Proposing Concurrent Manipulation of Multiple Metabolic Pathways

That part of the research community focused on manipulating metabolism to slow down aging has advanced to the point of considering multiple distinct simultaneous changes to achieve the desired end result: "Modern medicine is directed towards the prevention, detection and cure of individual diseases. Yet, current medical models inadequately describe aging-associated diseases. We now know that failure in longevity pathways including oxidative stress, multisystem dysregulation, inflammation, sarcopenia, protein deposition and atherosclerosis are associated with age-related diseases. Such longevity pathways are potential targets for therapeutic intervention. Interventions in specific pathways have been shown to ameliorate and postpone the aging phenotype by activation of multiple genes. The strategy that we propose in this paper is to apply interventions simultaneously on complementary longevity pathways to achieve a synergistic result. For instance, aging is known to attenuate the HSF1 pathway leading to production of very toxic beta-amyloid fibrils. Consequently, the FoxO pathway is activated, resulting in the formation of less toxic high molecular weight aggregates as a defense mechanism. Thus the simultaneous upregulation of the HSF1 and FoxO pathways could potentially decrease protein deposition and proteotoxicity, thereby retarding or possibly preventing the onset of neurodegenerative diseases. Modulating these two pathways may also delay the onset of other age-related pathologies including cognitive decline, cancer, diabetes and cardiovascular disease due to its multi-gene effect. "

Link: http://www.ncbi.nlm.nih.gov/pubmed/21834787

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

You Pays Your Money, You Takes Your Chances

What happens across your lifetime to change you from young to old is known as stochastic damage - the integrity of your bodily systems nibbled away, one damaged or misplaced clump of atoms at a time. At the detail level of molecular machinery, this is basically random. But the process is statistically predictable when you start to look at the bigger picture: our bodies are all, sadly, headed downhill in much the same general direction, and we can even talk about trends, environmental factors, and speeds of decline when we examine large groups of people.

For you, personally, what this means is that you have a ticket to ride and you can steer the bounds of the possible by your actions. But there's no such thing as absolute control - there are only risks to be shifted one way or another. Laze around and grow fat, and watch the risk of diabetes, cancer, and dementia grow much larger. Or smoke and suffer the likely consequences. Or avoid doctors like the plague for two dozen years and you're making your own bad luck, slowly but surely.

Some people sail through all that exactly because they were lucky, or both lucky and possessed of rare protective genes. Equally, you could do everything right, live the healthiest life possible, and get nailed by cancer in your twenties, or by the sudden onset of an unsuspected genetic condition in your thirties, or by an autoimmune disease despite no history of it in your family. Or, hell, by some idiot operating heavy machinery without a license while you're minding your own business on the sidewalk. These things happen. They're rare, but the point is that they're on the ticket: all you can do is swing the odds.

Some people die young and despite living well: it happens. I'm sure we can all think of a few we've known. But that doesn't remove any of the value of living well, doing the right things for your health, and generally trying to keep on the right side of heavy machinery. It's a matter of odds. Too many people look at disease in later life as exclusively bad luck, whereas they in fact had a hand in moving the needle the wrong way:

Lifetime physical inactivity interacts with secondary aging (i.e., aging caused by diseases and environmental factors) in three patterns of response. First, lifetime physical inactivity confers no apparent effects on a given set of physiological functions. Second, lifetime physical inactivity accelerates secondary aging (e.g., speeding the reduction in bone mineral density, maximal oxygen consumption, and skeletal muscle strength and power), but does not alter the primary aging of these systems. Third, a lifetime of physical activity to the age of ~60-70 years old totally prevents decrements in some age-associated risk factors for major chronic diseases, such as endothelial dysfunction and insulin resistance. The present review provides ample and compelling evidence that physical inactivity has a large impact in shortening average life expectancy. In summary, physical inactivity plays a major role in the secondary aging of many essential physiological functions, and this aging can be prevented through a lifetime of physical activity.

In some things we can make our own luck; in others we can't. Not much that can be done today about the bolt from the blue cancer in your teens, or the genetics that dealt you a heart that'll have to be nursed like the engine in a second hand car for the rest of your life. But for the rest of it: the prepared and the foresighted have what looks like great luck in life - at least from the perspective of people who didn't pay attention to all the groundwork that led to that point.

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

Induced Pluripotent Stem Cells Versus Liver Damage

More signs of progress in regenerative medicine: "researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage. ... liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue. ... iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells. ... Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability ... Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory."

Link: http://www.eurekalert.org/pub_releases/2011-05/jhmi-asc051011.php

Another Possible Avenue to Partial Rejuvenation of the Aged Immune System

The aged immune system begins to fail at its job for a variety of reasons that seem to have more to do with its evolved structure and control systems than with the outright incapacity of immune cells, or the inability to generate more immune cells. The immune system evolved to work very effectively in younger life, and that comes at the cost of controlling processes that fall down badly in the long term.

A small reserve of memory cells is needed to respond effectively to previously encountered threats - one reserve per threat. The more threats you have encountered, the more cells become devoted to memory; eventually you don't have enough naive T cells left to mount any sort of effective defense.

Given the capabilities that remain in the body, an aged immune system could, in theory, get up to fight and fight well - but it doesn't. That shortcoming may be addressed by selectively manipulating the system and its cells, however. For example, in recent years researchers have demonstrated that we can (a) intervene via modern medicine to expand the population of useful immune cells, or (b) destroy the accumulation of useless immune cells and thereby immediately free up space so that the body creates more useful immune cells, or even (c) wipe out and recreate the entire immune system as a fresh start, which works to cure autoimmune diseases in which immune cells run amok and attack the body.

I noticed a research release today that discusses the identification of another potential source of useful cells in the aged immune system, cells normally left inactive thanks to the evolved control systems that focus on early life at the expense of later life. The researchers show that these cells can be activated for duty:

Professor Arne Akbar of UCL (University College London), who led this research, explains "Our immune systems get progressively weaker as we age because each time we recover from an infection a proportion of our white blood cells become deactivated. This is an important process that has probably evolved to prevent certain cancers, but as the proportion of inactive cells builds up over time our defences become weakened. What this research shows is that some of these cells are being actively switched off in our bodies by a mechanism which hadn't been identified before as important in ageing in the immune system. Whilst we wouldn't want to reactivate these cells permanently, we have an idea now of how to wake them from their slumber temporarily, just to give the immune system a little boost."

...

When the researchers blocked this newly identified pathway in the lab they found that the white blood cells appeared to be reactivated. Medicines which block this pathway are already being developed and tested for use in other treatments so the next step in this research is to explore further whether white blood cells could be reactivated in older people, and what benefits this could bring.

I see it as a good sign that there are a range of different potential lines of research that might lead to varying degrees of immune system rejuvenation, temporary or otherwise. Variety and competition are signs of a healthy field of medicine.

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

The Cost of Inactivity

Researchers find what looks to be a proxy measure for the degree to which a person is sedentary - but of course there might be other important correlations here, such as with wealth or intelligence: "Watching TV for an average of six hours a day could shorten the viewer's life expectancy by almost five years ...The impact rivals that of other well known behavioural risk factors, such as smoking and lack of exercise, the study suggests. Sedentary behaviour - as distinct from too little exercise - is associated with a higher risk of death, particularly from heart attack or stroke. Watching TV accounts for a substantial amount of sedentary activity, but its impact on life expectancy has not been assessed, say the authors. They used previously published data on the relationship between TV viewing time and death from analyses of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), as well as Australian national population and mortality figures for 2008, to construct a lifetime risk framework. AusDiab is a national survey of a representative sample of the population, starting in 1999-2000, and involving more than 11,000 adults aged 25 or older. The authors then constructed a risk framework for the Australian population in 2008, based on the answers the survey participants had given, when quizzed about the total amount of time they had spent in the previous week watching TV or videos. ... These figures compare with the impact of other well known lifestyle factors on the risk of death from cardiovascular disease after the age of 50, including physical activity and obesity. For example, other research has shown that lifelong smoking is associated with the shortening of life expectancy by more than 4 years after the age of 50, with the average loss of life from one cigarette calculated to be 11 minutes - equivalent to half an hour of TV watching, according to the authors' risk framework." I applaud the researchers for finding a way to present their work that will likely get a lot of play in the media.

Link: http://www.eurekalert.org/pub_releases/2011-08/bmj-dtq081511.php

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

Muddy Waters When it Comes to Quahog Biochemistry and Longevity

Yes, we're back to clams again: four hundred year old clams in this case. The ocean quahog, Arctica islandica, is a very long-lived bivalve that, like other unusually long-lived species, is attracting the attention of researchers. How is it that these animals manage to live so much longer than their near relatives? You'll find some background reading in the archives:

Researchers to date have focused on resistance to oxidative damage in quahogs, but the more research is done, the more ambiguous that picture becomes. It doesn't seem to be the case that we can simply point to very high levels of antioxidants or an aggressive antioxidant response that preserves cells from the accumulating damage caused by oxidative byproducts of metabolism. In many ways this parallels research into the biochemistry of the naked mole-rat: the initial focus on examining natural antioxidants gave way to the present view that their comparatively long life span depends on differences in the construction of their vulnerable cell membranes. They are better built in the places where it matters - their cells are buzzing with reactive oxidant compounds, but their resistant cell membranes shrug it off.

That may be the case for the quahog as well, but researchers aren't there yet. This recent paper manages to continue the present trend of muddying the waters:

We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage elimination processes in long-lived A islandica with the shorter-lived hard clam, Mercenaria mercenaria. We compared baseline biochemical profiles, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP).

Our data support the premise that extreme longevity in A islandica is associated with an attenuated cellular reactive oxygen species production. The observation of reduced protein carbonyl concentration in A islandica gill tissue compared with M mercenaria suggests that reduced reactive oxygen species production in long-living bivalves is associated with lower levels of accumulated macromolecular damage, suggesting cellular redox homeostasis may determine life span. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level.

Following TBHP exposure, we observed not only an association between longevity and resistance to oxidative stress-induced mortality but also marked resistance to oxidative stress-induced cell death in the longer-living bivalves. Contrary to some expectations from the oxidative stress hypothesis, we observed that A islandica exhibited neither greater antioxidant capacities nor specific activities than in M mercenaria nor a more pronounced homeostatic antioxidant response following TBHP exposure. The study also failed to provide support for the exceptional longevity of A islandica being associated with enhanced protein recycling.

Which is really saying little that is new and definitive - just better ruling out some of the options. The quahog could be producing fewer oxidants, or it could be efficiently mopping up oxidants at their source in the mitochondria due to a natural source of localized antioxidant compounds. In either case, that says nothing about how it or its cells might react to an externally provided and artificial source of oxidative stress like TBHP. Given the present pace of work, however, I'd expect that researchers will have developed a well-supported consensus explanation for the extreme longevity of this species and the naked-mole rat by the time 2020 rolls around.

Complicating the Picture for Calorie Restriction and Fat

A survey of calorie restriction in many mouse breeds finds that it doesn't work to extend healthy life in all, and that difference appears to be related to the degree to which calorie restriction results in fat loss. This presents an interesting complication, given that it has been clearly demonstrated that surgically removing visceral fat extends life in mice, and the human studies of calorie restriction show unambiguously positive results on health: "Since the 1930s scientists have proposed food restriction as a way to extend life in mice. Though feeding a reduced-calorie diet has indeed lengthened the life spans of mice, rats and many other species, new studies with dozens of different mouse strains indicate that food restriction does not work in all cases. ... [Researchers] studied the effect of food restriction on fat and weight loss in 41 genetically different strains of mice. The scientists then correlated the amount of fat reduction to life span. The answer: Mice that maintained their fat actually lived longer. Those that lost fat died earlier. ... Indeed, the greater the fat loss, the greater the likelihood the mice would have a negative response to dietary restriction, i.e., shortened life. This is contrary to the widely held view that loss of fat is important for the life-extending effect of dietary restriction. It turns the tables a bit."

Link: http://www.mysanantonio.com/news/article/UT-mouse-study-suggests-cutting-calories-may-not-1365206.php

Stem Cell Clinical Trials in India

From the Telegraph: "India's first set of government-approved clinical trials of stem cells on patients with chronic obstructive lung disease, diabetes, liver cirrhosis and osteoarthritis are likely to begin in five cities in April this year. A Bangalore-based company, Stempeutics Research, has received approval from the country's drug regulatory agency to evaluate the efficacy of its stem cells on these four incurable diseases after safety assessments over the past year on patients with cardiovascular disease. The efficacy - Phase II - trials are likely to begin on small groups of volunteer patients offered the experimental treatment in collaborating hospitals in Bangalore, Kochi, Delhi, Mangalore and Manipal, a senior Stempeutics official said. Each volunteer patient will receive a dose of mesenchymal stem cells derived from the bone marrow of healthy persons. The stem cells, coaxed to proliferate in a broth of laboratory biochemicals, will be injected at the site of illness - the pancreas, the liver, the lungs, or the bone - where they are expected to stimulate resident stem cells and regenerate the damaged or lost tissue. While private and even government hospitals have in the past offered stem cell therapy to patients with intractable conditions, the proposal by Stempeutics is the first with formal approval from regulators for chronic obstructive pulmonary disease (COPD), diabetes, liver cirrhosis and osteoarthritis."

Link: http://www.telegraphindia.com/1110216/jsp/frontpage/story_13589821.jsp

Exercise Versus Accelerated Mitochondrial Dysfunction

Researchers demonstrate that exercise can counter some of the effects of an engineered acceleration of mitochondrial dysfunction: "researchers [found] that signs of premature aging were halted - and even reversed - in virtually every tissue and organ in the bodies of exercised mice. Mice genetically altered to age faster were forced to run on treadmills for 45 minutes, three times a week. Five months later, the mice looked as young, healthy and active as wild-type mice - mice that didn't have the genetic mutation - while their sedentary and same-aged siblings were balding, greying and shrinking. .. The mice were genetically manipulated to age twice as fast as normal because of a defect in the repair system of their mitochondria, the powerhouses or furnaces inside each cell that give our body energy. Evidence has been mounting for decades that the older we get, the more mutations we accumulate in mitochondrial DNA. The furnaces start to break down, resulting in a steady decline in tissue and organ function. ... In our study, we saw huge recovery in mitochondrial function [in] the exercised mice." We might expect this result, given that exercise is known to have an impact on longevity, as well as on many of the biological mechanisms that are associated with aging. Given the importance of mitochondria in aging, it is interesting to see more work on the links between exercise and their function - but we must always be careful when evaluating work based on engineered dysfunction or accelerated aging. It is often the case that the putative end result has little relevance to "normal" aging.

Link: http://www.vancouversun.com/health/health/4321105/story.html

Aging, Inflammation, and Osteoarthritis

Low-level chronic inflammation is produced by the aging immune system and causes many further problems: "Osteoarthritis (OA) is the most common cause of chronic disability in older adults. Although classically considered a 'wear and tear' degenerative condition of articular joints, recent studies have demonstrated an inflammatory component to OA that includes increased activity of several cytokines and chemokines in joint tissues that drive production of matrix-degrading enzymes. Rather than directly causing OA, aging changes in the musculoskeletal system contribute to the development of OA by making the joint more susceptible to the effects of other OA risk factors that include abnormal biomechanics, joint injury, genetics, and obesity. Age-related sarcopenia and increased bone turnover may also contribute to the development of OA. Understanding the basic mechanisms by which aging affects joint tissues should provide new targets for slowing or preventing the development of OA."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20699160

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

Editorial: Reasons for optimism on the eve of a new decade – Times Colonist

A century ago, the world stood at the brink of the Roaring Twenties, a decade of exuberance, prosperity and growth. Will 2020 usher in a similar era? There are reasons to believe so, though the scales are more finely balanced.

In the closing days of 1919, the ravages of war were slowly receding. For years, the great powers had been totally absorbed in the pursuit of death and destruction. Now they could move forward to rebuild and expand.

No such liberation stands in the offing as we enter the decade ahead. Canada's economy, having weathered the recession of 2007-08, is stable, yet challenges abound.

The most potent political issue of the day, global warming, makes for an uncertain future. There is no consensus about how to balance action on this front, with the urgent need for additional revenues to reinforce our safety net programs.

We have a minority government in Ottawa, whose longevity is uncertain.

Britain is leaving the European Union, at a price that remains to be seen.

And south of the border, Donald Trump has been impeached, while the 2020 presidential election campaign looks likely to be the nastiest in recent times.

In short, the path ahead is unclear.

Still, there are reasons for optimism. The differences that divide us are far fewer than the ties that bind us.

Quebec nationalism has subsided.

Anger in Alberta that the West is ignored will simmer for a time, but we have typical Canadian ways of addressing such conflicts through compromise and civility.

Abroad, the lessons of the 20th century have largely been learned. Armed conflict settles nothing, and no-one gains from trade disputes, as the United States is learning.

The unprecedented access of people around the globe to information via the internet is creating new generations with broader horizons and immensely improved access to learning.

As a result, our world is safer and saner than at any time in history.

In medical science, the long-awaited rewards of decoding the genome are finally beginning to appear. Promising new treatments for Alzheimers disease and cystic fibrosis are in sight.

Yes, these drugs still have some way to go before their full potential is realized. But the pace is gathering by the year.

Virtual medicine, where specialists at distant locations can diagnose disease and suggest treatment, is already with us. Robots are aiding precision in surgery.

In the workplace, smart machines will increasingly free humans from long hours of unsafe and repetitive tasks. Some have worried this may make human labour redundant, but that seems unlikely.

The Industrial Revolution created more jobs than it destroyed, and artificial intelligence may do the same. The decade ahead will revolutionize the work site.

Globally, altruism and enlightenment are slowly extinguishing famine and plagues. A century ago, the majority of the worlds population lived in poverty. Average life expectancy was 35.

Today only 10 per cent struggle below the poverty line, and life expectancy has more than doubled. These improvements will continue in the years to come.

AIDS, once invariably deadly, has been tamed, smallpox has been eradicated, and it is possible that polio may be all but wiped out by 2030.

These gains were made possible, in large part, by a growing commitment to international co-operation, unthinkable a century ago.

In short, the better instincts of humankind, in the pasttoo often overshadowed by our faults, are slowly prevailing.

True, we are an aging society, and that poses challenges of its own. Yet our younger generation is more socially active, more progressive and more self-confident than ever.

There is reason to believe these trends will persist in 2020 and beyond, ensuring the long arc of history continues its steady curve toward betterment.

That, at any rate, is our hope as we prepare to welcome a new decade.

Follow this link:
Editorial: Reasons for optimism on the eve of a new decade - Times Colonist

Vaccinating Against Atherosclerosis

An interesting example of how immune therapies can eliminate or reduce some of the ways in which the aging body damages itself: "Cholesterol is transported in the blood in LDL particles, which are a kind of fat drops that can accumulate in the walls of blood vessels. LDL activates the immune defence and triggers an inflammation in the blood vessels that leads to atherosclerosis (also known as arteriosclerosis). When the atherosclerotic plaque finally ruptures, a blood clot is formed that in turn can cause a heart attack or stroke. It was previously thought that the inflammation in the blood vessels arises when the T cells react to oxidised LDL particles located in the atherosclerotic plaque. Now, however, [researchers have found] that the opposite is true, namely that the T cells react to components in the normal LDL particles, and that they no longer recognise LDL once it has been oxidised. ... Since reactions to LDL can be dangerous, T cells are normally held in check by inhibitory signals. The body's own control works well as long as the LDL keeps to the blood, liver and lymph glands. But when it accumulates in the artery wall, this inhibition is no longer enough, the T cells are activated and an inflammation arises. ... Vaccination against the receptor that the T cells use to recognise LDL can block the immune reaction and reduce the disease by between 60 and 70 per cent."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/ki-nav050610.php

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

Study Identifies Link Between Smoking and Urinary Health

Smoking cessation plus exercise can improve the male sexual function and also improve the urinary health of both males and females.

In a recently concluded study presented in the annual conference of the American Urological Association, researchers pointed to a vital link between smoking, exercise and urinary health.

The study involved two thousand individuals (males and females). The respondents were interviewed about their smoking habits and were also given questions regarding their urinary health.  It was found that individuals who smoked were three times more likely to urinate frequently.

Also, these individuals are also 2.7 times more prone to experience sudden urges to go to the bathroom to urinate.

In a related study performed by US researchers from South Carolina, it was found that men who exercised more had experienced improved sexual function.  The two studies, if taken together, point to an age-old medical adage: folks have to stop the smoking habit and begin a healthier habit – exercise!

More reasons to love exercise

Here are even more reasons to love exercise:

1. Exercise reduces the risk of mortality from chornic, degenerative health conditions.

2. Exercise reduces the chance of developing of type 2 or insulin-dependent diabetes.

3. Exercise can help control the blood pressure, even the blood pressure of people already have cardiovascular problems.

4. Exercise can help reduce the probability of developing one of the top killers worldwide: colon cancer.

5. Exercise helps improve your mood and also helps people ease out of anxiety and depression.

6. Exercise improves balance, coordination and also strengthens the bones and muscles, therey reducing the risk of fractures from falls.

7. Exercise is also an excellent means of losing weight.

8. Exercise make the body and mind more fit. If you are physically and mentally fit, you would be able to perform better at work or in school.

9. Exercise reduces the risk of stroke.

Exercise may also reduce the risk of breast cancer and loss of bone mass (osteoporosis) – two common problems of women over the age of 45.

Sources:
aolhealth.com
nutristrategy.com
www2.gsu.edu
medicinenet.com

Discuss this article in Frank Mangano’s forum!

Fully Functional Hair Regeneration Demonstrated

Researchers have been manipulating stem cells to cause hair follicles to form and hair to grow for a few years now. Consider this research from 2009, for example:

Professor Lin Sung-jan took 10 hair follicles from rodents and cultivated 8 to 10 million dermal papilla cells in vitro in 20 days. Using aggregates of between 3 and 5 million dermal papilla cells, he mixed these with rodent skin cells and transplanted them onto bare rodent skin, which sprouted hair.

Bald skin and haired skin have the same cell populations needed to grow hair, as it turns out, so this sort of cell-based approach has merit. The end of the story will likely be some form of cell signalling treatment to instruct cells already present in the body to form hairs in an area of skin rather than cell transplants - but transplants are first in line for development. The process is not exactly straightforward, unfortunately. Much like the tissue engineering of teeth, some form of guiding technology must be established to ensure that the cells grow as they should - without it, you end up with misshapen or broken structures.

On this subject, the work of a Japanese group on hair regeneration has been in the news of late, and they seem to have established a proof of principle for guiding correct hair growth. You'll find an open access paper and a couple of popular press items to choose from, complete with pictures of a hairless mouse sporting a patch of engineered hair:

Previously, Tsuji and colleagues had bioengineered follicles and hair shafts in the lab using epithelial and mesenchymal cells from mouse embryos. Until now, it was unclear whether these organized clusters of cells would make normal hair if inserted into mouse skin.

In the new work, the team transplanted a group of the engineered follicles into the skin on the backs of hairless mice. After about two weeks, hairs began to sprout. Under the microscope, the hair grown from the bioengineered mouse follicles resembled normal hair, scientists found. And the mouse follicles went through the normal cycle of growing hair, shedding and making new hair.

When researchers injected the region around the bioengineered follicle with acetylcholine, a drug that causes muscles to contract, the hairs perked up. This suggests that the transplanted follicles had integrated with surrounding muscle and nerves like normal hair follicles do.

Importantly, the researchers were able to ensure hair didn't become ingrown or point in the wrong direction by attaching a nylon thread to the engineered follicles and guiding the hair to grow outward.

That guide method doesn't sound very scalable - though given that there is a market for hair restoration techniques that involve moving follicles one by one, I could see it finding use in the clinic. But we can live without our hair and our vanity; a legion of far more serious and life-threatening degenerations accompany aging, and those are where our attention should be directed. The most important long-term effects of this particular line of research will, I think, be the application of the lessons learned to other areas of tissue engineering: guiding the regeneration of small complex structures, of which there are a great many in the body.

The results also mark a step forward in efforts to regenerate organs such as salivary glands that form in a process similar to hair early in their development.

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

Longevity Genes Project | Institute for Aging Research …

Nir Barzilai, M.D. Director of the Institute for Aging

Research Director of the Nathan Shock Center of Excellence in the Basic Biology of Aging

Ingeborg and Ira Leon Rennert Chair of Aging Research

Dr. Barzilai's bio / cv

Watch video

Request an Interview with Dr. Barzilai

Watch Dr. Barzilai in The Healthspan Imperative

The Longevity Genes Project

What if people could live to be 100 and beyond and still be healthy, active and engaged?

What if there were a way to age without a slow and painful decline?

In the Longevity Genes Project at Albert Einstein College of Medicine, Dr. Nir Barzilai and his team conducted genetic research on more than 500 healthy elderly people between the ages of 95 and 112 and on their children.

The identification of longevity genes by Einstein researchers could lead to new drug therapies that might help people live longer, healthier lives and avoid or significantly delay age-related diseases such as Alzheimer's disease, type 2 diabetes and cardiovascular disease.

The Longevity Genes Project Video Series

This video series includes informative interviews with Dr. Nir Barzilai, who leads the Einstein longevity research efforts, and with four study participants whose diverse and compelling stories will inspire you. We invite you to view all of the videos and leave comments. Click on the links below to view each segment.

Research: Dr. Nir Barzilai

Personal Profiles: Lilly Port: Age 96 | Harold Laufman: Age 98 | Irma Daniel: Age 103 | Irving Kahn: Age 104

Longevity and Longenity Information and preliminary results of Einstein's search for longevity genes in the Jewish Ashkenazi population and genotypes and phenotypes for exceptional longevity.

Why Ashkenazi Jews? Information about the "founder effect" and the historically unique Ashkenazi Jewish population.

Read more:
Longevity Genes Project | Institute for Aging Research ...

A Reminder that Genetic Contributions to Longevity are Complex

Researchers are turning up a great many human genetic variants associated with natural differences in longevity - a complex, patchwork array of them, each contributing a small amount to the whole: "Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-?) genes may influence human life-expectancy. ... SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes ... Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males ... a significant two-loci interaction occurs in females between ADA 22G>A and TNF-? -238G>A ... both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-? genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21865054

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

An Interesting Issue of Life Extension Magazine

The latest issue of Life Extension Magazine is fairly focused on the long view, and taken as a whole is a more than usually explicit call for the defeat of aging through research and development of the appropriate biotechnology. It is my sense that the mouthpiece of that organization has been steering more towards that direction in recent years, and I'm pleased to see it - the less the LEF folk conduct themselves as a standard issue supplement shop and the more they conduct themselves as a source of advocacy and funding for serious longevity research such as SENS the better they look to my eyes.

There are a couple of articles worth thinking on, starting with one penned by Aubrey de Grey subject that I've held forth on in the past.

Why Aren't More Wealthy People Funding Aging Research?

Since aging is indisputably humanity's worst medical problem, with the treatment (albeit only minimally effective) of age-related diseases consuming the vast majority of the industrialized world's medical budget, one would imagine that all reasonable approaches to the development of medicine to postpone it would be vigorously pursued and well funded. Unfortunately, none of them are. Neither the retardation of aging nor its repair receives a fraction of the research budget - whether from the public purse or from the for-profit biotech sector - that is enjoyed by disease-specific research. And this is despite the fact that gerontologists have been pointing out for decades that even modest progress in the implementation of "preventative geriatrics" - which is exactly what treatment for aging would be - would be staggeringly cost-effective. I believe that the overwhelming reason why politicians (and, to a lesser extent, companies) have not heard this message is not because they fail to understand it but because they dispute the premise. There is a profoundly deep-seated belief that aging is untreatable.

The Ellison Medical Foundation

The Ellison Medical Foundation is the largest private funder of research on aging and the second largest overall funder - second only to the federal government's National Institute on Aging. Since its inception in 1998, Ellison's Medical Foundation has
provided more than $300 million to fund basic biomedical research on aging relevant to understanding life span development processes and age-related diseases and disabilities, including stem cells, telomeres, longevity genes, DNA and mitochondrial damage, Werner Syndrome, Alzheimer's disease, neural development, degeneration and cognitive decline, and cellular response systems to aging and toxins.

An Initiative to Accelerate Anti-Aging Research:

Never before has such a volume of scientific knowledge existed about the underlying mechanisms of aging and how they may be thwarted. A growing number of researchers are predicting major advances in our ability to slow and reverse degenerative aging processes. One obstacle is the bureaucratic regulations that slow the development of new medical technologies. An even more troubling concern, however, is an epidemic of apathy as it relates to providing funding for promising age-reversal research projects.

Those with disposable income and assets donate monies to all kinds of so-called charities, yet overlook research that could help them live in a youthful state of health for a very long time. When one considers that aging is the disease that eventually kills us all, you would think that this is where the bulk of medical research emphasis would be focused. Instead, billions of dollars are squandered developing band-aid approaches to degenerative diseases instead of seeking to intervene directly in the aging process itself.

...

So what Life Extension has done is set up a website for the purpose of ascertaining how many humans today would be willing to assist in funding accelerated anti-aging research. Activist members have pledged to reach out to wealthy individuals to see if they are willing to help support aggressive research projects aimed at finding a cure for aging. If enough pledges of support are received, Life Extension and others will coordinate programs and present them to those who indicate a desire to contribute.

I will be interested to see how well this initiative proceeds; the LEF has a broad base of customers and readers, and it will be informative to see just how many of them can be converted from the mindset of supplement purchaser to the mindset of supporter of meaningful longevity science. There is a large gap between those two points on the cultural map, as demonstrated by the near complete lack of funds, attention, or interest flowing from the vast "anti-aging" marketplace towards serious research projects. The LEF spokespeople and mouthpiece are very atypical examples of that industry, sad to say, and there is no useful connection between the bulk of the industry and real longevity science. If there was, we'd have seen the effects already.

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

On the State of Cancer Stem Cell Research

An article from the Scientist: "Based on new intelligence, oncologists are making informed battle plans to attack a particularly pernicious enemy - the cancer stem cell (CSC). Controversial though they are, cancer stem cells are an incredibly promising target. If treatment-resistant cancer, and the metastases that transplant the cancer throughout the body, could be attributed to the actions of a single cell type, it could explain many of the treatment failures and provide a novel way to attack the disease. The idea that cancers are driven by cells with 'embryonic features' is an old one. Many cancers regress to a less differentiated state, expressing proteins that are usually expressed only in the embryo or during early development. It is only in the past 20 years or so, however, that additional observations led to the hypothesis that these embryonic-like cells were a separate subpopulation that fueled tumor expansion, much the same way that stem cells churn out the cells that make up a particular organ. ... In the past 5 years there has been an exponential increase in CSC research. This research has helped to resolve a number of controversies regarding identification of these cells and their role in driving tumor growth and mediating treatment resistance. Despite these advances, the CSC field is still in its relative infancy, and many questions and challenges remain. More than a dozen biotechnology and pharmaceutical companies are now vigorously pursuing CSC research. As a result, a number of early-phase clinical trials targeting CSCs are in progress. These studies and the later-stage efficacy trials that follow them should indicate whether successful targeting of CSCs significantly improves outcomes in cancer patients. If this is found to be the case, it may usher in the beginning of a new era of cancer therapy."

Link: http://the-scientist.com/2012/04/01/are-cancer-stem-cells-ready-for-prime-time/

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

Alcor's Caveats

Cryonics provider Alcor dedicates a section of their website to challenges and problems, and it is well worth reading: "When you buy a house, the seller is legally obliged to disclose any known defects. When you review a company's annual report, it tells you every problem that could affect the corporate share value. Since arrangements for cryopreservation may have a much greater impact on your life than home ownership or stock investments, we feel an ethical obligation to disclose problems that affect cryonics in general and Alcor specifically. We also believe that an organization which admits its problems is more likely to address them than an organization which pretends it has none. Thus full disclosure should encourage, rather than discourage, consumer confidence. ... As of 2011, Alcor is nearly 40 years old. Our Patient Care Trust Fund is endowed with more than 7 million dollars and is responsible for the long-term care of over 100 cryopatients. In almost every year since its inception Alcor has enjoyed positive membership growth. We are the largest cryonics organization in the world - yet in many respects we are still a startup company. We have fewer than a dozen employees in Scottsdale, Arizona and approximately 20 part-time independent contractors in various locations around the USA, mostly dedicated to emergency standby and rescue efforts. We serve fewer than 1,000 members and the protocols that aid our pursuit of the goal of reversible suspended animation continue to be developed. At the present time the technology required for the realization of our goal far exceeds current technical capabilities. Cryonics will not be comparable with mainstream medicine until our patients can be revived using contemporary technology, and we expect to wait for decades to see this vision fulfilled. Nevertheless, we have made important progress by introducing brain vitrification to improve patient tissue structure preservation. Alcor shares some of the characteristics of startup companies. The organization is understaffed in some important areas and lacks as much capitalization as would be desired to support maximum growth. Limited resources prevent the organization from hiring as many highly qualified and experienced personnel as desired, and sometimes we have to postpone enhancements to equipment and procedures." I think that this is a great document, and Alcor staff are to be congratulated for publishing it - absolutely the right thing to do.

Link: http://alcor.org/problems.html

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

Copy Number Variations Correlate With Mortality Rates

A copy number variation is either a large deletion or repeat of a sequence in your DNA. We all have them, and some people have more than others:

Copy-number variants (CNVs) are a source of genetic variation that increasingly are associated with human disease. However, the role of CNVs in human lifespan is to date unknown. To identify CNVs that influence mortality at old age, we analyzed genome-wide CNV data in 5178 participants of Rotterdam Study (RS1) and positive findings were evaluated in 1714 participants of the second cohort of the Rotterdam Study (RS2) and in 4550 participants of Framingham Heart Study (FHS). First, we assessed the total burden of rare (frequency 1%) CNVs for association with mortality during follow-up. ... We observed that the burden of common but not of rare CNVs influences mortality. ... A higher burden of large (?500 kb) common deletions associated with 4% higher mortality.

We might speculate on what this means - and it's interesting to do so in light of the present debate over the role of nuclear DNA damage in aging. Is having generally more ragged DNA a bad thing in and of itself, or is it instead a marker for poor quality in other important biological processes, such that the DNA repair and copy checking mechanisms that exist to prevent this sort of issue from coming about in the first place? Only a handful of CNVs have been linked to raised risk of specific diseases, but that there is a general correlation with mortality rate suggests that researchers will find many more specific issues and areas of enhanced risk if they go looking for them.

Fortunately, the long age in which we humans were at the complete mercy of our inherited DNA is coming to a close - it'll be a fading memory only a century from now, something to look back on with mild horror, much as we look back on the comparatively recent ages in which infectious disease was a scourge. One of the great benefits of biotechnology is that every advance will allows the medical community to balance a small part of the genetic heritage we came into this world with. Some people enter the game with a bad hand: that matters less now than it did in the past, and it won't be too many decades more before it hardly matters at all - the sooner the better, I say.

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