outer surface of the bacteria. It gives the bacteria an ability to 'hone in' on specific cells and attach to them - in this instance, the intestinal cells where other strains of E. coli cause food poisoning symptoms. Inside the bacteria is a gene segment that acts as 'nanofactory.' It uses the bacteria's natural cellular machinery to make drugs, such as those that can fight bacterial infections, viruses, and cancer. The nanofactory also could produce signaling molecules that enable the dirigible to communicate with natural bacteria at the site of an infection. Some bacteria engage in a biochemical chit-chat, termed 'quorum sensing,' in which they coordinate the activities needed to establish an infection. Bacteria dirigibles could produce their own signaling molecules that disrupt quorum sensing."

Link: http://www.sciencedaily.com/releases/2011/03/110329134120.htm

The many types of advanced glycation endproducts, or AGEs, build up with age. These are forms of sugary gunk that glue together important components in your cellular machinery, and enough of that going on would ultimately become a fatal problem. AGE levels are probably (for most people) more of a contributory cause than principle cause of age-related degeneration, however. The other things kill you first - but it's all a matter of accumulation, and every form of unrepaired biological damage plays its part in hastening the end.

It is likely that the way in which AGEs cause issues has just as much to do with making cells act in counterproductive ways as it does with outright destruction of essential mechanisms. An important focus of research is RAGE, the cellular receptor for AGEs, which is involved in the inflammatory response. As I'm sure you know by now, chronic inflammation is very bad for you over the long term, and goes a long way towards degrading health and remaining longevity. If your body is flooded with AGEs, then one consequence is inflammation - and that in turn will cause harm over time in many different ways.

The picture of AGEs and aging is already complicated by diet - some AGE levels are very variable, and depend on what you happen to be eating - and metabolic conditions such as diabetes wherein the overall behavior of human metabolism is quite different from that of an aged but otherwise normal person. Much of the modern populace eats far too much, and far too much sugar as well, which leads to these sorts of conditions of overnutrition.

Today I noticed an open access paper that adds another layer of complexity to the picture of AGEs and aging. Bacteria produce AGEs, and RAGE and its connection to the inflammatory response may be a component part of the immune system - a mechanism that evolved long before we humans had ready access to the damaging levels and types of food we presently consume.

Advanced Glycated End Products (AGEs) are formed by non-enzymatic protein glycation and are implicated in several physiological aspects including cell aging and diseases. Recent data indicate that bacteria - although short lived - produce, metabolize and accumulate AGEs. Here we show that Escherichia coli cells secrete AGEs by the energy-dependent efflux pump systems. Moreover, we show that in the presence of these AGEs there is an upshift of pro-inflammatory cytokines by mammalian cells.

Thus, we propose that secretion of AGEs by bacteria is a novel avenue of bacterial-induced inflammation which is potentially important in the pathophysiology of bacterial infections. Moreover, the sensing of AGEs by the host cells may constitute a warning system for the presence of bacteria.

So in short, it would seem plausible that the reaction to accumulating AGEs is yet another way in which both modern overnutrition and the established course of aging act separately but combine to sabotage the evolved workings of the immune system. We already know that the immune system is formed to be very efficient in youth but structurally fails over time, so one more mechanism that follows this pattern shouldn't be too surprising.

The only good news here is that safely getting rid of AGEs should be one of the least challenging aspects of aging for the present pharmaceutical research and development community to tackle over the next few decades - as and when they get around to deciding that they should be working on that. Producing drugs, bioremediation therapies, or immune therapies to break down specific forms of unwanted chemical will soon enough be the core competency of the pharmaceutical industry.

Type 2 diabetes is a lifestyle disease, avoidable for vast majority of people. If you overeat, become fat, and live a sedentary life then the odds are good you'll develop the condition, or at least its precursor, metabolic syndrome. The cost of this neglect of health basics is measurable: "Middle-aged adults with diabetes are much more likely to develop age-related conditions than their counterparts who don't have diabetes, according to a new study ... Adults between 51 and 70 with diabetes developed age-related ailments like cognitive impairment, incontinence, falls, dizziness, vision impairment and pain at a faster rate than those without diabetes, the study found. ... Our findings suggest that middle age adults with diabetes start to accumulate these age-related problems. Because diabetes affects multiple organ systems, it has the potential to contribute significantly to the development of a number of issues that we associate with aging ... For adults aged 51-60 with diabetes, the odds of developing new geriatric conditions were nearly double those of their counterparts who didn't have diabetes, the researchers found. By the time people with and without diabetes reach 80, the overall effects of aging and impact of other diseases start to reduce the disparities between the two groups. ... The findings suggest that adults with diabetes should be monitored for the development of these conditions beginning at a younger age than we previously thought." Though of course your odds of making it to 80 to be compared to your healthier cohorts are not as good if you're diabetic. So don't get fat, don't stay fat, and exercise sounds like good advice.

Link: http://www.eurekalert.org/pub_releases/2011-03/uomh-acd033111.php

A little stress improves our biochemistry: "Recent evidence suggests that calorie restriction and specifically reduced glucose metabolism induces mitochondrial metabolism to extend life span in various model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and possibly mice. In conflict with Harman's free radical theory of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately cause a long-term reduction of oxidative stress. This type of retrograde response has been named mitochondrial hormesis or mitohormesis, and may in addition be applicable to the health-promoting effects of physical exercise in humans and, hypothetically, impaired insulin/IGF-1-signaling in model organisms. Consistently, abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. In summary, the findings discussed in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20350594

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Regular intake of table sugar and fruit sugars have been linked to increased blood pressure, study says.

Based on a new study from the National Health & Nutrition Examination Survey, regular intake of table sugar or fruit sugars can increase a person’s risk of doubling his risk of dramatically increasing his systolic blood pressure above the 160 mark. Normal systolic blood pressure should be no more than 120.

Growing body of evidence

According to one of the researchers, Michael Chonchol MD from the University of Colorado in Denver, systolic blood pressure really is the determining factors when it comes to determining health outcomes.

Though more research is needed for a more conclusive statement regarding the connection between sugar intake and high blood pressure, the American Heart Association has already released a formal statement that said that an emerging body of studies is pointing at the potential lead role of sugar in high blood pressure.

As such, people should limit their intake of food with added fruit sugars or table sugar to reduce their risk of developing hypertension.

Lowering blood pressure naturally

You don’t have to be dependent all your life on heart medications. If you want to lower your blood pressure naturally today, you can do that. Follow our steps on lowering your blood pressure naturally:

1. Eat foods that are high in soluble fiber, fruits, anti-oxidant rich vegetables, low-fat dairy products (such as yogurt and skim milk) and low in saturated fat.

Limit your intake of red meats as well and limit your intake of processed foods and frozen deserts to reduce your sugar intake. It is also recommended that people reduce their intake of soda and other sugary drinks to limit your intake of corn syrup and similar sweeteners.

2. Salt intake should be no more than 2,400 milligrams daily. Check the labels of your food products at home to check just how much sodium is going into your body whenever you eat dinner or snack on a bag of chips or cookies.

Some sports drinks also have sodium added (as ‘electrolytes’). This form of sodium can also raise your blood pressure. If you think your regular diet is sodium-rich, you have to balance your body’s chemistry by adding more potassium to your diet.

Potassium-rich foods include bananas, avocado, etc. When you are doing your grocery shopping, choose low-salt alternatives to regular processed foods.

When cooking food at home, always add salt at the end of the cooking process so you would need to add only a very small amount (if it all). The healthier alternative would of course to replace salt with spices and non-salt based flavorings.

3. Exercise at least thirty minutes every day (for a total of 150 minutes of conventional/traditional exercise every week). Weight loss equivalent to 10 pounds can already produce dramatic reductions in blood pressure.

Three types of exercise are recommended for weight loss and blood pressure reduction efforts: stretching, cardiovascular exercises (also known as aerobic exercise) and strengthening exercises. Remember, there are three phases for every exercise: warm-up, conditioning and cool-down.

4. Alcohol consumption should also be reduced to two drinks everyday or less (or none!). Women should have no more than one drink per day to control blood pressure. One serving is equivalent to twelve ounces of regular beer, five ounces of wine (any type of wine) or 1.5 ounces of 80-proof liquors.

5. You have to lower your cholesterol level too, if you want to permanently reduce your blood pressure. You can do this by eating more fiber, exercising more and avoiding foods that have been loaded with saturated fats. You can also stock up on potent antioxidants known as polyphenols by drinking green tea. Nuts are also rich in antioxidants and can naturally lower your bad cholesterol level.

Sources:
nytimes.com
webmd.com
webmd.com
webmd.com
webmd.com
webmd.com

Discuss this post in Frank Mangano’s forum!

Cutting back on soda directly improves a person's blood pressure. Over time, the benefits of this practice will also continue to increase.

Today, the average American consumes 28 fl. oz. of sodas and other sugary drinks everyday – an alarming fact considering that new research has discovered the vital link between these sugary drinks and blood pressure.

According to research done by Dr. Liwei Chen from the Louisiana State University, cutting back on your consumption of sugary beverages has a direct impact on your blood pressure.

The 3-point difference

In the randomized study involving 810 adult Americans (aged twenty five to seventy nine), Dr. Chen observed that halving the usual consumption of sodas produced a 3-point reduction in blood pressure. What does this mean?  Well, a 3-point reduction in blood pressure also reduced the incidence of a heart attack by a hefty eight percent.

Mortality associated with cardiovascular incidents was also reduced by five percent.  During the study, the 810 respondents were given beverages that had been sweetened with corn syrup – the most common sweetener used in the beverage and food industries today.

According to Dr. Chen, if a person were to gradually reduce his or her soda consumption over a long period of time, then the benefits to a person’s heart is also for the long term.  And that’s not all, a person who reduces his consumption of soda also protects himself more efficiently from stroke – one the greatest silent killers in medical history.

Soda & blood pressure?

But many people are still wondering: what does soda consumption really have to do with blood pressure?  There are two theories supporting the move to reduce the intake of sodas and sugary drinks: the sodium theory and the uric acid theory.

You see, many commercial beverages are loaded with sodium, the same stuff that we use to season food. Sodium has the capacity to directly raise a person’s blood pressure.

Also, the sweetener used for these beverages also contributes to the increase of a person’s uric acid, which is also directly associated with high blood pressure.  In addition to high blood pressure, increased uric acid can also contribute to a higher probability of developing gouty arthritis – a very painful form of arthritis.

Tips for lowering your blood pressure

1. Avoid eating too much fast food and processed food – foodstuffs developed by most food sectors are loaded with at least 40% more sodium than what is considered safe by the US FDA.

2.If you can, use spice substitutes when cooking. Avoid using too much salt when cooking.  Your blood pressure can progressively increase through time.

3. You don’t have to spend a cent to exercise – start getting fit today.  Five minutes of brisk walking, done everyday, can do wonders for your blood pressure.

4. Cut down on smoking – cigarettes and cigars have been shown to raise blood pressure.  If you stop smoking for just 1 to 2 hours, your blood pressure begins to go down.

References:
webmd.com
disease/article32650.html
rd.com
rd.com

Researchers are turning up new longevity genes at a fair rate these days, and this latest discovery is illustrative of the methods used - start with what you know, and compare and contrast: "A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20519778

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

An interesting article: "In what turned out to be his final official engagement as CEO of Sirtris Pharmaceuticals, Christoph Westphal offered some key lessons in how to build a successful biotech company ... It's pretty amazing ... in the last 20 years, we've gone from zero understanding of the genes that play a role in aging to a pretty clear understanding that IGF1 plays a role, MTOR, the Sirtuins play a role, there's 10-15 genes play a role. Many of those are going to be druggable targets. Will Sirtris be successful? I don't know. It's still going to be very risky. But I'll be shocked if there are not drugs in the next 10-15 years that target genes that control aging. ... Westphal did not shirk from addressing the ongoing controversy surrounding the physiological activity of some Sirtris compounds. ... There's a debate in the academic world. We don't know the specific molecular mechanism of why you need a specific substrate on the in vitro screen to find Sirt1 activators. ... It's a numbers game and it's gotten harder with the FDA ... People are spending less on pharma R&D and more on consumer health care and trying to diversify into developing countries and away from Europe and the United States. Fewer drugs are getting approved, revenues are going down, margins are going to go down."

View the Article Under Discussion: http://www.bio-itworld.com/news/04/26/10/Christoph-Westphal-on-aging-pharmageddon.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Insulin-like growth factor 1 (IGF-1) is one of the more studied areas of known overlap between metabolism and longevity, but given the innate complexity of biology in mammals there is always some debate over the degree to which IGF-1-related mechanisms are actually determinants of life span, or even correlated with life span. Here is a study in sheep, not the usual species in investigations of the biochemistry of aging: "Longevity in livestock is a valuable trait. When productive animals live longer fewer replacement animals need to be raised. However, selection for longevity is not commonly the focus of breeding programs as direct selection for long-lived breeding stock is virtually impossible until late in the animal's reproductive life. Additionally the underlying genetic factors or genes associated with longevity are either not known, or not well understood. In humans, there is evidence that insulin-like growth factor 1 receptor (IGF1R) is involved in longevity. Polymorphism in the IGF1R gene (IGF1R) has been associated with longevity in a number of species. Recently, 3 alleles of ovine IGF1R were identified, but no analysis of the effect of IGF1R variation on sheep longevity has been reported. In this study, associations between ovine IGF1R variation, longevity and fertility were investigated [in] 1716 New Zealand sheep belonging to 6 breeds and 36 flocks. ... Ovine IGF1R C was associated with age when adjusting for flock [and] a weak negative [correlation] between fertility and longevity traits was observed."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22585783

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Much of the mainstream aging research community has little interest in building therapies for aging, being focused on investigation only - though, fortunately, this situation is changing rapidly these days. The past stigma associated with public discussion of treating and ultimately preventing aging has largely evaporated within the scientific world.

Among those researchers who are interested in therapies for aging, most are focused on the slow boat of metabolic alteration: work that will have comparatively little pay-off even if successful, but which fits more readily into established research programs and the prejudices of research funding institutions.

The principal downside of metabolic alteration strategies, from my point of view, is that even if successful they cannot produce any significant longevity benefit in a person already old. All it can do is slow down aging by a modest amount - which isn't terribly useful those already aged and damaged. Even under the most optimistic estimates it will take another twenty years and many billions of dollars to see the evolution of a robust market in commercially available human metabolic enhancements to slow aging. It is a challenging field of research, and progress to date has been slow even in this era of rapid advances in biotechnology.

There is another disadvantage, which is illustrated by the different degrees to which life span is enhanced by similar strategies applied in mice versus humans. It is taken for granted in the literature, and thus probably not emphasized to the degree it should be, that an extension of life by 50% in mice based on some genetic or metabolic alteration - such as calorie restriction or growth hormone knockout - is probably not going to map to a similar extension of life in humans. If humans could achieve that sort of life extension through simply eating well and eating less or being growth hormone mutants, we'd have known about it by now. Consider Laron dwarfism, for example, or the generation after generation of practitioners of various degrees of calorie restriction that exist in many cultures.

With an eye to this second disadvantage, I'll point out an open access paper that considers the evolution of aging from the point of view of the maintenance gap. This is the gap between the cost of maintenance required to keep an organism from aging and the resources actually devoted to maintenance - both of which are subject to evolutionary selection pressures, which operate to maximize success in genetic propagation rather than the comfort or longevity of individual members of a species. The paper was published last year, but showed up in a recent issue of Biogerontology.

The maintenance gap: a new theoretical perspective on the evolution of aging

One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, 'maintenance requirement' has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation.

Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms.

This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this.

The point to take away from this argument is that we should expect to find a broad variation between species in their response to similar forms of metabolic and genetic alteration aimed at extending life span. So far, that is what is seen, with we humans having the short end of the stick - though obviously there is an ocean of data yet to be obtained on this topic. On the whole, though, it seems like one more slowly building argument for the research community to focus on repair-based strategies for treating aging: build biotechnologies that are explicitly designed to repair forms of biological damage that existing repair systems either cannot handle or handle too slowly. SENS is the most obvious example, though I expect other, competing repair-focused visions to emerge in the years ahead as the SENS Foundation obtains further scientific support and promising research results.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Scientists proceed in their work by discovering a correlation and then picking apart the underlying mechanisms to find out why the correlation exists. In the field of aging research a great many as yet unexplained correlations exist, any one of which may point the way to important new knowledge. Take this for example: "Biological rhythms that oscillate with periods close to 24 h (circadian cycles) are pervasive features of mammalian physiology, facilitating entrainment to the 24 h cycle generated by the rotation of the Earth. In the absence of environmental time cues, circadian rhythms default to their endogenous period called tau, or the free-running period. This sustained circadian rhythmicity in constant conditions has been reported across the animal kingdom, a ubiquity that could imply that innate rhythmicity confers an adaptive advantage. In this study, we found that the deviation of tau from 24 h was inversely related to the lifespan in laboratory mouse strains, and in other rodent and primate species. These findings support the hypothesis that misalignment of endogenous rhythms and 24 h environmental cycles may be associated with a physiological cost that has an effect on longevity."

View the Article Under Discussion: http://pmid.us/20392719

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

An open access review paper: "Several studies suggest that an increase in adult neurogenesis has beneficial effects on emotional behavior and cognitive performance including learning and memory. The observation that aging has a negative effect on the proliferation of neural stem cells has prompted several laboratories to investigate new systems to artificially increase neurogenesis in senescent animals as a means to compensate for age-related cognitive decline. ... recent evidences indicate that the relative abundance of stem cells in certain organs does not necessarily correlate with their impact on organ function. Specifically, the mammalian brain is perhaps the organ with the lowest regenerative potential but the one in which the signs of aging are more manifested. Using the words of the renaissance writer Michel de Montaigne, 'age imprints more wrinkles on the mind than it does on the face' indicating that age-related cognitive decline has the highest impact on the quality of life. To which extent this decline is dependent on neural stem and progenitor cells (together referred to as NSCs) is hard to tell but growing evidences indicate that, despite their negligible numbers, the few resident NSCs that are located in specific brain regions, most notably the subgranular zone of the hippocampus, seem to play a major role in cognitive functions such as learning, memory, and emotional behavior by generating, through intermediate progenitors, neurons that are constantly added to the brain circuitry throughout life. ... the available data strongly suggests that aging almost exclusively acts at the level of NSC proliferation. Yet, the many contradicting results and uncertainties on identifying the exact causes of this 'decreased proliferation' [need] to be fully acknowledged in order to give a rigorous and meaningful direction to this relatively new field. ... The fact that NSCs can efficiently respond to physiological and pathological stimuli to increase neurogenesis indicates that stimulation of endogenous NSCs offers a promising alternative to transplantation approaches that until now were intensely investigated."

Link: http://impactaging.com/papers/v4/n3/full/100446.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

An introduction to calorie restriction at h+ Magazine: "In the early twentieth century nutrition researchers found that rats maintained on reduced caloric intake showed lower spontaneous tumors compared to rats fed ad libitum (allowed to eat as much as they chose). Although this work did not address caloric restriction (CR) and aging, it suggested that CR might slow the onset of age-associated disease in rodents. ... Numerous follow-up studies demonstrated that a micronutrient adequate CR diet significantly increased the lifespan of many species, largely crossing species boundaries. ... While CR increases the lifespans of most species examined, it also suppresses many of the diseases associated with human aging, thus increasing the 'health-span.' Over short periods, CR lowers blood pressure, heart rate, and glucose levels, and improves memory in older individuals and measures of cognitive performance in animals. Over longer periods CR significantly reduces the risk for many different types of cancer, age-related brain atrophy, heart disease (and atherosclerosis related diseases), autoimmune disease, and adult onset diabetes. CR appears to lessen the risk for, and attenuates or even reverses the symptoms of Alzheimer's and possibly Parkinson's diseases; two major age-related neurodegenerative diseases that cause enormous human suffering. ... Interestingly, CR appears to promote the progression of Amyotrophic Lateral Sclerosis (Lou Gehrig's disease), indicating it does not protect from all human diseases. Aging causes extensive, often organ-specific changes in gene expression patterns. Analysis [has] shown that aging, calorically restricted mice show gene expression patterns resembling those of young animals, compared to ad libitum-fed mice of the same age. CR also lowers cellular oxidative damage by reducing mitochondrial oxygen free radical production, lessens age-related telomere shortening, lowers inflammation, increases DNA damage repair efficiency and lowers damage to DNA and RNA (thus promoting genomic stability), lowers insulin levels while promoting insulin sensitivity, reduces the number of senescent (non-dividing) cells that accumulate with aging, attenuates age-related cellular protein cross-linking, and increases the removal of damaged cellular proteins - a process called 'autophagy' which declines with age and plays a role in resistance to infection, cancer, heart disease, and neurodegeneration. "

Link: http://hplusmagazine.com/2012/04/04/caloric-restriction-and-longevity/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

From Depressed Metabolism: "It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death ... Cryonicists have named their favorite conception of death 'information-theoretic death.' In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person's memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death."

Link: http://www.depressedmetabolism.com/2011/05/16/neural-cryobiology-and-the-legal-recognition-of-cryonics/

A Science News article here looks at the most well known and best funded research into slowing aging. It is all a matter of great expense to achieve very modest goals in slowing aging, and that almost as a side-effect of the main aim, which is to catalog and understand the biochemistry of metabolism.

A drug that postpones aging could also have profound health benefits, since most common diseases (such as cancer, heart disease and dementia) accompany old age. "That's what's driving us," says Donald Ingram, head of the nutritional neuroscience and aging laboratory at Pennington Biomedical Research Center in Baton Rouge, La. "We would like to see some kind of a product that would promote healthy aging."

So far, scientists have singled out a handful of synthetic and natural compounds that appear to trigger the same biochemical mechanisms that kick in when cells are partially starved of nutrients, part of a coping mechanism that protects against stress.

This sort of research accounts for the vast majority of funding in longevity science, and if that remains true then we'll live just a little bit longer than our parents. Perhaps as much as ten years longer if the metabolic engineers pull an unexpected amazing advance from their hats within the next decade.

From where I stand, that outcome would be a disaster - a missed opportunity with a cost of more than 50 million lives lost to aging and disease each and every year. If we reach 2040, after five decades of a scientific revolution in biotechnology, computing, and the ability to manipulate the fundamental components of life, and have not yet developed true rejuvenation biotechnology, capable of repairing the biochemical damage that causes aging ... well, we failed, and then some.

Presently, that grand failure through a focus on trivial success is exactly where the scientific and medical development community is headed. Their timelines are for drugs and metabolic manipulations that give a small number of additional years of life to emerge by 2030 - decades of tinkering, decades of trials, and we're all old by the time that any modestly useful result emerges into general use. Yet the research community, the public, and the press are all absolutely focused on slowing aging, where they think about aging at all. Far too few people realize just how damaging to our prospects this state of affairs will be in the long run.

This is why efforts like the SENS Foundation are so important: we need to see more groups building a platform, a body of work, and successfully making inroads into persuading the scientific community to work on repair of aging rather than just slowing it down. It won't take any longer to achieve meaningful success in repair-based research, given where things stand today, but the resulting difference to our lives and our health couldn't be greater.

Via EurekAlert!: researchers have "explained how rapamycin, a drug that extends mouse lifespan, also causes insulin resistance. The researchers showed in an animal model that they could, in principle, separate the effects, which depend on inhibiting two protein complexes, mTORC1 and mTORC2, respectively. The study suggests that molecules that specifically inhibit mTORC1 may combat age-related diseases without the insulin-resistance side effect. ... The mTOR complexes, for mammalian (or mechanistic) target of rapamycin, are proteins that regulate cell growth, movement, and survival, as well as protein synthesis and transcription. Specifically, there are two mTOR complexes and one mTOR protein. The mTOR protein is the core of both complexes (mTORC1 and mTORC2), which behave differently based on their associated proteins. One or both of the mTOR complexes can be inappropriately activated in certain cancers, and dual-specific inhibitors are being developed as chemotherapeutic agents. Several theories have been put forward by researchers to explain the observations that patients receiving rapamycin are more prone to developing glucose intolerance, which can lead to diabetes. Chronic treatment with rapamycin impairs glucose metabolism and the correct functioning of insulin in mice, despite extending lifespan. The research team demonstrated that rapamycin disrupts mTORC2 in the mice, and that mTORC2 is required for the insulin-mediated suppression of glucose metabolism in the liver. On the other hand, they also demonstrated that decreasing mTORC1 signaling was sufficient to extend lifespan independently from changes in glucose metabolism. They used a mouse strain in which mTORC1 activity was decreased and saw that lifespan was extended by 14 percent, yet the animals had normal glucose metabolism and insulin sensitivity."

Link: http://www.eurekalert.org/pub_releases/2012-03/uops-dol032612.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

From Alcor News: "The Alcor Video Library has recently added new material. It now includes a short Video Tour of Alcor Facility and five complete presentations from the 2006 Alcor Conference. The video quality has also been significantly upgraded. ... The Limitless Future (28-minutes). Alcor documentary video (2005). Discover how leading-edge science at the Alcor Life Extension Foundation is getting closer to making the dream of a vastly extended lifespan come true and how our notion of "death" is shifting. Includes interviews with world-renowned scientists including Dr. Aubrey de Grey, [explaining] how life can be cryopreserved on the verge of death and then revitalized, giving us a second chance at a long and productive life, and Dr. Ralph Merkle, Distinguished Professor of Computing at Georgia Tech, exploring how molecular-sized machines will be able to repair damage to your body from aging or the devastating effects of cancer and other illnesses, including frostbite." You might also take a look at some of the other videos linked in the post, such as a presentation on the economics of longevity: "In this talk, Dr. Friedman shares his insights into the many potential consequences of an extended lifespan. He asks provocative questions about the future of the family unit, a typical career path, and the economic outlook for society as a whole."

Link: http://www.alcor.org/blog/?p=2040