Confounding Factors Abound

It is now fairly well known that any animal study of longevity has to be controlled for calorie restriction, as the effects of even a modest change in dietary intake can outweigh the intended effects of the study, rendering the results useless. This is far from the only confounding factor out there, however. Here is some work on a different issue that might be problematic for longevity studies in worms: "The nematode worm Caenorhabditis elegans has been used to identify hundreds of genes that influence longevity and thereby demonstrate the strong influence of genetics on lifespan determination. In order to simplify lifespan studies in worms, many researchers have employed 5-fluoro-2'-deoxyuridine (FUdR) to inhibit the development of progeny. While FUdR has little impact on the lifespan of wild-type worms, we demonstrate that FUdR causes a dramatic, dose-dependent, twofold increase in the lifespan of the mitochondrial mutant gas-1. Thus, the concentration of FUdR employed in a lifespan study can determine whether a particular strain is long-lived or short-lived compared to wild-type." This sort of thing is one of the many reasons why it is better to weigh evidence across many studies and to be skeptical of any one study in isolation.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21893079

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A Primer on Compression of Morbidity

If you spend much time reading around the topic of aging, human longevity, and medical progress, you'll soon run into the term "compression of morbidity." It is a hypothesis suggesting that advances in medical science are causing, or will cause, a compression of the terminal period of frailty, illness, and disability at the end of life, squeezing it into an ever-shorter fraction of the overall human life span. In colloquial use compression of morbidity is spoken of as a practical goal by medical researchers who do not wish to talk openly about extending human life for political or funding reasons. To my eyes the concept of compression of morbidity is rather too tied up with the self-defeating way in which gerontologists behaved with respect to human longevity for so many years: it makes it hard to discuss without pulling in the recent history of politics, funding organizations, and strategic debates within the aging research community. Some background from the archives can be found in the following posts:

Compression of morbidity as a concept also touches on debates and initiatives to persuade more of the research community to adopt repair-based research strategies such as SENS. These repair-based strategies for treating - and ultimately reversing - aging emerge fairly directly from the viewpoint that aging is little more than the effects of damage accumulation at the level of our cellular and molecular protein machinery. If you look at the body as a complex system that gathers damage, such as through the lens of reliability theory, compression of morbidity begins to seem a mirage of sorts. Any intervention that can slow or repair some of the biological damage that causes aging will extend life but not do much for the period of decline at the end - it just puts it off. This is the same for any machine. If you learn how to repair biological damage sufficiently comprehensively then you could put off that final decline indefinitely, which is the SENS goal. But if you stopped undergoing those periodic repairs, then you'd age just the same way and at the same pace as someone who never had the treatment.

But to return to the point of this post, which is to introduce the concept of compression of morbidity, I should mention that I stumbled across a good introductory open access paper today, written for a general audience by the originators of the compression of morbidity hypothesis. You might find it interesting:

Compression of Morbidity 1980-2011: A Focused Review of Paradigms and Progress

The Compression of Morbidity hypothesis - positing that the age of onset of chronic illness may be postponed more than the age at death and squeezing most of the morbidity in life into a shorter period with less lifetime disability - was introduced by our group in 1980. This paper is focused upon the evolution of the concept, the controversies and responses, the supportive multidisciplinary science, and the evolving lines of evidence that establish proof of concept.

Dive in and see what you think. The authors believe the data of the past decades illustrates that compression of morbidity is in fact occurring, and that improvement in the rate is possible given that no structured effort was expended towards this goal over that time. You might look at an older post here for a alternate explanation of the data with more of a damage-based view. No-one is arguing against the trend towards increasing life expectancy in the old and falling mortality rates for age-related diseases, but there is plenty of argument when it comes to the root causes of that trend - and therefore how to improve on it.

Source:
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Spinal Fusion Through Stem Cells

A modest new application of stem cells in therapy: researchers "have used a new, leading-edge stem cell therapy to promote the growth of bone tissue following the removal of cervical discs - the cushions between the bones in the neck - to relieve chronic, debilitating pain. [The procedure] used bone marrow-derived adult stem cells to promote the growth of the bone tissue essential for spinal fusion following surgery, as part of a nationwide, multicenter clinical trial of the therapy. ... We hope that this investigational procedure eventually will help those who undergo spinal fusion in the back as well as in the neck, and the knowledge gained about stem cells also will be applied in the near future to treat without surgery those suffering from back pain. ... In the surgery, called an anterior cervical discectomy, a cervical disc or multiple discs are removed via an incision in the front of the neck. The investigational stem cell therapy then is applied to promote fusion of the vertebrae across the space created by the disc removal. ... [Using existing methods], adequate spinal fusion fails to occur in 8 to 35 percent or more of patients, and persistent pain occurs in up to 60 percent of patients with fusion failure, which often necessitates additional surgery. ... A lack of effective new bone growth after spine fusion surgery can be a significant problem, especially in surgeries involving multiple spinal segments. This new technology may help patients grow new bone, and it avoids harvesting a bone graft from the patient's own hip or using bone from a deceased donor."

Link: http://www.sciencedaily.com/releases/2011/09/110906152501.htm

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

Carving Named Diseases From the Concept of Aging

Seen from a considered distance, the culture of aging research - formed of researchers, regulators, and the interested public - operates in strange ways. No-one is permitted to treat aging: by decree of the regulators and complicity of the researchers that is taboo. But slow progress in treating aging is made nonetheless. That technological progress goes hand in hand with an intricate cultural dance that consists of splitting off pieces of the concept of aging and giving each piece a different and distinct name ("Alzheimer's disease," "osteoarthritis," "sarcopenia," and so forth). Once such a sliver of aging is named and fully accepted, it is no longer taboo to work towards treating it.

To a certain degree, culture shapes the progress of medical science. Strategies for repairing aging outright by focusing on common low-level molecular changes - like Engineered Negligible Senescence - don't mesh well with the structure of the mainstream culture of aging research, and so face an uphill battle to win greater adoption. Repair strategies do away with the whole business of parceling up a collection of end-stage symptoms of aging and declaring them a disease, and focus instead on a different vision for aging and the treatment of aging from the bottom up. Long-standing cultures are resistant to change, however, and especially resistant to radical change. That is far from the only hurdle in the way of progress, and the existence of centralized control over medicine and heavy regulation has a lot more to answer for than odd cultural ideas about how things should work, but those odd ideas are still a factor.

You can see some of this business of carving slivers from the concept of aging in a recently published retrospective article on research into the biology of neurodegenerative diseases:

Only 40 years ago it was widely believed that if you lived long enough, you would eventually experience serious cognitive decline, particularly with respect to memory. The implication was that achieving an advanced age was effectively equivalent to becoming senile - a word that implies mental defects or illness. ... Many discoveries made in the years since have given us better tools to study memory storage, resulting in a major shift away from the view of "aging as a disease" and towards the view of "aging as a risk factor" for neurological diseases. So why do some people age gracefully, exhibiting relatively minor - and at worst annoying - cognitive changes, while others manifest significant and disabling memory decline? Answers to these questions are fundamental for understanding both how to prevent disease and how to promote quality of life.

...

Looking back on the rather grim expectations concerning memory and the elderly that were held only a few decades ago, the vision today is very different and much more positive. ... The future holds great promise for the once remote dream of understanding the core biological processes required for optimal cognitive health during aging - and progress in this regard should also provide the needed backdrop for understanding and preventing the complex neurological diseases that can be superimposed on the aging brain.

The culture of the aging and broader life science research community is appropriately intricate: it's a large industry, working on exceedingly complex problems. But don't uncritically accept it for what it is; it never hurts to take a second look from a suitable distance and ask whether what you see is all that is possible, and whether it is good, useful, worse, or better than other plausible options.

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

A Metastudy on Exercise and Dementia

Via EurekAlert!: "Any exercise that gets the heart pumping may reduce the risk of dementia and slow the condition's progression once it starts ... Researchers examined the role of aerobic exercise in preserving cognitive abilities and concluded that it should not be overlooked as an important therapy against dementia. The researchers broadly defined exercise as enough aerobic physical activity to raise the heart rate and increase the body's need for oxygen. Examples include walking, gym workouts and activities at home such as shoveling snow or raking leaves. ... We culled through all the scientific literature we could find on the subject of exercise and cognition, including animal studies and observational studies, reviewing over 1,600 papers, with 130 bearing directly on this issue. We attempted to put together a balanced view of the subject. We concluded that you can make a very compelling argument for exercise as a disease-modifying strategy to prevent dementia and mild cognitive impairment, and for favorably modifying these processes once they have developed. ... The researchers note that brain imaging studies have consistently revealed objective evidence of favorable effects of exercise on human brain integrity. Also, they note, animal research has shown that exercise generates trophic factors that improve brain functioning, plus exercise facilitates brain connections (neuroplasticity). ... Whether addressing our patients in primary care or neurology clinics, we should continue to encourage exercise for not only general health, but also cognitive health."

Link: http://www.eurekalert.org/pub_releases/2011-09/mc-aem090711.php

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

More Autophagy Research

Autophagy is important in longevity, and research groups are investigating this process with an the intent of developing ways to safely manipulate it: "two cellular processes - lipid metabolism and autophagy - work together to influence worms' lifespan. Autophagy, a major mechanism cells use to digest and recycle their own contents, has become the subject of intense scientific scrutiny over the past few years, particularly since the process (or its malfunction) has been implicated in many human diseases, including cancer and Alzheimer's disease. This study provides a more detailed understanding of the roles autophagy and lipid metabolism play in aging. ... The particular worm model we used in this study is known to live longer than normal worms, but we didn't completely understand why. Our results suggest that increased autophagy has an anti-aging effect, possibly by promoting the activity of a fat-digesting enzyme. In other words, it seems that recycling fat is a good thing - at least for worms. ... When worms have more fat in supply than they have demand for, it has to be stored. In these long-lived worms however, there's activation of a seemingly futile cycle of breaking down fat and re-synthesizing it. Only we found that breaking down fat is actually beneficial and perhaps not so futile after all. ... On average, they survived 25 percent longer than their normal counterparts."

Link: http://www.eurekalert.org/pub_releases/2011-09/smri-rfm083111.php

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

Epigenetics of Calorie Restriction

An open access review paper in PDF format that discusses some of the fine details of current research into the mechanisms by which calorie restriction slows aging. This work is aimed at establishing a level of understanding sufficient to produce calorie restriction mimetic drugs that also slow aging: "The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors and caloric restriction is by far the most effective and established environmental manipulation for extending the lifespan of various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modifications, are believed to dynamically influence the chromatin structure resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulations in response to caloric restriction and how this impacts cellular senescence, aging and potential extension of a healthy lifespan for humans. Enhanced understanding of the important role of epigenetics in control of aging through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases."

Link: http://www.biomedcentral.com/1741-7015/9/98

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

Perhaps the Cryonics Industry Needs a Luxury Line

Industries are rather like certain forms of insect - they go through characteristic stages in their life cycle in which the look, internals, and behavior are very different. Moving from one stage to the next is a matter of growth: gaining customers, revenue, mindshare, and the funds for significant research and development. Industries start out as advocacy projects - a few people who think they're right, and have the necessary luck, skill, and staying power to convince a market into their way of thinking. In those early stages, the dynamic between leaders and followers is very different than it is in mature industries. There is a lot of passion and zealotry, people doing things for love rather than money, active advocates with strong opinions and no fear of shouting them out loud. Lots of drama, excitement, and rapid change. But as an industry grows into its later stages, and the number of customers swell, that passion and zealotry fades into the background, to be replaced by the quiet hum of businesses that are all about professionalism, standards, reassuring public faces, steady wages, and long term profits. Look at the personal computer industry, for example - it's no coincidence that all the good stories and larger than life characters are from the 1970s, back when everyone knew one another and the whole thing was a collection of people in various garages.

The computing industry succeeded, evidently, but the cryonics industry - born around the same time - never made it much beyond the early stages of growth. The reasons for this have been discussed to death over the years, so I won't go into them here, but the industry is presently in that early stage middle ground where staid, long-term business practices and the passion of the zealots are equally present and influential. This has been the case for the past twenty years, and there the industry will stay until there is significant growth in the number of customers: when an industry remains small, there is no chance for the original founders - colorful characters who are passionate enough to set out and do what most people never get around to trying - to fade away in favor of solid bottom-line-and-marketing businessmen. It it stays small for long enough, you end up with a significant fraction of embittered zealots and their drama, which is never fun.

When an initiative does succeed attracting broad support and a large community, the energy and quirks of the early activists are tempered by a sea of more sedate, everyday folk. Sometimes the pioneers are quietly airbrushed out of the official histories - once an initiative becomes large enough for its leaders to want it to look like a shiny, official, professional machine, then the original barnstormers and larger than life personalities start to be seen as a liability. Justifiably or not, they are shuffled to one side of the growing crowd. In this way, the ultimate accolade of success is to be made irrelevant in the movement you helped found: accepting that likelihood up front is the way to peace of mind for activists and advocates.

But when things don't go according to plan, and what was intended to be great fails to achieve its original promise, or moves too slowly, then the problems start. Some of the early activists, untempered by large numbers of new volunteers and supporters, become poisonous. Their hyperactivism manifests itself in perfectionism, attacks on members of the community, and other displays of frustration or bitterness: to their eyes, failure was avoidable, and the problem must be the other people involved.

While you might not think of it as such, given the $100,000+ sticker price on a cryosuspension ordered at short notice, cryonics is actually a service priced for the mass market: people who can plan enough to regularly put aside a little for the long term. Most customers pay for cryonics through life insurance, which when started in middle age is no more than a very modest monthly payment - less than your car payments, perhaps less than your car insurance payments.

There is nothing wrong with that per se, but the industry isn't overcoming the barriers to growth. The most reliable way of pushing through a barrier to growth is investment: large sums of money poured into marketing, research, development and so forth. Those of you who have been involved in young companies will know about barriers to growth: there are times when your venture speeds ahead and customers pour in seemingly of their own accord, and there are times when you hit a brick wall and the only way through is via money - spent on changing the business, spent on marketing, spent on researching how to get past the barrier ... whatever works in the end. But fundamentally, that's what investment in a business is all about: figuring a way past the next brick wall so as to become larger and thus more profitable in absolute terms.

There are two sources of capital for investment: investors and your customers. We'll leave investors out of this discussion, as there are few willing to invest in cryonics. It looks terrible as a money-making proposition, given its history, and the known cryonics-friendly philanthropists are not particularly deep pocketed in the grand scheme of things. Obtaining funding from early customers is a time-honored tradition in many businesses, however: the early customers tend to be wealthy and pay high prices for their early access to a product. The money they provide pays off the debts of prior research and development and funds ongoing growth - this is a part of the process in many industries by which products start out as a costly luxury item and later become a mass-market commodity that is both far cheaper and far better.

Cryonics seems to have skipped the costly luxury item stage in its existence, which is both interesting and possibly a liability for the industry in the long term. One might envisage some form of Cryonics Platinum organization that offers $500,000 or $1 million packages for folk like Simon Cowell, Ted Williams, politicians, and other multimillionaires who can both afford it and have use for the additional services, security, process management, and cachet that a higher price point can supply.

I have no idea whether such a thing is viable, but I don't see any obvious purely economic reason as to why it wouldn't be. It's really little different in structure than, say, the business of long-term leasing of luxury yachts or private jets and their crews. Something to think about.

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

Why Research the Biology of Non-Mammals so Heavily?

A comment from a reader on a recent zebrafish-related news post:

IMO it's a waste of money and scientists. We should only focus on mammals, because humans are no fish. It won't help us much, if at all.

That last assertion is not true, in fact. A great deal of exploratory life science research is first accomplished in species like fruit flies, nematode worms, yeast, zebrafish, and the like. Outside the realm of mammals there exists a small menagerie of species that have proven useful in the laboratory. Yet any of that work to ultimately make it to human clinics will first be repeated or confirmed in mammalian species such as mice, dogs, and primates - which might raise the question as to why researchers bother to work with flies, worms, yeast, and fish in the first place.

The answer to that question relates to the bottom line: money, time, resources. Research is by its very nature an exploratory and uncertain business, full of dead ends and unexpected pitfalls. A researcher wants to cover as much ground as he or she can for a given amount of time and money: the more that is explored, the greater the chance of finding a significant path forward. On the one hand, work with mammals will generally produce more useful information, but on the other hand working with mammals, even mice, is very expensive and time-consuming in comparison to working with flies and worms, which in turn is expensive and time-consuming in comparison to working with yeast. If infinite money and time were at hand, all research work would involve mammals, but resources are not infinite and the results of any given study are extremely uncertain.

Bear in mind that evolution produced flies, yeast, fish, and mammals from the same deep roots - and as it turned out, a lot of the mechanisms that link the operation of metabolism with variance of longevity within a species were (a) established very early on, and (b) then didn't change a great deal. It is counter-intuitive to think that researchers can learn useful things about the operation of human biology from yeast (or worms, or flies, or fish), but for some mechanisms and systems they can do just that. The further away from human biology that your model is, the more inference there must be, and the greater the risk that there is in fact some important difference between species that renders your work useless or less valuable - but that doesn't prevent work in lower species from being cost-effective.

So the story is that there is a trade-off in the life sciences between the usefulness of data and the cost of obtaining that data. When you are uncertain of the ultimate value of the work presently being undertaken - i.e. if it seems to have a high risk of failure, or a successful outcome is probably not that valuable in any case - then you won't want to spent much time and money on it until such time as it shapes up. If all indications show a good chance of success and a valuable result, then working with mammals starts to look like a better prospect, however. So we might say that work in flies, worms, yeast, and fish is undertaken in order to justify the cost of exploring the same biology in mammals.

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

He'll Let Folk Know When the Worm Zapping Commences

You might recall that the Immortality Institute raised funds for a test of laser ablation of lipofuscin, to run on nematode worms using commercially available laser equipment:

The good news for today is that the longevity science grassroots centered at the Immortality Institute have successfully raised $8,000 to fund research into laser ablation of lipofuscin. Those funds will be matched up to $16,000 at the SENS Foundation and put towards work on a method of eliminating one form of damaging metabolic byproducts that build up with age.

Lipofuscin is the name given to a collection of various waste products of metabolism that are hard for the body to break down. They build up inside cells, collecting in the recycling mechanisms of lysosomes and causing cellular housekeeping to progressively fail over time. Ways to safely break down lipofuscin are very much required as a part of the envisaged package of future rejuvenation biotechnology that can prevent and reverse aging.

One proposed methodology for tackling lipofuscin is the use of pulsed laser light targeted at very specific molecules and molecular bonds: in theory, it should be possible to significantly impact lipofuscin levels without harming the cells that contain this gunk. Whether this is the case in practice remains to be seen, but it is an approach well worth testing: after all, lasers are already routinely used in dermatology to achieve conceptually similar goals, and the cost of this test is minimal in the grand scheme of things. Hence the laser ablation project funded by forward-looking donor and organized by the Immortality Institute.

You'll find recent updates on the state of the laser ablation test in the Longecity thread for the project:

Here is the basic agenda for the remainder of the project:

1) Test the effect of 8ns pulses on worm lifespan, at many different intensities. ... The beam coming straight out of the laser has terrific coherence and a nice tophat profile, which although it is 8ns, which is a little harsh, it is wonderfully consistent, great at destroying pigments, and we can rest assured that all worms on the slide are getting the exact same exposure every time.

2) Examine effect on worm activity/livelihood. Since the worms grow distinctively and progressively less active in the 2nd half of their life, this can be used to roughly assess quality of life changes; i.e. if worms are all dying at the same time, but at 75% lifespan, laser-treated groups are still quite active, this could be seen as a definite extension of useful lifespan.

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500

...

4) Assess the effect of laser treatment on a more long-lived strain of worms (such as DAF-16 mutants), as well as the wild-type. This could provide useful clues as to what is going on, whichever way the results go.

...

It's still taking awhile to breed more DA1116 worms. I can see how this is going to go - things are going to stretch out a bit, partly due to my schedule and partly due to using long-lived worms, and the nature of lifespan experiments in general. Therefore I propose using experiments as milestones instead of sticking to a fixed weekly or monthly schedule. Thus the project will span at least 8 complete lifespan experiments, regardless of how long it takes to complete them. The remaining 'monthly' salary and expense checks could be sent at the start of experiments 3, 5 and 7 - which will doubtless end up being more than one month apart. This definitely seems more appropriate to me - that way all of our gracious donors get the same amount of science for their money, regardless of how long it takes.

The fluorescence scope may or may not be purchased for this project, depending on how our financial situation pans out on this end. It may end up being budgeted as part of a future project proposal instead; but we can cross that bridge when we get there.

I'll let everyone know as soon as the worm zapping begins.

One of the Immortality Institute volunteers visited the lab recently, and so you'll find photographs of the equipment, work area, and researcher in the thread to go along with the updates.

By way of a reminder, the Institute continues to raise funding for their next project, an investigation of microglia transplantation as a therapy for age-related neurodegeneration. $5,500 of the needed $8,000 has been raised, and futher donations are very welcome. Every dollar donated will be matched by an additional dollar from the Institute and its sponsors, so that the completed fundraiser will send $16,000 to the laboratory that will carry out the research:

Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia [in mice] with new and young microglia cells derived from adult stem cells.

...

The full PDF format research proposal is available: the work will be carried out by a graduate research assistant and will cost $16,000. This is the essence of our present era of biotechnology: a task that would have occupied a whole laboratory and its equipment in the 1980s, and cost a great deal of money if it was even possible at all, is now something that a skilled graduate-level life scientist can organize and run himself within an established lab.

Creating Inner-Ear Cells

Via EurekAlert: "Humans are born with 30,000 cochlear and vestibular hair cells per ear. (By contrast, one retina harbors about 120 million photoreceptors.) When a significant number of these cells are lost or damaged, hearing loss occurs. The major reason for hearing loss and certain balance disorders is that - unlike other species such as birds - humans and other mammals are unable to spontaneously regenerate these hearing cells. ... After years of lab work, researchers [have] found a way to develop mouse cells that look and act just like the animal's inner-ear hair cells - the linchpin to our sense of hearing and balance - in a petri dish. If they can further perfect the recipe to generate hair cells in the millions, it could lead to significant scientific and clinical advances along the path to curing deafness in the future. ... While researchers will ultimately need human hair cells, the mouse version is a good model for the initial phases of experimentation, he said. In addition to using mouse embryonic stem cells, the researchers used fibroblasts that had been reprogrammed to behave like stem cells: These are known as induced pluripotent stem cells, or iPS cells."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/sumc-at051010.php

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

Lycopene for a Healthy and Beautiful Skin

Consumption of lycopene through tomato paste showed evidence of protecting the skin from excessive reddening caused by exposure to UV rays.

A collaborative study conducted by Newcastle University, the University of Manchester and Salford Royal NHS Foundation Trust, revealed that consumption of foods containing Lycopene reduces the reddening of the skin after long hours of exposure to the sun’s ultraviolet (UV) rays. Tomatoes are the richest known sources of lycopene and heat-treated tomato paste has more lycopene content than fresh raw tomatoes. A small serving of tomato paste contains approximately 16 milligrams of lycopene. Skin reddening brought about by extended exposure to UV rays is caused by the damage to mitochondrial DNA. Sufficient servings of tomato paste on a daily basis protect mitochondrial DNA from damage, thereby reducing skin reddening and keeping the skin healthy. This study was published in the British Journal of Dermatology.

The study on the dermatological benefits of lycopene supports previous findings regarding its protective properties against UV rays and tissue damage. However, the research has only produced preliminary evidence and further research is still needed. Lycopene is also a known antioxidant and the substance has also shown medical evidence for lowering the risk of developing prostate, skin and heart diseases. It is also essential in keeping the bones healthy. While lycopene has been known to be derived naturally from tomatoes, it can also be produced synthetically. As an additional treat, lycopene is also being used in cosmetic and beauty products, and in food supplements.

The lycopene study consisted of twenty healthy female participants with an average age of 33. Their skin type was identified as phototype I/II. They were asked randomly to take 55 grams of olive oil or tomato paste in olive oil for a period of 12 weeks. Skin samples from the 17 women who completed the study showed that lycopene had improved the skin’s resistance to UV rays. The researchers said that the benefits of lycopene can also be acquired by eating foods containing processed tomatoes in equivalent dosage.

Understanding Lycopene

Lycopene is a bright red carotenoid and carotene pigment found in red fruits and vegetables especially tomatoes, except for cherries and strawberries. Other known sources are red carrots, papayas, watermelons. Lycopene in plants, and in other organisms that require the process of photosynthesis in making food, serve as an important substance in biosynthesizing carotenoids to give the plant its pigmentation. In humans, lycopene is not an essential nutrient but it is commonly found in the usual diet. The richest source of lycopene is processed and heat-treated tomato products like tomato paste and tomato ketchup. Preliminary evidence from several studies regarding lycopene’s antioxidant properties has made it one of the candidates as a potential agent in the prevention of cancer.

Sources of Lycopene

Lycopene in food supplements and beauty products is usually extracted from tomatoes but the substance can also be synthesized. Amongst the richest natural source of lycopene are pink guava, wolfberry, seabuckthorn, red bell pepper, gac, papaya and of course, tomatoes. Raw tomatoes contain 9 micrograms of lycopene per 42 grams or weight. Some species of tomatoes can have higher lycopene content than others and it rises as the fruit begins to ripen. Gac is known to have the highest content of lycopene with up to 70 times more than tomatoes, but gac is rarely found outside the regions of Southeast Asia.

Antioxidant Properties of Lycopene

Singlet oxygen is produced during a person’s exposure to UV rays and it is the primary cause of skin aging. Carotenoid quenchers are needed to counteract the adverse effects of singlet oxygen to the body. In studies, lycopene has 125 times more the quenching power than glutathione and 100 times more than vitamin. This makes it one of the most potent antioxidants and also one of the most effective substances against skin aging from a natural source.

Health Benefits of Lycopene

Lycopene is continuously being studied for its efficacy in the prevention of several types of cancer. Studies have shown significant evidence of lycopene’s protective properties against lung cancer, prostate cancer and cancer of the stomach. But results and findings remain preliminary and inconclusive, and further research is required to really determine the efficacy of lycopene as an anti-cancer agent.

Asthma

Though no concrete evidence has been established regarding this matter, lycopene had shown indication from scientific studies of being potent in preventing asthma caused by exercise and heightened physical exertion. This is rooted mainly on lycopene’s antioxidant properties.

Cancer Prevention

Studies done in animals to determine the relationship of developing cancer and regular consumption of lycopene from tomatoes showed indications of reduced risk. But like any other studies regarding lycopene, results are still inconclusive and preliminary. Nevertheless, population and epidemiologic studies on the dietary habits and lifestyle of large populations showed lower risk of developing cancer for people with sufficient fruits and vegetable consumption and adequate exercise than the portion of the population with a sedentary lifestyle. It’s not clear whether lycopene is contributory to the effect, but studies are continuously investigating the matter. Despite all the uncertainties, getting sufficient dosage of lycopene from tomatoes and processed tomato products will not harm you either.

Lycopene for Healthy Skin

Lycopene can be used as a sunscreen and antioxidant in one. Once in the body, lycopene deters skin aging by destroying free radicals and protects the skin from the inside against damage caused by the UV rays of the sun. Lycopene supplements and lycopene skin care products like lycopene lotion with relatively efficient SPF levels are crowding the market. The lycopene content of these products may come from natural sources or they may have been synthesized artificially. But if you want it the natural way and not from a tube, there will always be the ketchup in the cupboard.

Side-effects of Lycopene

Anything taken in excessive dosage can have harmful effects to the body. Though lycopene is a non-toxic substance commonly found in the usual diet, excess in carotenoid intake may produce colorful side-effects – in the literal sense. Reports of excessive lycopene intake include the case of a woman who experienced skin discoloration called lycopenodermia after excessive and prolonged consumption of tomato products and tomato juice. Her blood had high levels of lycopene and her liver and skin had a yellow to orange color. The woman was advised to have a lycopene-free diet and after three weeks her skin regained its normal color.


Sources

nutraingredients.com
enotalone.com
smartskincare.com

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Metformin, a Review

Metformin is a drug that shows up in discussion here every so often. It is thought to be a calorie restriction mimetic, recapitulating some of the metabolic changes caused by the practice of calorie restriction. Its effects on life span in laboratory animals are up for debate and further accumulation of evidence - the results are on balance more promising than the generally dismal situation for resveratrol, but far less evidently beneficial than rapamycin. Like rapamycin, metformin isn't something you'd want to take as though it were candy, even if the regulators stood back to make that possible, as the side effects are not pleasant and potentially serious.

I should note as an aside that while ongoing research into the effects of old-school drugs of this nature is certainly interesting, it doesn't really present a path to significantly enhanced health and longevity. It is a pity that such research continues to receive the lion's share of funding, given that the best case outcome is an increase in our knowledge of human metabolism, not meaningful longevity therapies. Even if the completely beneficial mechanism of action is split out from the drug's actions - as seems to be underway for rapamycin - the end results will still only be a very modest slowing of aging. You could do better by exercising, or practicing calorie restriction.

For the billions in funding poured into these drug investigation programs, there should be a better grail at the end of the road - such as that offered by the SENS vision of rejuvenation biotechnology. Targeted repair of the biological damage of aging is a far, far better strategy than gently slowing the pace of damage accumulation through old-style drug discovery programs. This is a biotechnology revolution: time to start acting like it.

Anyway, aside done, let me point you to a recent open access review on metformin: the interesting work that won't really be in any way relevant to the future of your longevity, but which I'll wager has raised more funding as an object of study than the entire present extant SENS program and directly related scientific studies:

Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan. Gradually accumulating discrepancies about its effect on cancer and obesity can be explained by the shortage of randomized clinical trials, differences between control groups (reference points), gender- and age-associated effects and pharmacogenetic factors. Studies of the potential antiaging effects of antidiabetic biguanides, such as metformin, are still experimental for obvious reasons and their results are currently ambiguous.

...

The wave of interest, with periodical decays and increasing surges, was associated with the attempts to use antidiabetic biguanides [such as metformin] to control body weight and tumor growth. Another facet of the situation is that almost 45 years ago these drugs were suggested to promote longevity. Over the last years, the expanding bodies of relevant evidence, which mainly related to metformin, started to merge and occupy increasing place in current literature. The objective of the present essay is to attract more attention to accumulating inconsistencies. The first two sections of the essay, which are related to obesity and cancer, are based mostly on clinical data. The third section, which is related to aging or, rather, antiaging, is based predominately on experimental evidence obtained in rodents. Clearly, obesity and cancer have numerous interrelationships with aging, [however], we will separate these aspects for the sake of clarity in discussing the relevant effects of metformin.

See what you think; it makes for an interesting read - and includes a table of results from a number of life span studies that are, indeed, all over the map. It somewhat reinforces the point that unambiguous success in extending healthy life is not going to arrive from this quarter. Think SENS, not drug discovery - what will come from the drug discovery clade is a slow, grinding, and expensive cataloging of the fine details of genetics, metabolism, and aging in mammals.

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

Work on Restoring Function in Huntington's Disease

Researchers "have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models. ... Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD. ... the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed. ... transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD."

Link: http://www.vai.org/News/News/2012/05_29_Huntingtons.aspx

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

Resveratrol and the Big Red Lever, Revisited

Back in 2006 I had this to say on the topic of what was then the first flush of popular interest in resveratrol, back when far less was known about it:

Our metabolic biochemistry looks like a big wall full of levers. Some of them are painted red, and we think we understand what the instructions beneath these red levers say. Maybe. How much information do you feel you would like before you pull the big red levers in your own personal metabolism? What level of risk due to disease would you presently need to be suffering in order to take the risk represented by a new compound? How do you evaluate these levels of risk?

Resveratrol has turned out, almost predictably, to be another heaped mound of hype that buries a modest kernel of interesting-but-not-terribly-applicable metabolic research. At this stage it seems fairly certain that resveratrol does not extend life in mammals to any great degree - when you find compounds that can do that, there is little uncertainty once the life span studies are in and replicated. See the past couple of years of work on rapamycin in mice as a contrasting example to the uncertainty and lack of verifiable effects for resveratrol and its derived compounds.

In any case, I was reminded of the topic by a recent post at In the Pipeline that echoes many of the same sentiments in my 2006 post:

I've written many times here about sirtuins, and their most famous associated small molecule, resveratrol. And I've been asked more than once by people outside the med-chem field if I take (or would take) resveratrol, given the available evidence. My reply has been the same for several years: no, not yet. Why so cautious, for a compound that's found in red grapes and other foods, and to which I've presumably been exposed many times? Several reasons - I'll lay them out and let readers decide how valid they are and how they'd weight these factors themselves.

...

So what do we know about what resveratrol does? A lot, and not nearly enough. Its pharmacology is very complex indeed, and the one thing that you can clearly draw from the (large) scientific literature is that its (a) a very biochemically active compound and (b) we haven't figured out many of those actions yet. Not even close. Even if all it did was act as on one or more sirtuins, that would be enough to tell us that we didn't understand it.

...

There's room to wonder about the mechanisms of a number of drugs. Indeed, there have been many that have made it to market (and stayed there for many years) without anyone knowing their mechanisms at all. We're still finding things out about aspirin; how much can one expect? Well, one response to that is that aspirin has been used widely in the human population for quite a long time now, and resveratrol hasn't. So the question is, what do we know about what resveratrol actually does in living creatures? If it has beneficial effects, why not go ahead and take advantage of them?

Unfortunately, the situation is wildly confusing (for an overview, see here). The first thing that brought resveratrol into the spotlight was life extension in animal models, so you'd think that that would be well worked out by now, but boy, would you be wrong. The confusion extends up to mouse models, where some of the conclusions - all from respectable groups in respectable publications - seem to flatly contradict each other. No, the animal-model work on resveratrol is such a bubbling swamp that I don't see how anyone can safely draw conclusions from it.

We can conclude that it doesn't straightforwardly extend life at this point. So you have on the one hand a distinct lack of knowledge as to long term effects and on the other hand it clearly isn't doing anything spectacular in laboratory animals. That looks like the worst of both worlds from where I stand.

The sensible thing to do whenever another of these oral-fixation ingested substance hype machines emerges from the juncture of the scientific and business worlds is to balance the purported results against the clear, proven, and solid benefits of exercise and calorie restriction. The risks in moderate exercise and calorie restriction are minimal, while the evidence for great benefit to long-term health is gold-plated and voluminous. When someone is trying to convince you to spend money on something that seems unlikely to produce even a pale shadow of the health benefits of either exercise or calorie restriction, and has largely unknown long term risks - then why even try? It just doesn't make sense.

The research community, and just as importantly the public at large, needs to move beyond their enthusiasm for metabolic manipulation through ingested substances as a path to extending healthy life. It's a grand example of looking for the lost keys under the lamp post - doing something just because it's easier and the path of least resistance, regardless of the likelihood of significant results at the end of the day. Real progress towards longer lives is only going to come through building medical technology capable of repair and rejuvenation at the level cells, organs, and systems within the body: very specific biotechnologies engineered to perform very specific jobs within and around cell structures, and aim to exactly reverse aging by doing so. That couldn't possibly be further removed from the present dominant strategy of mining the natural world for compounds that might or might not cause more minor benefits than minor disadvantages.

It's a common refrain here, but no less true for it: work on rejuvenation biotechnology must displace the present longevity science mainstream if we want to see significant progress towards radical life extension occur before we run out of time, aged to death on the very verge of success.

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

An Update on Comparative Studies of Longevity

Researchers are comparing the biochemistry of long-lived species to better understand the roots of large differences in life span: "The team looked at the genome of more than 30 mammalian species to identify proteins that evolve in connection with the longevity of a species. They found that a protein, important in responding to DNA damage, evolves and mutates in a non-random way in species that are longer-lived, suggesting that it is changing for a specific purpose. They found a similar pattern in proteins associated with metabolism, cholesterol and pathways involved in the recycling of proteins. Findings show that if certain proteins are being selected by evolution to change in long-lived mammals like humans and elephants, then it is possible that these species have optimized pathways that repair molecular damage, compared to shorter-lived animals, such as mice. ... The genetic basis for longevity differences between species remains a major puzzle of biology. A mouse lives less than five years and yet humans can live to over 100 for example. If we can identify the proteins that allow some species to live longer than others we could use this knowledge to improve human health and slow the aging process."

Link: http://esciencenews.com/articles/2012/03/29/study.suggests.why.some.animals.live.longer

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

Explaining How Altered IGF-1 Signaling Extends Life

Signs of progress in understanding the mechanisms of induced longevity through altered insulin/IGF-1 signaling are shown in this paper. This is one of the most-studied class of longevity mutations in lower animals, despite there being some debate over whether it is relevant to mammal biochemistry. Here, the basic mechanism is explained as being hormetic, centering on the mitochondria: researchers "elucidate a conserved mechanism through which reduced insulin-IGF1 signaling activates an AMP-kinase-driven metabolic shift toward oxidative proline metabolism. This, in turn, produces an adaptive mitochondrial [reactive oxygen species (ROS)] signal that extends worm life span. These findings further bolster the concept of mitohormesis as a critical component of conserved aging and longevity pathways. ... Impaired insulin and IGF-1 signaling (iIIS) in C. elegans daf-2 mutants extends life span more than 2-fold. Constitutively, iIIS increases mitochondrial activity and reduces reactive oxygen species (ROS) levels. By contrast, acute impairment of daf-2 in adult C. elegans reduces glucose uptake and transiently increases ROS. Consistent with the concept of mitohormesis, this ROS signal causes an adaptive response by inducing ROS defense enzymes, culminating in ultimately reduced ROS levels despite increased mitochondrial activity. Inhibition of this ROS signal by antioxidants reduces iIIS-mediated longevity by up to 60%. ... IIIS upregulates mitochondrial L-proline catabolism, and impairment of the latter impairs the life span-extending capacity of iIIS while L-proline supplementation extends C. elegans life span. Taken together, iIIS promotes L-proline metabolism to generate a ROS signal for the adaptive induction of endogenous stress defense to extend life span."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22482728

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

"Yet Another Useless Lifestyle Study"

I am not unsympathetic to this viewpoint: recent research shows that "women should raise their glasses to a healthier old age, but we've heard it all before - and just the opposite. ... This is the conclusion of a study of 14,000 female nurses that started in 1976. The brainchild of the Harvard School of Public Health, Boston is the latest result from numerous studies of this nature that have produced all manner of contradictory results. ... In 1976, the [Framington study] is supposed to have shown a connection between menopause and the increased risk of heart disease, which is a bit like saying it found a connection between age and life expectancy - exactly what is one supposed to do with a datum like that? ... At the end of the day, one must ask what is the point of such studies, and specifically what is the point of a study that attempts to link the consumption of wine by women with longevity, especially when Marie Lloyd was telling us a little of what you fancy does you good way back in 1915? Rather than mounting expensive years' or decades' long studies as make-work schemes for medical scientists and their chums in Whitehall, Washington and elsewhere, the governments of the world might be better advised setting them to work to discover the actual causes of disease, and maybe to develop vaccines and other methods of combatting them, or better still, maybe they should follow in the footsteps of gerontologist Aubrey de Grey and his SENS organisation?"

Link: http://www.digitaljournal.com/article/311235

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

Building Insulin-Producing Pancreatic Cell Clusters

Progress in the tissue engineering of cell structures for use as research tools, and later as the basis for therapies: "Three-dimensional clusters of pancreatic beta-cells that live much longer and secrete more insulin than single cells grown in the laboratory are valuable new tools for studying pancreatic diseases such as diabetes and for testing novel therapies. This cutting-edge advance is described in [an open access paper] ... Finding a solution for the culturing and final transplantation of pancreatic cells will be an enormous breakthrough for the treatment of diabetes ... Growing pancreatic cells in the laboratory is challenging, in part because to survive and function normally they require cell-cell contact. [Researchers] developed an innovative method that uses photolithography to create microwell cell culture environments that support the formation of 3-D pancreatic beta-cell clusters and control the size of the cell aggregates. They describe the ability to remove these cell clusters from the microwells and encapsulate them in hydrogels for subsequent testing or implantation."

Link: http://www.sciencecodex.com/new_method_yields_insulinproducing_pancreatic_cell_clusters-89204

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

Training the Immune System to Destroy Cancer

The New York Times is running a piece on a recent small trial of immune therapy for leukemia: "A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose. Doctors removed a billion of his T-cells - a type of white blood cell that fights viruses and tumors - and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig's veins. At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst. A few weeks later, the fevers were gone. And so was the leukemia. There was no trace of it anywhere - no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells. A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work."

Link: http://www.nytimes.com/2011/09/13/health/13gene.html?pagewanted=all

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