Here's a question for you: why does the triumvirate of astrophysics, astronomy, and cosmology get such good press and widespread public approval in comparison to, say, the fundamental life sciences? I have to think it has something to do with the succession of scientists who evolved into successful media figures, educators, and advocates for their field, such as Carl Sagan, the present day Neil deGrass Tyson, or Patrick Moore - and I'm probably dating myself here by knowing of the existence of the latter. If asked to name noted scientists who went on to become media figures, off the cuff, I think I'd be hard pressed to quickly come up with more than one or two who didn't come from an astrophysical or similar background (right now my brain is delivering Attenborough, Dawkins, and blank). So clearly there's been a lot of groundwork accomplished over the past decades: bringing the broad field of physics and cosmology to the masses, and along the way gaining public support for the ongoing and often thankless work of understanding the universe and its myriad components.

A cynic might think that that having a massive government agency like NASA floating around for a good number of decades and spending lavishly on flashy programs intended in part to assure its own popularity might have something to do with it. I'd be that cynic, but it seems to me that most of the comparatively less popular and less beloved fields of scientific research are also ridden by large government agencies in the US - big budgets and just as much need for popular support. So I do think that there's something interesting going on here in that small sliver of the media spectrum that scientists have colonized. Something we can learn from.

To be a media figure of this sort is a career path option that's certainly open to researchers who garner either sufficient fame or media experience across the years, but for best effect it requires you to remove yourself from the business of science. The scientific community tends to behave like an aggravated immune system when confronted with someone who is both a media figure and actively publishing scientific research. Throughout history a great many people have subverted the scientific method for personal gain, using influence, fame, money, and other forms of corruption - and the modern media is all that rolled up into one neat package. Taking your work to the press before taking it to your peers is thus a grand heresy in modern science, one which leads to harsh judgement and excommunication. Consider what happened to the reputations of Pons and Fleischmann, for example. From that, all things associated with the mass media come to be eyed with suspicion by the rank and file scientists: publicizing a field is very welcome, but even the slightest hint of use of position to influence matters of publication is going to stir up wrathful mutterings at the very least.

So the scientist turned media figure must feel strongly enough about his field to want to be an advocate and educator, but must also essentially give up his work in favor of talking about what he used to do. Not, I think, the easiest of paths for someone who truly enjoys the scientific life.

Regardless, the future of longevity science - or the foundations of rejuvenation biotechnology, or SENS-like research, or whatever you want to call it - must come to include scientist-educators in the media. A Carl Sagan for this presently minor field must eventually arise: to my mind that will be one of the signs of growth and progress, meaning that it will happen as a matter of course along with (a) the expansion of the community of researchers actively working on ways to repair the damage of aging, and (b) increasing public awareness. But sooner is always better than later.

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

The cancer stem cell hypothesis suggests that a majority of cancers are driven and supported by a small population of errant stem cells, and that these cells are characteristic in ways allowing them to be identified and destroyed. Without the cancer stem cells, a cancer would whither. In other words, cancer stem cells offer the hope that there are in fact broad commonalities in the mechanisms of different forms of cancer, and that this fact will lead to a unified, single technology platform and robust cures for even late-stage cancers.

The existence and universality of cancer stem cells is a hotly debated topic in medical research, and rightly so for the reasons given above. Good evidence and arguments can be found on either side. Is cancer something that can be solved through a single mechanism or group of very similar mechanisms? Or only some cancers? Or only few cancers? These are important questions, and the answers, when they arrive, will tell us whether the prospects are for many cures arriving soon or for a slow and incremental flow of therapies over decades.

Today I noticed a good introductory popular science article that walks through the present state of research and scientific thought on this topic, and provides copious references along the way. You might find it interesting:

Take some cells from a tough-to-treat tumor, sort them, and inject each fraction into a different immunodeficient mouse, and only a small percentage of those cells will thrive and form tumors. This sort of experiment illustrates a concept that has been gaining traction within the cancer research community. Tumors contain a diverse mixture of cells, and only a handful of them can bounce back after treatment. That deadly minority can reproduce indefinitely and differentiate into a wide variety of cell types, just like stem cells. And often they express many of the same genes that are active in induced or embryonic stem cells and inactive in mature tissue.

...

The logic of pursuing therapies that might zero in on cancer stem cells is compelling to many. But the methods to evaluate such therapies' effectiveness, or to personalize cancer treatments according to stem cell markers, are not nearly as well developed. Without an array of proper markers, it's hard to tell whether drugs that target cancer stem cells are working as intended. ... Things are looking up for genetic analysis, but the poor reliability of cancer stem-cell-surface markers remains a confounding problem. For nearly a decade, biologists have known that antigens such as CD133 can be found on the surfaces of cancer stem cells. But these markers are not particularly specific.

...

But for solid tumors, which account for about 85% of all cancer diagnoses, the search for such stem-cell-surface markers is still in the early days. In such [cancers] cell-surface markers can vary from one type of cancer to another or even from one cell within a tumor to another. Until better markers are discovered [the] cancer stem cell field will remain somewhat embryonic.

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

A number of different research teams have recently demonstrated epigenetic markers that can be used to establish chronological age or predict life expectancy to various degrees. Here is another: "Aging has been associated with accumulation of cellular defects such as DNA damage and telomere shortening. On the other hand, there is accumulating evidence that aging rather resembles a developmentally regulated process which is tightly controlled by specific epigenetic modifications. ... All tissues of the organism are affected by aging. This process is associated with epigenetic modifications such as methylation changes at specific cytosine residues in the DNA (CpG sites). Here, we have identified an Epigenetic-Aging-Signature which is applicable for many tissues to predict donor age. ... This Epigenetic-Aging-Signature was tested on a validation group of eight independent datasets corresponding to several cell types from different tissues. ... The average absolute difference between predicted and real chronological age was about 11 years. ... It has to be noted, that chronological age is not identical with biological age and it is conceivable that some of the discrepancy between predicted and real age can be attributed to this difference - further research might facilitate determination of the biological age for personalized medicine."

Link: http://impactaging.com/papers/v3/n10/full/100395.html

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

SENS Foundation co-founder Aubrey de Grey recently presented at a meeting of the MIT Club of Northern California, and a two-part video record of the event was uploaded for those of us too distant in time and space to be there:

Join us for a fascinating discussion with Dr. Aubrey de Grey, Chief Science officer of the SENS Foundation (SENS stands for "Strategies for Engineered Negligible Senscence"), on the topic of "Regenerative Medicine Against Aging."

Dr. de Grey has been a provocative and polarizing figure in the scientific and medical communities' dialogue on the topic of life extension, and the approaches that will
lead to dramatic increases in quantity and quality of life.

According to Dr. de Grey, "the first human who will live up to 1,000 years is probably already alive now, and might even be today between 50 and 60 years old."

You might look back into the archives for an explanation of the 1,000 year life span: this is an estimated life expectancy for someone who does not age to death, thanks to a rolling series of advances in rejuvenation medicine that eventually add more than a year of additional life with each passing year of research and development. If you examine mortality rates due to other causes projected out over time, you see that an effectively ageless person will live for at least a millennium under the mortality rates of today, not considering any future reductions in the rate of death by accident thanks to advances across the board in technology.

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

There are a number of different lines of research focused on developing artificial blood or culturing blood to order from stem cells: "Clinical trials using blood created from adult stem cells are set to begin within the next two or three years, raising the prospect it could soon become routinely used where real blood is unavailable. Scientists are also developing alternative bloodlike substances which could be injected into the body as a 'stopgap' until an actual blood transfusion could be performed. ... modern doctors have minimised the risk of patients receiving infections such as Hepatitis A and C during transmission [but] blood produced from stem cells would avoid these risks and could be manufactured as type 'O-negative', which is produced by just 7 per cent of the population but is suitable for use in into up to 98 per cent of patients. ... It could also be used in certain hospital situations, for example in elective surgery, and save hundreds of thousands of lives in parts of the world where blood banks are not available. [Researchers have] developed a method of taking adult stem cells from bone marrow and growing them in the laboratory to produce cells which look and act almost identically to red blood cells. Once their technique is fine-tuned the team may consider using stem cells taken from embryos, or reprogrammed skin cells, instead of adult cells because although the end product does not mimic red blood as closely, they can be grown in much greater quantities in the lab. ... A more radical solution, which [researchers] say could be perfected within five to 10 years, is to develop a completely artificial alternative to blood which performs the same key functions and would be safe to use in patients of every blood type. This could involve packing haemoglobin - which carries oxygen around the body - into a synthetic cell-like structure, or using a chemical to hold the haemoglobin together so that it can be injected without the need for red blood cells."

Link: http://www.telegraph.co.uk/science/science-news/8850684/Artificial-blood-could-be-used-within-next-decade.html

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

The present work on tissue engineering of large structures, such as printing blood vessels and organs, or creating patient-specific organs for transplant using decellularization, will produce end results that rely on surgery - major surgical procedures in the case of organ transplants.

The trouble with surgery is that it is risky: major, involved surgeries bear a non-trivial risk of death even in the most advanced clinical surroundings, and that risk grows with age. Old people suffer a general frailty due to the damage of aging that makes it progressively less likely for them to survive any given surgical procedure. When you consider that every major organ is going to have issues if we live long enough without access to general biological repair technologies that remove the cellular and molecular damage that lies at the root of tissue dysfunction in aging, that's a bunch of major surgeries to look forward to.

So I believe we should look on the forthcoming phase of tissue engineering as a transitional period: organs will be built from scratch and transplanted until such time as the state of the art allows our existing organs to be incrementally repaired and rebuilt in situ instead. Eliminating the need for surgery is a big deal, and so in the long term I think that the future belongs to the branch of regenerative medicine that delivers populations of tailored stem cells into damaged tissue. As the research community becomes every better at precisely controlling the behavior and activities of cells, even that step of delivering new cells into the body may go away, to be replaced with adaptive drug-like therapies that issue commands to the body's existing cells through signaling pathways or induced epigenetic alterations, and which react to guide the ongoing state of repair.

Either way, surgery is not a desirable outcome - it's a least worst path at the best of times. In the future of medicine and aging, everything that can be achieved without surgery should be achieved without surgery, and we'll all be better off for it.

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

Via ScienceDaily: "Exceptional cognitive and physical function in old age leaves a tell-tale immunologic fingerprint, say researchers ... Likewise, older adults who have mild impairments bear a distinct immunologic pattern, too. ... Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed. The immune system is dynamic, and the changes it undergoes over time very much influence function. ... For the project, the team collected blood samples from 140 participants who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades and were 78 to 94 years old. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants' health and function, medical history and hospitalizations, and self-rated health, and assessed their cognitive and physical function using standard tests. Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells ... A closer look in the new study shows that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independently of the conventional ones. The functionally resilient elders also have a distinct profile of blood proteins called cytokines that reflect an immune-enhancing environment. ... Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and they have a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness."

Link: http://www.sciencedaily.com/releases/2011/10/111021125808.htm

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

The SENS Foundation has published a series of posts over the past year or so that follow progress in the development of immunotherapies to remove the age-related buildup of amyloid in the brain - much of it intended as treatments for Alzheimer's disease. Success here will, however, lead to a broader technology platform that might ultimately be turned against any damaging aggregate that builds up in the body with age. These aggregates contribute to aging itself, and so removing them is one necessary part of any comprehensive rejuvenation biotechnology package: "soluble and insoluble aggregates of beta-amyloid protein (Aß) and other malformed proteins accumulate in brain aging and neurodegenerative disease, leading progressively to neuronal dysfunction and/or loss. These have long been widely accepted to be drivers of Alzheimer's disease (AD) and other age-related dementias and neurological disorders such as Parkinson's disease, and it has recently become increasingly clear that neuronal protein aggregates are the main driver of 'normal' cognitive aging. To prevent and reverse the course of neurodegenerative disease and age-related cognitive dysfunction, the regenerative engineering solution is therapeutic clearance of extracellular aggregates (such as Aß plaques) and intracellular aggregates (such as soluble, oligomeric Aß). Immunotherapeutic Aß clearance from the brain is a very active field of Alzheimer's research, with at least seven passive, and several second-generation active, Aß vaccines currently in human clinical trials. ... . We now have a published report of preliminary findings from the first Phase I trial in an Aß-targeting vaccine with novel properties, and with the benefit of preliminary findings of outcomes that have only emerged with the experience of its forerunners in previous clinical trials."

Link: http://sens.org/node/2437

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

Nuts can generally lower your chances of suffering from cardiovascular maladies if eaten regularly throughout the week.

In the endless battle against heart disease and bad cholesterol, one type of food is standing out from the crowd of ‘would be’ super foods in terms of performance: nuts.

Several studies in the US and around the world have already attributed the power of nuts to lower LDL (or “bad cholesterol”) and generally improve a person’s cardiovascular profile.   According to a more recent investigation of the health benefits of nuts, headed by Loma Linda University researchers, consuming more than two ounces of nuts everyday for a few weeks produced long-lasting, positive effects.

The study involved more than five hundred respondents (males and females), none of which were taking any medications to control their blood pressure or cholesterol levels.  After approximately two months of natural “nut therapy”, the findings are as follows:

• 5.1% total cholesterol reduction
• 7.4% LDL (low-density lipoprotein) cholesterol reduction
• 10.2% reduction of triglycerides
• 8.3% improvement of bad cholesterol & good cholesterol ratios

Who will benefit the most from eating nuts?  The researchers have pointed out three key groups that will benefit the most, based on the respondent profiles and the results of the actual study:

• Individuals who are generally slim or of normal weight
• Individuals who already have a high level of “bad cholesterol” or LDL cholesterol
• Individuals whose main diet is composed mainly of high-fat foods

As can be seen from the three profiles, nearly everyone can benefit from consuming nuts on a regular basis.  And there are even more reasons to love this health food: according to Joan Sabate MD, one of the key researchers of the Loma Linda University study, nuts are packed with essential nutrients such as protein and fiber, which makes it an ideal snack.

If you like the idea of lowering your LDL cholesterol, you will not be stuck with oatmeal-based snacks anymore – you have a potent, alternative choice in the form of nuts.  All nuts will provide the same heart-healthy benefits.  So whether you love pecans or macadamias, your heart is still getting much needed help from the natural compounds found in nuts.

More reasons to love nuts

Need more reasons to start munching on nuts more often? Here they are:
1. Eating at least 1 ounce of nuts everyday can reduce your risk for developing coronary heart problems by a whopping forty percent.  That is almost half the total risk for this devastating group of cardiovascular diseases.

2. As early as 2004, the US Food and Drug Administration has already recognized the efficacy at which walnuts can lower blood cholesterol levels.  According to studies, walnuts contain lots of omega-3 fatty acids.  In addition to the heart-healthy fatty acid, walnuts also come with a healthy dose of fiber and vitamin E, which can help reduce cell damage due to free radicals.

Fiber on the other hand, encourages a healthy digestive process by helping ’sweep away’ the solid waste.  Getting enough fiber everyday is becoming a problem in modern society because many modern diets are high in fat and animal protein but low in roughage.  Eating walnuts and other nuts packed with fiber can help reduce the problems associated with low-fiber diets.

3. What about peanuts?  Peanuts are not really nuts; they come from plants that are part of the legume family.  Fortunately, peanuts have the same chemical compounds as most nuts.  So when you are eating peanuts (a type of legume) you are still getting the advantages of eating ‘true nuts’.

4. According to studies on pistachios, the nut can slightly reduce the LDL cholesterol in the body and raise the good cholesterol level.  I’m actually snacking on some pistachios right now as I’m writing this article!

5. Plan to get pregnant anytime soon?  If you do, eating nuts gives you access to a healthy source of folic acid. Folic acid is an important compound that prevents fetuses from developing physical and neurological abnormalities.

6. According to a study performed by researchers from the Physician’s Health Study, people who ate nuts at least twice a week are at less risk of dying from heart attacks than those who did not.

7. Peanuts contain the heart-healthy compound resveratrol which has been linked to the decreased incidence of heart disease in French society.  Though you get less resveratrol with peanuts, consuming peanuts regularly can supply you enough of the compound to ward off heart problems.

Tips for healthy munching

While nuts offer a lot of health benefits, it still has calories and some amount of fat.  Here are some tips for healthy munching:

1. Avoid eating salted nuts; the sodium used for flavor enhancement can raise your blood pressure.  Go for plain or unsalted commercial nuts.  Salt doesn’t really add much depth to a nut’s natural flavor.

2. If you are eating more nuts, you have to reduce your intake of other snack foods like potato chips and sodas.  (As an added note, if you like soda with your snacks, try substituting it with water or natural fruit juices).

3. If you like fresh greens, chop some nuts and add them to your salads. The texture and crunchiness of nuts will greatly improve your salad.  Also, you are getting even more fiber from eating fresh greens!

Sources:
aolhealth.com
heartdisease.about.com
cholesterol.about.com
cholesterol.about.com
http://www.vegan.org.nz
http://www.healthcastle.com

Discuss this post in Frank Mangano’s forum!

Around these parts Aubrey de Grey and the SENS Foundation should require no introduction. His advocacy and the Foundation's work on the science of repairing aging is well known, and has been mentioned here at Fight Aging! too many times to count. In my eyes, the Strategies for Engineered Negligible Senescence (SENS) continue to be the best extant plan for extending human life span as rapidly as possible - and within our lifetimes. The more funding that is devoted to realizing that plan, the better all of our futures will be.

I noticed that a podcast interview with de Grey is up at the Singularity Weblog:

Last time I had Dr. Aubrey de Grey on Singularity 1 on 1 the interview turned out to be a hit. In fact it is still by far the most popular podcast that I have done and the audio file has been listened to or downloaded over 30,000 times. Given Aubrey's popular appeal and the importance of his work, it is no surprise that I am very happy to have him back for a second interview. ... During this conversation I ask Dr. de Grey to discuss issues such as: the term natural death and its impact; the publicity and importance of two long-awaited documentaries about Ray Kurzweil - Transcendent Man and The Singularity is Near; traditional metabolic and more recent DNA tests such as the ones done by 23andMe and others; the slow developmental process of new drugs and therapies, and the problems of taking them from testing in lab rats to humans; the Thomas Malthus argument of overpopulation and Aubrey's reply to it.

Head on over there to watch or listen.

In the course of gently publicizing the Vegas Group project across recent weeks, I have been reminded that most people assume Reason to be a pseudonym. It isn't - Reason is actually my name. The way this works in the offline world, face to face, is much as follows:

Rude Person: Your name is Reason? Really? Really?

Me: Yes.

Rude Person: Oh.

And there it stops.

In the online world, sad to say, it is never that simple. To a certain extent I blame the growth of social network culture for the present level of confusion regarding privacy, anonymity, and abuse of anonymity - people have a way of conflating these three into one, when they are in fact quite separate items. Within the world of Facebook and the like, surrounded by the illusion of transparent vision into every trivial detail of the lives of others, people are forgetting both the simple courteous act of respecting privacy and the important differences between privacy and anonymity.

It should be remembered that the view of the lives of others provided by social networks is a fake: you are looking at a front, a presented facade. The only difference between that and email conversations - or exchanges of written letters - lies in the level of detail and immediacy. But I think that the ersatz appearance of lives lived like an open book cultivates a corrosive sense of entitlement quite unlike the cultural changes brought on by earlier forms of mass communication: that one is entitled to know a great deal about any other person, irrespective of their wishes on the subject. This is grossly impolite and disrespectful when carried from thought into action. Courtesy and privacy are intimately linked, and respect for a person must include a respect for their boundaries of privacy.

As it happens, I am a very private individual, something of a dying breed these days. I do not use social networks, as I gain little value from them. It isn't within my comfort zone for you to know where I work, what I look like, where I live, how I like my toast cooked, who I hang out with, who I connect with, and the thousand other trivialities that make up the evolving social network culture of zealous and carefully gardened oversharing. More and more often these days, I am finding that the response to my desired level of privacy is outright hostility - that a person feels entitled to know these things about me, and that this knowledge is in some way required for even the most trivial of communications.

This would no doubt seem ridiculous to our ancestors of past centuries, who communicated their thoughts to the distant reaches of the world in long-form essays. A person was judged from afar by their words, and the name attached to those words was the most trivial of identifiers. If you cannot produce a measured response to the messages contained in the hundreds of thousands of words that comprise Fight Aging!, then how is knowing what I look like going to help you? It won't, of course, and neither will knowing how I like my toast cooked.

In short, I am private, not anonymous - and that fact shouldn't matter one way or another. Judge by words and actions, not by characteristics that have little relationship to either. For the vocal few who apparently care deeply about such things, I'll point out that you would have said nothing and felt fine if the tagline on this blog and my emails said "John Smith" or some other form of bland, generic name. Doesn't that indicate that your approach to considering anonymity is broken in some fundamental way?

Trehelose is known to be involved in yeast life span, and given in the diet can extend life in nematode worms. In animals closer to we humans, it has been show to stimulate autophagy, the collection of processes by which cells recycle damaged components and remove the unwanted build-up of metabolic byproducts. More autophagy seems to be an unqualified good, and shows up as a mechanism of action by which healthy life span is extended via calorie restriction (CR), exercise, and drugs that aim to mimic some of the biochemical changes caused by CR and exercise. This all makes sense: if damaged components are removed from cells more rapidly, they have less time to cause further damage themselves. The system as a whole is better maintained. So there is some impetus in the research community to develop the means to enhance autophagy in humans.

I noticed one small portion of that line of work today - an open access study in mice that used trehalose to stimulate greater levels of autophagy, and showed a reduction in the level of degeneration expected in their brains. Like many animal studies, the mice here were engineered to develop a form of neurodegeneration comparatively rapidly, so as to provide a model for assessment of possible treatments at a lower cost:

The accumulation of insoluble proteins is a pathological hallmark of several neurodegenerative disorders. Tauopathies are caused by the dysfunction and aggregation of tau protein and an impairment of cellular protein degradation pathways may contribute to their pathogenesis. Thus, a deficiency in autophagy can cause neurodegeneration, while activation of autophagy is protective against some proteinopathies. Little is known about the role of autophagy in animal models of human tauopathy.

In the present report, we assessed the effects of autophagy stimulation by trehalose in a transgenic mouse model of tauopathy, the human mutant P301S tau mouse ... Autophagy was activated in the brain, where the number of neurons containing tau inclusions was significantly reduced, as was the amount of insoluble tau protein. This reduction in tau aggregates was associated with improved neuronal survival in the cerebral cortex and the brainstem. We also observed a decrease of p62 protein, suggesting that it may contribute to the removal of tau inclusions. ... Our findings provide direct evidence in favour of the degradation of tau aggregates by autophagy. Activation of autophagy may be worth investigating in the context of therapies for human tauopathies.

Pleasantly, the authors paid some attention as to whether providing mice with trehalose causes inadvertent calorie restriction, something that plagues the studies of incautious researchers. The effects of calorie restriction are very strong, and if your prospective treatment happens to make the mice in your study eat less - well, those mice will usually do better than their counterparts, all other things being equal. But here:

Water consumption of the three groups (no treatment, sucrose-treated and trehalose-treated) was similar. Sucrose and trehalose had no impact on the animals' weights or coat aspects, suggesting that the health of the mice was similar among the three groups.

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

A number of studies in recent years have suggested that calorie intake is not the only thing that can alter metabolism to change longevity in lower animals: "Specific odors that represent food or indicate danger are capable of altering an animal's lifespan and physiological profile by activating a small number of highly specialized sensory neurons ... Recent research in model organisms and in humans has shown that sensory experiences can impact a wide range of health-related characteristics including athletic performance, type II diabetes, and aging. Nematode worms and fruit flies that were robbed of their ability to smell or taste, for example, lived substantially longer. However, the specific odors and sensory receptors that control this effect on aging were unknown. Using molecular genetics in combination with behavioral and environmental manipulations, [researchers have identified] carbon dioxide (CO2) as the first well-defined odorant capable of altering physiology and affecting aging. Flies incapable of smelling CO2 live longer than flies with normal olfactory capabilities. They are also resistant to stress and have increased body fat. To many insects, including fruit flies, CO2 represents an ecologically important odor cue that indicates the presence of food (e.g. rotting fruit or animal blood) or neighbors in distress (it has been implicated as a stress pheromone). Indeed, this group of researchers previously showed that merely sensing one's normal food source is capable of reversing the health and longevity benefits that are associated with a low calorie diet. They now establish that CO2 is responsible for this effect."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-04/plos-tss041410.php

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

The Methuselah Foundation formally launched the New Organ initiative earlier this year: a research and technology prize aimed at speeding up tissue engineering of replacement organs. Today the Foundation announced the New Organ 100:

Today, 3,000 people will die from organ failure, many due to the lack of replacement organs. In the U.S. alone, over 100,000 are stuck on a waiting list, and many more can't even get on a list.

We need a revolution in medicine, and we need it as soon as possible.

Regenerative medicine is coming of aging. Significant breakthroughs are beginning to happen, but the funding to move the science and technology forward remains woefully inadequate.

The Methuselah Foundation is announcing today the New Organ 100 to kickstart a visible, popular movement with a singular purpose: make regenerative medicine famous to achieve whole organ manufacturing within 10 years.

We invite you to be among the initial 100 New Organizers, the seeds of the movement who each make the same pledge: give $10 a month toward raising the New Organ Prize, and ask 10 friends and family to do the same.

The goal of the New Organ Prize is simple: to stimulate progress while demonstrating the rising demand for greater R&D funding. 100% of gifts go toward growing the prize. Every gift is matched by donors to support the New Organ Fund, which funds our operations and investments in startups advancing critical technologies, such as Organovo's 3D bioprinter and Silverstone Solutions' kidney-matching software.

Lee Downing was one of the lucky ones. When he got on the waiting list for a liver transplant, it was only 4,000 people long. After his transplant in 1988, he regained his health completely. He's been actively promoting organ donation ever since, working hard to enable others to receive the git of life that he was blessed with.

And after 24 years in the trenches, he's never felt as optimistic as he does now:

"It's pretty simple. We've tried everything, and we still haven't succeeded. I believe we need a revolutionary change in our approach to transplantation, and New Organ is it. Without it, more people are going to die, and even more people are to be added to the waiting list. The New Organ Prize, where modern medicine and state-of-the-art technology merge, may be the most significant impact we can make on the current paradigm of transplantation. It's going to safe lives."

No one has ever used a prize to build a movement for social change ... until now.

Will you join us?

The Methuselah Foundation has been steadily gearing up to focus attention on the big goals in tissue engineering for some years now. It's is worth remembering that the Foundation was one of the early investors in organ printing development company Organovo, for example - and the leaders of Organovo are prominently featured as sponsors and advocates in the New Organ 100 campaign.

If you agree with the New Organ goals - tissue engineered organs in the clinic, as fast as possible - then join in, spread the word, and donate.

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

Some mitochondrial DNA lineages are objectively better than others, as demonstrated by correlations with longevity in humans. Here is a correlation with dementia risk, which might be superficially explained by a greater ability to power fuel-hungry neurons, or greater resistance to mitochondrial damage over time: "Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increase neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia and haplogroup J participants experienced a statistically significant 8-year decline in 3MS, both compared with common haplogroup H. [Other variants were] associated with a significant decline in DSST score [or] 3MS score."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22785396

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

You might recall that a few years ago, researchers extended life in nematode worms by feeding them trehalose. Here, scientists link normal abundances of trehalose in yeast cells with the longevity induced by calorie restriction: "Our recent investigation of how a lifespan-extending caloric restriction (CR) diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact (1) the age-related dynamics of changes in trehalose concentration; (2) yeast chronological lifespan under CR conditions; (3) the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and (4) the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility, and aggregation throughout lifespan." Trehelose stimulates autophagy in higher animals, the all-important set of mechanisms that recycle damaged cell components, so one would expect it to be beneficial there as well.

Link: http://www.frontiersin.org/Integrative_Physiology/10.3389/fphys.2012.00256/full

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

Andrew Weil, who is something of an apologist for aging, here holds forth on the merits of intermittent fasting (IF) - shown to improve health and extend life in laboratory animals through mechanisms that largely, but not entirely, overlap with those of calorie restriction: "An IF regime works, proponents say, because it aligns with our evolutionary history. Over the 250,000 years that Homo sapiens have been around, food supply has waxed and waned. We evolved to take advantage of this fact, building muscle and fatty tissue during times of abundance, then paring it back during lean ones. Fasting periods accelerate the clearing-out of waste left by dead and damaged cells, a process known as autophagy. A failure of autophagy to keep up with accumulated cellular debris is believed by many scientists to be one of the major causes of the chronic diseases associated with aging. Occasional fasting also seems to boost activity and growth of certain types of cells, especially neurons. This may seem odd, but consider it from an evolutionary perspective - when food is scarce, natural selection would favor those whose memories ("Where have we found food before?") and cognition ("How can we get it again?") became sharper. Research indicates that the benefits of IF may be similar to those of caloric restriction (CR) in which there are regular meals, but portions are smaller than normal. ... The positive effects of IF have been chronicled in a variety of animal and human studies, starting with a seminal experiment in 1946, when University of Chicago researchers discovered that denying food every third day boosted rats' lifespans by 20 percent in males, 15 percent in females. A 2007 review by University of California, Berkeley, researchers concluded that alternate-day fasting may: 1) Decrease cardiovascular disease risk. 2) Decrease cancer risk. 3) Lower diabetes risk (at least in animals, data on humans were less clear, possibly because the trial periods in the studies were not long enough to show an effect). 4) Improve cognitive function. 5) Protect against some effects of Alzheimer's and Parkinson's diseases."

Link: http://www.huffingtonpost.com/andrew-weil-md/fasting-health_b_1557043.html

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

As I'm sure you all know by now, mitochondria are swarming powerplants within the cell, descendants of symbiotic bacteria that bear their own DNA separate from the DNA in the cell nucleus. Mitochondrial DNA provides the blueprints for proteins making up the machinery of a mitochondrion, but it isn't as well protected or as well repaired as nuclear DNA. Given that a lot of reactive compounds are funneled through mitochondria in the processes that keep a cell powered, it is only to be expected that mitochondrial DNA becomes progressively more damaged over time. The range of mechanisms that have evolved to deal with that damage cannot keep up over the long term, and as a result a small but significant portion of our cells fall into ruin on the way to old age, becoming populated by dysfunctional, damaged mitochondria, and causing a great deal of harm to surround tissues and bodily systems by exporting a flood of reactive biochemicals. You can read a longer and more detailed description of this process back in the Fight Aging! archives.

So that is one side of the issue of mitochondrial DNA damage and its contribution to degenerative aging - and that in and of itself would be more than enough to make mitochondrial repair biotechnologies a research priority. There are many different potential ways of fixing or rendering irrelevant mitochondrial DNA damage, and allowing mitochondria to continue to function as well as they did at birth for an indefinite period of time. The sooner one of them is developed into a working therapy the better.

In considering mitochondrial damage there is another, more straightforward process at work, however. Many types of cell normally operate fairly close to the limit of the power provided by their mitochondria, including important cell populations in the brain and nervous system. As mitochondrial DNA damage accumulates with age, power production - meaning the pace at which adenosine triphosphate (ATP) is produced - falls off and cells either die or malfunction far more often than they did in youth. This is outlined in a recent open access review paper:

In aerobic cells the majority of ATP is produced by oxidative phosphorylation. This process takes place in the mitochondria where electrons that are donated from the Krebs cycle are passed through the four complexes (complex I-IV) comprising the electron transport chain (ETC), eventually reducing oxygen and producing water.

...

Many cells operate at a basal level that only requires a part of their total bioenergetic capability. The difference between ATP produced by oxidative phosphorylation at basal and that at maximal activity is termed "spare respiratory capacity" or "reserve respiratory capacity" ... Under certain conditions a tissue can require a sudden burst of additional cellular energy in response to stress or increased workload. If the reserve respiratory capacity of the cells is not sufficient to provide the required ATP affected cells risk being driven into senescence or cell death.

...

In this paper we hypothesize that mitochondria contributes to aging and age-related pathologies through a life-long continued decrease of the respiratory reserve capacity. The decrease sensitizes high energy requiring tissues to an exhaustion of the reserve respiratory capacity. This increases the risk of a range of pathologies that correspondingly are known to be age-related. Through a review of the effects of aging on the regulation of oxidative phosphorylation, we wish to substantiate this hypothesis. In addition, by using brain, heart, and skeletal muscle as examples, we will review how an age-related decrease of the reserve respiratory capacity is implicated in a variety of pathologies in the affected tissues.

Interestingly, there is a good case for arguing that it isn't just damage to mitochondria DNA (mtDNA) that reduces levels of power production in a cell's mitochondria - there are other changes taking place that turn down the dial, which in the absence of more definitive knowledge as to their causes could be classified either as programmed aging or as a programmed response to stochastic damage in other cellular systems:

Cumulative damage to the mtDNA is however, not the only contributor to the age-related decline of oxidative phosphorylation. Transcriptional profiling has revealed different regulation of nuclear genes encoding important peptides for oxidative phosphorylation when comparing young to old.

Either way, those mitochondria still need fixing. The biotechnologies capable of that job are on the horizon, and would be coming closer more rapidly if those involved in the work had a greater level of funding.

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

The aging of bacteria grants us insight into the very earliest evolutionary origins of aging: "When a bacterial cell divides into two daughter cells and those two cells divide into four more daughters, then 8, then 16 and so on, the result, biologists have long assumed, is an eternally youthful population of bacteria. Bacteria, in other words, don't age - at least not in the same way all other organisms do. ... [But] not only do bacteria age, but [their] ability to age allows bacteria to improve the evolutionary fitness of their population by diversifying their reproductive investment between older and more youthful daughters. ... Aging in organisms is often caused by the accumulation of non-genetic damage, such as proteins that become oxidized over time. So for a single celled organism that has acquired damage that cannot be repaired, which of the two alternatives is better - to split the cellular damage in equal amounts between the two daughters or to give one daughter all of the damage and the other none? ... bacteria appear to give more of the cellular damage to one daughter, the one that has 'aged,' and less to the other, which the biologists term 'rejuvenation' ... In a bacterial population, aging and rejuvenation goes on simultaneously, so depending on how you measure it, you can be misled to believe that there is no aging. ... We ran computer models and found that giving one daughter more the damage and the other less always wins from an evolutionary perspective. It's analogous to diversifying your portfolio."

Link: http://www.sciencedaily.com/releases/2011/10/111027150207.htm

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

PCG-1 is known to be connected to the benefits of calorie restriction in a range of species, and here researchers are working with flies: "One of the few reliable ways to extend an organism's lifespan, be it a fruit fly or a mouse, is to restrict calorie intake. Now, a new study in fruit flies is helping to explain why such minimal diets are linked to longevity and offering clues to the effects of aging on stem cell behavior. Scientists [found] that tweaking a gene known as PGC-1, which is also found in human DNA, in the intestinal stem cells of fruit flies delayed the aging of their intestine and extended their lifespan by as much as 50 percent. ... While little is known about the biological mechanisms underlying this phenomenon, studies have shown that the cells of calorie-restricted animals have greater numbers of energy-generating structures known as mitochondria. In mammals and flies, the PGC-1 gene regulates the number of these cellular power plants, which convert sugars and fats from food into the energy for cellular functions. ... The researchers found that boosting the activity of dPGC-1, the fruit fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies - the same phenomenon seen in organisms on calorie restricted diets. When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan."

Link: http://www.newswise.com/articles/fruit-fly-intestine-may-hold-secret-to-the-fountain-of-youth

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