One of the pleasant aspects of the repair approach to intervention in aging, such as that proposed in the Strategies for Engineered Negligible Senescence (SENS), is that all distinct forms of repair therapy can reasonably be expected to complement one another. Undergo a procedure to fix mitochondrial damage or break down an AGE such as glucospane, for example, and you are better off. Undergo both therapies and you will gain a commensurately greater benefit.

Unfortunately, this expectation of complementary therapies is very much not the case when it comes to attempts to slow down aging by genetic, epigenetic, or other metabolic manipulation. Metabolism is enormously complex, and even the well-studied phenomenon of calorie restriction isn't yet fully understood in terms of how the machinery of genes, proteins, and controlling signals all ties together to increase life span and improve health. Varied methods of extending life by slowing aging often turn out to operate on different portions of the same mechanism, or harmful when used together even though they are beneficial on their own.

One thing often tried by research groups that discover a novel way of slowing aging in laboratory animals is to try out the new method in calorie restricted animals: will the effects on life span complement one another and thus lead to a greater extension of life than is the case for either method on its own? Few presently known genetic alterations or other methods of slowing aging produce more than a 30% life extension in mice, and the standing record is 60-70% for growth hormone deficient mice - so at this point in time, it seems unlikely that any new life span record will be set through slowing aging without employing some complementary combination of techniques.

That this hasn't yet happened suggests that we shouldn't hold out much hope for the next five to seven years - there has, after all, been a lot of experimentation in mice over the past decade, and especially since the record set using growth hormone deficient mice. Unfortunately purely negative results don't tend to be published as often as positive results, so it's not a straightforward matter to find out which combinations of the various known methods to slow aging in mice have been tried only to fail.

Nonetheless, one example showed up recently in work on extending mouse longevity with AC5 knockout (AC5 KO) and calorie restriction, and here is a commentary on that research that clearly makes the point:

Models of longevity (Calorie Restriction and AC5 KO): Result of three bad hypotheses

Third Incorrect Hypothesis: The most widely studied model of longevity is calorie restriction (CR). Our hypothesis was that combining these two models would produce a super longevity model. Accordingly, we placed AC5 KO mice on CR. Within a month we found that all the AC5 KO mice on CR had died. Accordingly, we had to change our hypothesis to include that the AC5 KO and CR models share similar protective and metabolic mechanisms, which could mediate longevity and health, but when superimposed are actually lethal.

This might be taken as a cautionary note on metabolic manipulation as a path to slowing aging: there are pitfalls, it is enormously complicated, and there isn't much of a roadmap in comparison to the path to repair-based strategies of the sort outlined in the SENS vision.

Source:
http://www.fightaging.org/archives/2012/11/not-all-longevity-manipulations-play-nice-together.php

One of the many ways in which FDA regulation corrupts research and development in medicine is the creation of a strong financial incentive to reuse existing drugs. It's much less expensive to obtain regulatory approval for a new marginal use of a drug already approved for other uses than it is to obtain regulatory approval for a completely new drug or other medical technology that might be far better. This discourages real progress in favor of something that only looks a little like progress: many of the existing stable of drugs are decades old, yet resources that might otherwise go to breaking new ground are instead poured into shoving these old square pegs into as many round holes as possible.

Given this it should be no great surprise to see that as work on the biology of calorie restriction has progressed, an increasing amount of time and money has been devoted to attempts to reuse existing drugs as calorie restriction mimetics - i.e. to find approved drugs that produce at least some of the same changes in metabolism, and with as few side-effects as possible. One of these drugs is metformin, but as I noted in a post earlier this year, it really isn't much to write home about, given that results from a range of studies are all over the map. It may or may not be useful or beneficial, and certainly doesn't show the clear benefits to health and life expectancy produced by calorie restriction itself:

Studies of the potential antiaging effects of antidiabetic biguanides, such as metformin, are still experimental for obvious reasons and their results are currently ambiguous.

Today I thought I'd direct your attention to a recent paper that shows metformin failing to do much for fly life spans:

Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila

The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1.

We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster. We show here that while feeding metformin to adult Drosophila resulted in a robust activation of AMPK and reduced lipid stores, it did not increase lifespan in either male or female flies. In fact, we found that when administered at high concentrations, metformin is toxic to flies. Furthermore, no decreases in female fecundity were observed except at the most toxic dose. Analysis of intestinal physiology after metformin treatment suggests that these deleterious effects may result from disruptions to intestinal fluid homeostasis.

Thus, metformin appears to have evolutionarily conserved effects on metabolism but not on fecundity or lifespan.

Nonetheless, money continues to flow for this and similar work.

Source:
http://www.fightaging.org/archives/2012/10/metformin-still-dubious-as-a-calorie-restriction-memetic.php

There are numerous ways in which lifestyle choices can damage long-term health and lower life expectancy, but smoking remains one of the more effective, on a par with becoming obese:

The Life Span Study (LSS) was initiated in 1950 to investigate the effects of radiation, tracking over 100,000 people. However, most received minimal radiation exposure, and can therefore provide useful information about other risk factors. Surveys carried out later obtained smoking information for 68,000 men and women, who have now been followed for an average of 23 years to relate smoking habits to survival.

The younger a person was when they started smoking the higher the risk in later life. Older generations did not usually start to smoke until well into adult life, and usually smoked only a few cigarettes per day. In contrast, Japanese born more recently (1920-45) usually started to smoke in early adult life, much as smokers in Britain and the USA.

These differences in smoking habits are reflected in the mortality patterns. Smokers born before 1920 lost just a few years. In contrast, men born later (1920-45) who started to smoke before age 20 lost nearly a decade of life expectancy, and had more than double the death rate of lifelong non-smokers, suggesting that more than half of these smokers will eventually die from their habit. Results on the few women who had smoked since before age 20 were similar.

In addition to studying the risk of smoking, the researchers were able to examine the benefits of stopping. As elsewhere, those who stopped smoking before age 35 avoided almost all the excess risk among continuing smokers, and even those who stopped around age 40 avoided most of it.

Link: http://www.eurekalert.org/pub_releases/2012-10/bmj-st1102412.php

Source:
http://www.fightaging.org/archives/2012/10/the-cost-of-smoking.php

Microbes in the digestive system seem to have some influence on aging, insofar as they interact with the immune system, epigenetic regulation of nearby tissues, and so forth. In effect they act almost like an additional organ or biological system. Researchers are very much in the early stages of trying to understand how microbial life in the body fits in to the bigger picture of metabolism and aging - which is already very complex, and likely to become more so:

The ageing process affects the human gut microbiota phylogenetic composition and its interaction with the immune system. Age-related gut microbiota modifications are associated with immunosenescence and inflamm-ageing in a sort of self-sustaining loop, which allows the placement of gut microbiota unbalances among both the causes and the effects of the inflamm-ageing process.

Even if, up to now, the link between gut microbiota and the ageing process is only partially understood, the gut ecosystem shows the potential to become a promising target for strategies able to contribute to the health status of older people. In this context, the consumption of pro/prebiotics may be useful in both prevention and treatment of age-related pathophysiological conditions, such as recovery and promotion of immune functions ... Moreover, being involved in different mechanisms which concur in counteracting inflammation, such as down-regulation of inflammation-associated genes and improvement of colonic mucosa conditions, probiotics have the potentiality to be involved in the promotion of longevity.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23079287

Source:
http://www.fightaging.org/archives/2012/10/gut-microbes-in-aging.php

Chronic inflammation is a bad thing, walking hand in hand with the frailties and degenerations of aging. Rising inflammation contributes to a very broad range of fatal age-related conditions, and the progressive decline of the immune system itself causes ever greater chronic inflammation, even as it fails to protect the body from pathogens and errant cells. Further, visceral fat tissue is a potent source of inflammation, and this is one of the mechanisms thought to link excess fat with lowered life expectancy and greater risk of age-related disease.

There is plenty in the Fight Aging! archives on the subject of inflammation and its role in aging. To pick a handful of examples:

• Avoid Chronic Inflammation
• Inflammation and the Damage of Aging
• The Importance of Inflammation in Aging
• More Visceral Fat Means More Inflammation
• Inflammation and Life Span Differences Between Species

Some of the best known genetically engineered mutant mice with extended longevity are those in which growth hormone and its receptor are suppressed. They are small, need careful husbanding because they don't generate enough body heat to survive well on their own, and live 60-70% longer than ordinary members of their species. As noted in the following review paper, reduced inflammation has some role to play in this extended healthy life span:

Growth hormone, inflammation and aging:

The last 200 years of industrial development along with the progress in medicine and in various public health measures had significant effect on human life expectancy by doubling the average longevity from 35-40 to 75-80. There is evidence that this great increase of the lifespan during industrial development is largely due to decreased exposure to chronic inflammation throughout life. There is strong evidence that exposure of an individual to past infections and the levels of chronic inflammation increase the risk of heart attack, stroke and even cancer.

Centenarians represent exceptional longevity in human populations and it is already known that many of these individuals are escaping from major common diseases such as cancer, diabetes etc. There is ongoing interest in investigating the mechanisms that allow these individuals to reach this exceptional longevity. There are several animal mutants used to study longevity with hope to determine the mechanism of extended lifespan and more importantly protection from age related diseases. In our laboratory we use animals with disruption of growth hormone (GH) signaling which greatly extend longevity.

Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals.

During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines.

This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

Source:
http://www.fightaging.org/archives/2012/10/on-inflammation-in-mouse-longevity-mutants.php

Videos of the presentations given at this year's Singularity Summit have yet to emerge online, but while we're waiting here is a report on the event:

Kurzweil took the stage on Saturday afternoon to deliver the summit's keynote address. "The singularity is near," he began quietly, a grin slowly spreading across his face. "No, it isn't here yet, but it's getting nearer," he said to laughs and applause. He spoke extemporaneously for over an hour, his presentation a mix of statistics, time series graphs, personal anecdotes, and predictions.

Computing ability and technological innovation have been increasing exponentially over the past few decades, he argued, alongside similar increases in life expectancy and income. "All progress stems from the law of accelerating returns," he proclaimed. He discussed his latest project - an attempt to reverse-engineer the human brain. "Intelligence is at the root of our greatest innovations: genetics, nanotechnology, and robotics. Once we master artificial intelligence, unimaginable new frontiers will open up."

After his talk, a man stood up and looked Kurzweil in the eye. "I'm in my 60s like you," he said, his voice faltering. "Do you think we'll make it?" It took me a few seconds to realize they were talking about immortality and I felt chills in that moment. "Life expectancy tables are based on what happened in the past," responded Kurzweil without skipping a beat. "In 25 years, we'll be able to add one year of life for every year that passes. We have a very good chance of making it through."

I should note that I believe Kurzweil's timelines for rejuvenation biotechnology are only possible if $300 million or more in dedicated research funding turns up at the SENS Foundation's front door tomorrow, thereby ensuring a good shot at demonstrating rejuvenation in old laboratory mice by the mid-2020s. As things stand progress towards the necessary technologies is far slower - not because it cannot be done, but because there is comparatively little interest in doing it, and therefore little funding.

One of the deep puzzles of our age is how a multi-billion-dollar "anti-aging" industry, full of enthusiasm but providing nothing that significantly impacts aging, can exist alongside the near absence of interest in funding research that will produce therapies capable of reversing the progression of aging. There are strange tides at work in the psychology surrounding aging and longevity.

Link: http://www.policymic.com/articles/16546/human-immortality-singularity-summit-looks-forward-to-the-day-that-humans-can-live-forever

Source:
http://www.fightaging.org/archives/2012/10/reporting-on-the-2012-singularity-summit.php

Many dubious arguments are fielded in support of aging and involuntary death: every status quo, no matter how terrible, gathers its supporters. This is one of the deeper flaws inherent in human nature, the ability to mistake what is for the most desirable of what is possible. A hundred thousand deaths each and every day and the suffering of hundreds of millions is the proposal on the table whenever anyone suggests that human aging should continue as it is.

Massive campaigns of giving and social upheaval have been founded on the backs of a hundredth of this level of death and pain - but the world has a blindness when it comes to aging. Such is the power of the familiar and the long-standing: only heretics seek to overturn it, no matter how horrid and costly it is.

Nonetheless, this is an age of biotechnology in which aging might be conquered. There are plans and proposals, set forth in some detail, and debate over strategy in the comparatively small scientific community focused on aging research. So arguments over whether the development of means of rejuvenation should take place at all, reserved for philosophers and futurists in the past, now have concrete consequences: tens of millions of lives and untold suffering whenever progress is delayed. It should always be feared that a society will somehow turn to block or impede research into therapies for aging - worse and more outright crimes have been committed in the past by the members of so-called civilized cultures.

One of the arguments put forward in favor of a continuation of aging and mass death is that without the threat of impending personal extinction we'd collapse into stagnation and indolence. As the argument goes, only death and an explicitly limited future gives us the incentive to get anything done, and so all progress depends upon aging to death. I state the proposition crudely, but this is the essence of the thing, flowery language or no.

This is a terribly wrong way of looking at things: it denies the existence of desire independent of need. It casts us as nothing more than some form of Skinner box, unable to act on our own. This is another example of the way in which many humans find it hard to look beyond what is to see what might be: we live in a state of enforced urgency because we are all dying, because the decades of healthy life are a time of frantic preparation for the decline and sickness that comes later. It is normal, the everyday experience, for all of us to know we are chased by a ticking clock, forced to put aside the things that we would rather do in favor of the things that we must do. We cannot pause, cannot follow dreams, cannot stop to smell the roses.

Some people seem to manage these goals, but only the lucky few - and then only by twining what they would like to do with what they must do. It's hard to achieve that end, and it is really nothing more than an ugly compromise even when obtained. Yet like so much of what we are forced into by the human condition, it is celebrated. One more way in which what is triumphs over what might be in the minds of the masses.

Given many more healthy years of life in which to do so, we would lead quite different lives. Arguably better lives, not diverted by necessity into a long series of tasks we do not want to undertake, carried out for the sake of what will come. We could follow desire rather than need: work to achieve the aims that we want to achieve, not those forced on us. Because of aging and death, we are not free while we are alive - and in any collection of slaves there are those who fear the loss of their chains. The longer they are enslaved, the less their vision of freedom. Sadly, in the mainstream of our culture, it is those voices that speak the loudest.

Source:
http://www.fightaging.org/archives/2012/10/putting-aside-what-youd-rather-do-because-youre-dying.php

Tissue engineers have been inching closer to building a kidney from stem cells in the past couple of years. Here is a recent example of the ongoing work in this field:

Investigators can produce tissues similar to immature kidneys from simple suspensions of embryonic kidney cells, but they have been unsuccessful at growing more mature kidney tissues in the lab because the kidneys' complicated filtering units do not form without the support of blood vessels.

Now, from suspensions of single kidney cells, [researchers] have for the first time constructed "organoids" that can be integrated into a living animal and carry out kidney functions including blood filtering and molecule reabsorption. Key to their success was soaking the organoids in a solution containing molecules that promote blood vessel formation, then injecting these molecules into the recipient animals after the organoids were implanted below the kidneys. The organoids continued to mature and were viable for three to four weeks after implantation.

Link: http://www.sciencedaily.com/releases/2012/10/121018184850.htm

Source:
http://www.fightaging.org/archives/2012/10/a-small-step-towards-tissue-engineered-kidneys.php

Spermidine has been noted to boost autophagy and promote greater longevity to some degree in laboratory animals. Its activities are in the process of being advanced by some researchers as candidate drug mechanisms for slowing aging. Given that, it makes sense for researchers to investigate spermidine levels in longer lived individuals to see if there is any association:

Polyamines (putrescine, spermidine and spermine) are a family of molecules deriving from ornithine, through a decarboxylation process. They are essential for cell growth and proliferation, stabilization of negative charges of DNA, RNA transcription, translation and apoptosis.

Recently, it has been demonstrated that exogenously administered spermidine promotes longevity in yeasts, flies, worms and human cultured immune cells. Here, using a cross-sectional observational study, we determined whole-blood polyamines levels from 78 sex-matched unrelated individuals divided into three age groups: group 1 (31-56 years, N=26, mean age: 44.6±6.07), group 2 (60-80 years, N=26, mean age: 68.7±6.07) and group 3 (90-106 years, N=26, mean age: 96.5±4.59).

Polyamines total content is significantly lower in group 2 and 3 compared to group 1. Interestingly, this reduction is mainly attributable to the lower putrescine content. Group 2 displays the lowest levels of spermidine and spermine. On the other hand, [nonagenarians and] centenarians (group 3) display significant higher median relative percentage content of spermine with respect to total polyamines, compared to the other groups.

For the first time we report polyamines profiles from whole blood of healthy [nonagenarians and] centenarians, and our results confirm and extend previous findings on the role of polyamines in determining human longevity. However, although we found an important correlation between polyamines levels and age groups, further studies are warranted to fully understand the role of polyamines in determining life-span. Also, longitudinal and nutritional studies might suggest potential therapeutic approaches to sustain healthy aging and to increase human life-span.

Link: http://dx.doi.org/10.1089/rej.2012.1349

Source:
http://www.fightaging.org/archives/2012/10/spermidine-levels-measured-in-centenarians.php

Source:
http://get-healthier.com/roasted-cherry-tomatoes/

Spiced Chocolate Cheesecake Brownie

 

Author:

Kerry Jo Brady

Serves: 2

Prep time: 5 mins

Cook time: 1 min

Total time: 6 mins

Print

 

This is so good! You have to try this!!!!

Ingredients

• Spiced Chocolate Cheesecake Brownie
• 1 packet MF Brownies
• 1 packet MF Spiced Pancakes (regular or cc. pancakes would work too)
• 1 tsp Pumpkin Pie Sugar Free Syrup (this is only ⅙ of a condiment, so I am not counting it)
• 6 TB Water
• 1 TB Cream Cheese (1 healthy fat)
• 1 packet Splenda (1 condiment)

Instructions

1. Mix together the MF Brownie and MF Spiced Pancake mixes. Add 1 teaspoon of sugar free pumpkin spiced syrup and 6 TB of water. Mix together and pour into 2 ramekins. Microwave for 1½ minutes. Take out of ramekin and let cool for about 5 minutes. Mix 1 TB of cream cheese and 1 packet of Splenda together for a topping. Divide cream cheese topping and spread evenly on top of each cake. Enjoy!

Notes

This full recipe makes 2 Medifast meals, 1 condiment & 1 healthy fat. Each cake is 1 Medifast meal, ½ condiment and ½ healthy fat serving.

3.1.09

Source:
http://get-healthier.com/spiced-chocolate-cheesecake-brownie/

Some of the effects of aging are driven by signaling changes in important parts of our biochemistry - such as in stem cell niches, collections of cells that provide necessary support to the stem cells that maintain and repair tissue. Niches increasingly act to suppress the stem cells they contain in response to rising levels of cellular and other damage connected to aging. The stem cells themselves also suffer damage, and this evolved response is likely a way to minimize the risk of cancer at the cost of maintaining tissues, but the declining function of the stem cells so far seems to be far more a property of signals from the niche.

In the course of investigating this and similar effects, researchers have been moving blood between young and old mice. Transfusions and joining the bloodstreams of young and old mice are a way to change the signaling environment in order to see what the effects are. The outcome is that a range of measures of aging are reversed:

Experiments on mice have shown that it is possible to rejuvenate the brains of old animals by injecting them with blood from the young. ... blood from young mice reversed some of the effects of ageing in the older mice, improving learning and memory to a level comparable with much younger animals.

[Researchers] connected the circulatory systems of an old and young mouse so that their blood could mingle. This is a well-established technique used by scientists to study the immune system called heterochronic parabiosis. When [researchers] examined the old mouse after several days, [they] found several clear signs that the ageing process had slowed down. The number of stem cells in the brain, for example, had increased. More important, [they] found a 20% increase in connections between brain cells.

One of the main things that changes with ageing are these connections, there are a lot less of them as we get older. That is thought to underlie memory impairment - if you have less connections, neurons aren't communicating, all of a sudden you have [problems] in learning and memory. ... the young blood most likely reversed ageing by topping up levels of key chemical factors that tend to decline in the blood as animals age. Reintroduce these and [all] of a sudden you have all of these plasticity and learning and memory-related genes that are coming back.

Link: http://www.guardian.co.uk/science/2012/oct/17/young-blood-reverse-effects-ageing

Source:
http://www.fightaging.org/archives/2012/10/more-on-young-blood-and-old-mice.php

Source:
http://get-healthier.com/roasted-salmon-with-green-herbs/

Source:
http://get-healthier.com/asian-turkey-burgers/

Much like mammals, bivalve molluscs exhibit a very wide range of life spans. At the known outer end stands the arctic quahog at more than four centuries, and much studied in recent years so as to understand the roots of its longevity. That research project is still ongoing, as are similar comparative studies of aging and longevity in a range of other species.

Here, researchers compare resistance to various forms of physical stress and damage in different bivalve species. As you might expect from the view of aging put forward earlier today, longer-lived species are more resistant to most forms of damage:

Bivalve molluscs are newly discovered models of successful aging. Here, we test the hypothesis that extremely long-lived bivalves are not uniquely resistant to oxidative stressors (eg, tert-butyl hydroperoxide, as demonstrated in previous studies) but exhibit a multistress resistance phenotype.

We contrasted resistance (in terms of organismal mortality) to genotoxic stresses (including topoisomerase inhibitors, agents that cross-link DNA or impair genomic integrity through DNA alkylation or methylation) and to mitochondrial oxidative stressors in three bivalve mollusc species with dramatically differing life spans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and the Atlantic bay scallop, Argopecten irradians irradians (maximum species life spans: more than 500, more than 100, and ~2 years, respectively).

With all stressors, the short-lived A i irradians were significantly less resistant than the two longer lived species. Arctica islandica were consistently more resistant than M mercenaria to mortality induced by oxidative stressors as well as DNA methylating agent nitrogen mustard and the DNA alkylating agent methyl methanesulfonate. The same trend was not observed for genotoxic agents that act through cross-linking DNA. In contrast, M mercenaria tended to be more resistant to epirubicin and genotoxic stressors, which cause DNA damage by inhibiting topoisomerases.

To our knowledge, this is the first study comparing resistance to genotoxic stressors in bivalve mollusc species with disparate longevities. In line with previous studies of comparative stress resistance and longevity, our data extends, at least in part, the evidence for the hypothesis that an association exists between longevity and a general resistance to multiplex stressors, not solely oxidative stress.

In mammals, you might look to the naked mole rat as an analogous species: very resistant to all sorts of biological and cellular damage, and extremely long-lived in comparison to similar sized rodent species.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23051979

Source:
http://www.fightaging.org/archives/2012/10/comparing-longevity-and-damage-resistance-in-bivalves.php

So the future of medicine is golden, biotechnology is in the throes of a vast expansion of capabilities and free-fall in costs, and we have a good idea as to how to go about reversing aging - if the research community would just stop tinkering with efforts to merely slow down aging and get on with achieving the all-round better goal of rejuvenation. We should all donate money and time to help out, because it's not as though we can take it with us and irreplaceable time is ticking away. A shot at lifespans of centuries and longer is coming, with not so much time left in which to reach for that goal.

Putting all of that to one side for the moment, there is the arguably less important question of how to optimize heath and life span given the present poor tools to hand. Many people spend a great deal of time talking and debating on this topic, immersing themselves in the world of what presently exists, and giving little thought to what might lie ahead. A vast industry caters to people who think they've found the better mousetrap when it comes to personal health and aging. They're all wrong, of course, but that doesn't stop the flow of commerce.

The sad truth of the matter is that it's simple and easy to achieve the 80/20 result in health and longevity within the bounds of the tools we have available to us today, provided you're starting out as a basically ordinary, healthy individual. Exercise regularly, the 30 minutes daily of aerobic exercise that has been recommended by physicians since way back when, and practice calorie restriction with optimal nutrition - i.e. eat a sane diet, not very much of it, and obtain the necessary levels of micronutrients while doing so. There's also the matter of not harming yourself greatly, but just as I shouldn't have to mention avoidance of knives and falling rocks, I shouldn't have to mention things like giving up smoking.

These things are not rocket science. They are widely known and most have been advocated for centuries. The supporting statistical data is far better now than at any point in the past, and so you have no excuses: if you're not adopting these practices then it is because you have decided to accept a shorter life expectancy and greater odds of ill health in exchange for the dissipations that you presently enjoy. No-one's perfect, right?

But here is an interesting thing about trying to reliably forge ahead beyond the 80/20 point in personal health, in search of the optimum level of improvement: it's next to impossible to go further or reliably measure that you have gone further. The research community has expended billions without being able to determine how you can do that - so what makes you think that you can do any better given your far more limited resources? Metabolism and its interactions are so very, very complex. We can list with some confidence what is good for you, but talking about what is optimal is far beyond present capabilities.

For example, to pick one line item, let us consider calorie restriction. It works amazingly well in short-lived animals and improves short-term measures of human health far more than any presently available medical technology can manage. But once we get to an examination of longer lived animals (such as we primates) over the long term, it starts to become much harder to pin down the best, most optimal way to do things - certainly, the present primate studies are beginning to look as though they will generate as much ambiguity as data.

Dietary Restriction: critical cofactors to separate healthspan from lifespan benefits

Dietary restriction (DR), typically a 20-40% reduction in ad libitum or "normal" nutritional energy intake, has been reported to extend lifespan in diverse organisms including yeast, nematodes, spiders, fruit flies, mice, rats and rhesus monkeys. The magnitude of the lifespan enhancement appears to diminish with increasing organismal complexity. However, the extent of lifespan extension has been notoriously inconsistent, especially in mammals.

Recently, Mattison et al. report that DR does not extend lifespan in rhesus monkeys in contrast to earlier work of Colman et al. Examination of these papers identifies multiple potential confounding factors. Among these are the varied genetic backgrounds and composition of the "normal" and DR diets. In the monkeys, the correlation of DR with increased healthspan is stronger than that seen with lifespan, and indeed may be separable. Recent mechanistic studies in Drosophila implicate non-genetic cofactors such as level of physical activity and muscular fatty acid metabolism in the benefits of DR. These results should be followed up in mammals. Perhaps levels of physical activity among the cohorts of rhesus monkeys contributes to inconsistent DR effects.

To understand the maximum potential benefits from DR requires differentiating fundamental effects on aging at the cellular and molecular levels from suppression of age-associated diseases, such as cancer. To that end, it is important that investigators carefully evaluate the effects of DR on biomarkers of molecular aging, such as mutation rate and epigenomic alterations. Several short-term studies show that humans may benefit from DR in as little as 6 months, by achieving lowered fasting insulin levels and improved cardiovascular health.

Optimized healthspan engineering will require a much deeper understanding of DR.

That last sentence is worth considering at length - but remember that the 80/20 win for personal health is still right here, easily achieved. Instead of trying to go further in a presently impossible attempt at optimization, a better use of that time and energy lies in supporting research and development of rejuvenation biotechnology. Even a magically optimized personal health program would not allow most people to live to 100 with today's technology - the only way that the vast majority of us will get to see a three digit birthday cake is through progress in longevity science and its clinical applications.

So if you're going to spend any effort on this whole living longer in good health thing, spend it wisely. Don't chase rainbows.

Source:
http://www.fightaging.org/archives/2012/10/achieving-the-8020-point-in-general-health-is-easy-but-anything-more-is-near-impossible.php

Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.

Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.

Source:
http://get-healthier.com/this-is-an-snack-post-2/

One line of research into treatments for neurodegenerative disorders involves spurring the brain to establish new neural connections to replace those that have been damaged or lost. This seems like an inferior strategy in comparison to trying to identify and remove root causes, one that can only delay the inevitable, but it's nonetheless a fairly entrenched field of work.

Here is an example of this sort of research - and note that as for other similar efforts there are hints that an induced increase in neural plasticity would be beneficial for cognitive function in all older individuals:

Researchers have developed a new drug candidate that dramatically improves the cognitive function of rats with Alzheimer's-like mental impairment. Their compound, which is intended to repair brain damage that has already occurred [by] rebuilding connections between nerve cells.

[The scientists] have been working on their compound since 1992, when they started looking at the impact of the peptide angiotensin IV on the hippocampus, a brain region involved in spatial learning and short-term memory. ... angiotensin IV, or early drug candidates based on it, were capable of reversing learning deficits seen in many models of dementia. The practical utility of these early drug candidates, however, was severely limited because they were very quickly broken down by the body and couldn't get across the blood-brain barrier.

Five years ago, [the scientists] designed a smaller version of the molecule [called] Dihexa. Not only is it stable but it can cross the blood-brain barrier. An added bonus is it can move from the gut into the blood, so it can be taken in pill form. The researchers tested the drug on several dozen rats treated with scopolamine, a chemical that interferes with a neurotransmitter critical to learning and memory. Typically, a rat treated with scopolamine will never learn the location of a submerged platform in a water tank, orienting with cues outside the tank. After receiving the [drug], however, all of the rats did, whether they received the drug directly in the brain, orally, or through an injection.

[The researchers] also reported similar but less dramatic results in a smaller group of old rats. In this study the old rats, which often have difficulty with the task, performed like young rats. While the results were statistically valid, additional studies with larger test groups will be necessary to fully confirm the finding.

Link: http://www.eurekalert.org/pub_releases/2012-10/wsu-pad101012.php

Source:
http://www.fightaging.org/archives/2012/10/treating-neurodegeneration-by-increasing-neural-plasticity.php

Stem cell therapies offer all sorts of possible ways to intervene in disorders of the brain and nervous system: the evidence suggests that, as for other parts of the body, there is a lot that can be achieved by dropping in a bunch of fully functional cells of the right type and letting them get to work. Or, alternately, by finding ways to stimulate existing cell populations into working harder.

Most of these approaches fall into the category of patches: increasing the pace of repair and recreation of destroyed resources, but doing little to address the underlying reasons for damage and destruction. As a strategy this is second-rate, especially in the brain, but it is how the mainstream of medical research proceeds. In part we can blame regulatory bodies for the focus on patching end results rather than preventing root causes: the way in which requirements and costs are imposed on the development of new therapies leads to a situation in which it the less expensive (and in some cases only) path is to build treatments for late stage disease.

Damage to myelin, the sheathing for axons in nerve cells, is at the root of a number of serious medical conditions. As is the case for most of our biology the integrity of myelin declines with age; some fraction of the age-related decline in cognitive function that occurs for everyone is thought to stem from progressively less effective myelination in the brain. A number of research groups are engaged in ongoing work with stem cells aimed at the repair of myelin, and here is one example:

Stem Cells Myelinate Human Brain

Neural stem cells transplanted into the brains of people with Pelizaeus-Merzbacher disease (PMD) can differentiate and begin producing the myelin sheaths that these patients lack, according to results of a Phase I clinical trial. ... If the stem cell transplants do ultimately demonstrate benefit, they could help more than just PMD patients ... There's a wide range of possible myelin disorders that could be targeted, including demyelinating disorders like multiple sclerosis and preterm babies at risk for cerebral palsy due to white matter injury.

Here, as in many other cases, a therapy is under development for use with specific named diseases - but it might also prove helpful as a treatment for aging, as an attempt to retard loss of cognitive function. Yet there is no path to legally produce therapies for general use in all old people in the US: the FDA doesn't recognize treatment of aging as a legitimate use of medicine, and short a revolution there's little hope of changing that situation through existing paths. Until this changes, a great deal of promising work will be sidetracked into narrow usage for late stage specific diseases, and any real progress towards clinical applications for aging will have to happen outside the US research community.

Source:
http://www.fightaging.org/archives/2012/10/stem-cell-transplants-as-a-way-to-regenerate-myelin.php

Here is a framework for thinking about aging and longevity: various forms of low-level biological damage accrue as a result of the operation of metabolism, degrading organs and tissues and ultimately causing death. Where natural selection favors longer-lived individuals, mechanisms will evolve to repair, minimize, or resist the effects of this damage. So aging is driven by damage, but genetic programs interact with that damage, evolved to try to do something about it.

Thus we could expect to be able to manipulate life span either by repairing damage or by altering the programs. The former approach should produce far more effective means of healthy life extension, however, including rejuvenation of the old. In comparison, and from what we've seen so far in longevity science, modestly slowing aging is about the best we can expect from the near future of genetic and metabolic alterations.

In spite of exciting new insights into regulatory mechanisms that modulate the aging process, the proximal cause of aging remains one of the unsolved big problems in biology. An evolutionary analysis of aging provides a helpful theoretical framework by establishing boundary conditions on possible mechanisms of aging. The fundamental insight is that the force of natural selection diminishes with age. This does not preclude senescence (age-related decrease in individual fitness) from occurring in natural populations. Senescence can develop because some genes have non-separable, but typically different or opposite, functions in reproductive-age and in old individuals. Such genes, selected according to their "youthful" function, may thus impose a distinct senescent phenotype in old age.

In general, however, unless a controversial formulation of group selection is invoked, traits that would become manifest only in old age cannot evolve. This precludes the evolutionary emergence of aging programs, which have been sometimes postulated to exist in analogy to developmental and other biological programs. (By the same token, selective pressure that diminishes with age would also prevent extreme longevity from evolving, if "extreme" denotes a potential life span much longer than that imposed by extrinsic mortality in a given environment.) This and other arguments against the existence of an aging program have been discussed previously.

The evolutionary perspective sketched out above does not specify the mechanisms that underlie aging, but it helps to narrow down the possibilities. As already discussed, an evolved deterministic aging program can be ruled out, perhaps with the exception of specific niche situations. In the absence of adaptive life-curtailing processes driven by a putative aging program, we are left with untargeted pro-aging, destabilizing phenomena which, in principle, may range from purely stochastic to side-effects of "legitimate" biochemical pathways. These destabilizing forces are counteracted by evolved, and genetically controlled, longevity assurance (or repair/maintenance) processes. The interplay of these countervailing forces determines the life span.

While I have previously presented my detailed interpretation of this model, its central tenets bear repeating: (a) the destabilizing processes that drive aging are neither evolved nor adaptive; (b) in contrast, longevity assurance mechanisms are under genetic control; (c) together, these two opposing forces determine life span; (d) the average life span of a species is set by evolving longevity assurance mechanisms so as to optimize reproductive success under environmental conditions typical for that species.

Link: http://dx.doi.org/10.3389/fgene.2012.00189

Source:
http://www.fightaging.org/archives/2012/10/considering-longevity-in-terms-of-damage-versus-damage-repair.php