A mainstream press article on exercise and aging: "As we age, our bodies change in ways that challenge athletic ability. But exercise also can slow down - and in some cases even prevent - some of the physiological ravages of time. ... A lot of things that we thought were just inherent to the aging process and were going to happen no matter what don't really have to happen if you maintain an appropriate lifestyle. ... How much can exercise slow down the ravages of aging? Potentially a lot. It will partially, but not completely, prevent arterial stiffening with age and completely prevent the dysfunction of the arterial lining that develops with age ... Exercise, it turns out, is probably as powerful as any other kind of prevention strategy or treatment that has been assessed so far. ... . For 21 years, researchers at Stanford University have studied the effects of consistent exercise on 284 runners 50 and older. In a 2002 article [they] reported that - 13 years into the study - a control group of 156 similar people who exercised much less on the whole than the runners had a 3.3 times higher death rate than runners as well as higher rates of disabilities. In a 2008 [study] they reported that after 19 years, 15% of runners had died, compared with 34% of the control group. After 21 years, runners had significantly lower disability levels than non-runners; their death rates from cardiovascular events, cancer and neurologic disorders were much lower than in non-runners - 65 of the runners had died of cardiovascular, neurologic and cancer events compared with 98 deaths in the control group."

Link: http://www.latimes.com/health/la-he-aging-physiology-20110901,0,5975284.story

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

Less us ponder the subject of having children in the face of the existence of aging coupled with the possibility of progressively defeating aging - perhaps to the point where some of us alive today will escape age-related death by the skin of our teeth. Or perhaps not if we don't get our act together here and now. Evidently we need to have children in order to have the chance of incrementally defeating aging by building ever better versions of a biological repair kit to reverse ever more of the damage that causes degeneration and death. This task is one of decades, long enough that it may be today's researchers who start the job, but it'll be younger hands that finish it - their children and grandchildren. Yet creating people is somewhat like drafting them into a war and a human condition that they didn't ask for:

There's a task we need you for, son, you and the rest of your generation. We may or may not manage to complete it, but we certainly won't without your help - and if we don't get this done, we're dead all too soon, a slow death, heavy on the pain and suffering. We'll be dragged away first so you get to see the end in all its horror, with plenty of sleepless nights to think it over before it happens to you as well. Oh yes, and most people don't see the need for any of this work and think the pain and suffering and death is just dandy. So that's the deal, a raw one all round - welcome to the asylum, son. No need to thank me.

I'm sympathetic to the hedonistic imperative view of pain and priorities in technological development, and I also think there's a fair but short-sighted argument to be made for nihilism along the lines of voluntary species extinction. It runs something along the lines of a utilitarian consideration of suffering, slavery, existence, natural rights, and similar concerns.

I call that short-sighted because, if we're going to be utilitarian, we should consider that the point and beneficiary of all this technological development - not to mention the bone mountain of suffering and corpses we stand upon and continue to build - is very much not us. Our own longevity and diminished future suffering is a tiny side-effect on the way to providing massively greater benefits to our future descendants, be they biological or machine intelligences. They will be so greatly endowed by the cumulative efforts in advancing technology that ensuring their existence (and ensuring that it comes about as soon as possible) will far and away outweigh our needs in any utilitarian consideration. We are short-lived, small in number, small in mind, and planet-bound evolved intelligences, while our descendants of future centuries will not be any of those things. There will be trillions of them, a near infinite variety of forms of mind, ageless, absent suffering, and hopefully wiser than us for it. They will exist because we, our forebears, and our children suffered the limitations and risks of our present existence in order to build the road that little bit further - and because we chose to inflict the same on others by bringing them into being.

So having children still looks to me largely like throwing new people into a horrible situation in order that some of them will try make it better - and with some hope that they might benefit as individuals, but also the great risk that they will not, and suffer greatly as a consequence. Beyond that, there is an abstract grail that will be enjoyed by people yet to come - our descendants made in biology or machinery - who we will likely never know, and whose era will be brilliant and golden beyond our imagining, but only if we strive to lay the foundation stones here and now.

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

Researcher João Pedro de Magalhães and colleagues are working on a new online resource: "We have developed a new web portal to integrate molecular, physiological ,and pathological age-related data that may be of interest. ... The Digital Ageing Atlas is a portal of changes covering different biological levels. There are currently portals for both humans and mice. The idea is to integrate molecular, physiological and pathological age-related data and create an interactive portal that serves as the first centralised collection of ageing changes and pathologies. ... It allows users to search and retrieve age-related changes at different levels, allowing a better understanding of the interplay between such changes and obtain new insights. We also think this will be an important new resource for modelling and for the systems biology of ageing and hope you will find it useful. Although so far we focused mostly on human aging, a preliminary mouse version of the portal is on-line already."

Link: http://human.ageing-map.org/

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

Via EurekAlert!: "When the body fights oxidative damage, it calls up a reservist enzyme that protects cells - but only if those cells are relatively young, a study has found. [Biologists] discovered major declines in the availability of an enzyme, known as the Lon protease, as human cells grow older. ... Lon protects the mitochondria - tiny organisms in the cell that convert oxygen into energy. The conversion is never perfect: Some oxygen leaks and combines with other elements to create damaging oxidants. Oxidation is the process behind rust and food spoilage. In the body, oxidation can damage or destroy almost any tissue. Lon removes oxidized proteins from the mitochondria and also plays a vital role in helping to make new mitochondria. ... To fight the oxidant, young cells doubled the size of their Lon army within five hours and maintained it for a day. In some experiments, young cells increased their Lon army as much as seven-fold. Middle-aged cells took a full day to double their Lon army, during which time the cells were exposed to harmful levels of oxidized proteins. Older cells started with a standing Lon army only half as large and showed no statistically significant increase in Lon levels over 24 hours." It is worth noting that the age of individual cells and the age of a person don't have much to do with one another except in some long-lived tissues where the same cells operate throughout life. But you might recall that mitochondrially-targeted antioxidants can increase life span in mice, and mitochondrial damage is important in aging - this research is consistent with all of that, and may lead to another way to extend life via protection of mitochondria.

Link: http://www.eurekalert.org/pub_releases/2011-08/uosc-nad083011.php

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

In recent years a number of researchers have used blood transfusions and mixing to discover and investigate systematic differences in biochemistry between old and young mammals. Many of the body's distributed systems use the circulatory system as a means of carrying signals and instructions throughout the body. Thus introducing old blood into the young or young blood into the old can bring about measurable biochemical changes that tell us more about the specific changes that occur with aging.

Aging is damage, but all of our biological systems are highly responsive to changing circumstances - so where there is damage, there will also be an evolved response to that damage. In theory that will be a coping response, but what evolution considers "coping" might not match with your opinions on the subject. For example, one form of characteristic response that occurs as we age is a progressive diminishing of growth and repair: stem cell populations stop doing their jobs as enthusiastically, for example, and the quality of our tissues suffers for it. It reduces the risk of cancer, but that's cold comfort for someone who is effectively being worn away, every bodily structure decaying faster than it is being repaired.

But back to the blood: here is a fresh example of what can be learned from mixing the blood of mice.

Stanford University School of Medicine scientists have found substances in the blood of old mice that makes young brains act older. These substances, whose levels rise with increasing age, appear to inhibit the brain's ability to produce new nerve cells critical to memory and learning. ... An early step in the Stanford team's study involved connecting the circulatory systems of pairs of old and young mice via a surgical procedure, so that blood from the two mice comingled. "This way, we could examine the effects of old mice's blood on young mice's brains, and vice versa. ... We saw a threefold increase in the number of new nerve cells being generated in old mice exposed to this 'younger' environment." ... In contrast, the young members of old/young mouse pairs exhibited fewer new nerve cells in the dentate gyrus than did young mice untethered to elders.

...

To identify specific circulating factors associated with aging and tissue degeneration or tissue regeneration, the researchers assayed 66 different immune-signaling proteins found in mice's blood. Six of these factors were elevated in both unpaired old mice and young mice that had been paired with older ones. At the top of the list was eotaxin, a small protein that attracts a certain type of immune cells to areas where it has been secreted by other types of cells. Highlighting this discovery's possible relevance to humans, [tests] conducted on blood and cerebrospinal fluid samples drawn from healthy people between the ages of 20 and 90 showed a parallel age-related increase in eotaxin.

Much of today's research is channeled into what is effectively a process of trying to patch over damage: the fastest way to try to move from laboratory to building something that the FDA might actually allow into the clinic is to (a) identify a single component is a biological system that might be manipulated to some palliative effect, then (b) design a drug to manipulate it with as few side-effects as possible. This two-step process is what much of the pharmaceutical industry and regulatory bodies are geared up for, and all they recognize. Try to do something different and your path will be longer and more challenging - see, for example, the fact that early stage stem cell therapies still cannot be obtained in US clinics, despite having been available overseas for a number of years now.

My point here being that work like that quoted above is interesting as a potential foundation for a way to patch over some of the issues that crop up with aging - but patching is a very different matter from repairing root causes, and will always ultimately fail. If better ways ahead are possible, and they are, then strategies involving patching should take second place in the priority queue.

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

I'll point out the results of a demographic and an associative study today: many of the leads followed up by life science researchers are first identified by showing there is some association between a particular trait or aspect of our biology and people who live longer, or have better health in old age. Firstly, I see that the Irish Longitudinal Study on Aging has published a weight of material, and a press release for those who like their summaries pre-digested:

TILDA is the most comprehensive study ever conducted on ageing in Ireland. Between 2009-2011, over 8,000 people aged 50 and over were randomly selected across the country and interviewed about many aspects of their lives including issues such as health, financial circumstances and quality of life. Almost 85 per cent of the participants also underwent a rigorous health assessment. The same group will be interviewed every two years until 2018.

...

A constant finding across the report is that those with higher levels of education and wealth are likely to enjoy better outcomes later in life.

Which reinforces data obtained from other large studies: the strong associations between wealth, intelligence, education, and health prospects in later life. These correlations have been discussed at Fight Aging! a number of times in past years. For example:

• Correlations in Biochemistry and Wealth
• Wealth and Longevity (for Individuals)
• Wealth and Longevity (for Populations)
• Revisiting the Link Between Intelligence and Longevity
• On Using the Tools to Hand

Moving on, you might recall hearing that grip strength is an excellent measure of frailty and thus risk of death in the old - and it correlates with all sorts of other measures of failing health and accumulating damage, such as the accumulation of AGEs. Here is another set of evidence in support of that biomarker:

We studied prospectively the midlife handgrip strength, living habits, and parents' longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu-Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965-1968, when they were 56-68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment.

...

Compared with people who died at the age of [less than] 79 years, centenarians belonged 2.5 times more often to the highest third of grip strength in midlife, were never smokers, had participated in physical activity outside work, and had a long-lived mother.

You can't do anything (yet) about the genes you were born with, but you can certainly work on the other line items listed above. You should expect good health to make a meaningful difference to your life expectancy - and bad health to make a meaningful difference in the opposite direction.

One of the reasons that work on heat shock proteins are attracting interest in the research community is that these proteins are deeply involved in cellular housekeeping processes. They are one of the components of the machinery of hormesis, wherein the body is improved by mild stress and a little cellular damage, because that stress causes repair and housekeeping systems to spring to life and work earnestly to make everything shipshape. Heat shock proteins are so named because they were first identified in the response to molecular damage caused by heat - but they are brought into play by all sorts of stresses that can cause damage to the delicate protein machinery of cells.

As is the case for autophagy, it is worth thinking about where we might be taken by the ability to boost the heat shock response on demand, or selectively alter and improve it. Beyond thoughts on slowing aging, calorie restriction mimetics, and modestly increasing human longevity, a number of mainstream research groups investigate housekeeping mechanisms as a possible way to treat neurodegenerative diseases. I noticed another example of this sort of work recently:

Protecting Cells: Evidence Found for a Neuronal Switch to Prevent Neurodegenerative Diseases

Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response.

"Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating? Can our body fix the problem? That is the conundrum. In our study, much to our surprise, we discovered that the nervous system sends negative signals to other tissues in the animal that inhibit the ability of cells to activate a protective heat shock response. The machinery to repair the damaged proteins is intact, but the nervous system is sending a signal that prevents it from doing its job."

When the signal from the nervous system was reduced, the cells' heat shock response returned, leading to elevated levels of special protective proteins, called molecular chaperones, that kept the damaged proteins in check

This is early stage work in nematode worms: we'll have to wait a few years to see how well it carries through into mice, let alone people.

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

From ScienceDaily: "It has been long known that stress plays a part not just in the graying of hair but in hair loss as well. ... Now, a team [that] was investigating how stress affects gastrointestinal function may have found a chemical compound that induces hair growth by blocking a stress-related hormone associated with hair loss - entirely by accident. ... Our findings show that a short-duration treatment with this compound causes an astounding long-term hair regrowth in chronically stressed mutant mice. This could open new venues to treat hair loss in humans through the modulation of the stress hormone receptors, particularly hair loss related to chronic stress and aging. ... the researchers had been using mice that were genetically altered to overproduce a stress hormone called corticotrophin-releasing factor, or CRF. As these mice age, they lose hair and eventually become bald on their backs, making them visually distinct from their unaltered counterparts. The [researchers] had developed the chemical compound, a peptide called astressin-B, and described its ability to block the action of CRF. ... researchers injected the astressin-B into the bald mice to observe how its CRF-blocking ability affected gastrointestinal tract function. .... About three months later, the investigators returned to these mice to conduct further gastrointestinal studies and found they couldn't distinguish them from their unaltered brethren. They had regrown hair on their previously bald backs."

Link: http://www.sciencedaily.com/releases/2011/02/110216185406.htm

I am not complacent about the cancers that no doubt lie in my future - just as they lie in yours. But I am not terribly concerned either; I give more thought to the fate of my wallet than to the fate of my flesh when it comes to cancer. By the time I hit the stage of life at which cancers are most likely to manifest, then the state of the art in safe and robustly effective cancer therapies will be impressive indeed. That will be true even if all that happens in between now and then is that the present technology demonstrations carried out in laboratories are developed into commercially available therapies ... and I'd expect far more progress than that to happen over a twenty year span of time.

Here are two more reassuring examples of ongoing development in biotechnology for those of us fortunately enough to have the luxury of time when it comes to cancer - even if we certainly don't have the luxury of time when it comes to aging itself.

Nanotechnology may lead to new treatment of liver cancer:

Researchers evaluated the use of molecular-sized bubbles filled with C6-ceramide, called cerasomes, as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell's plasma membrane and controls cell functions, including cell aging, or senescence. ... The beauty of ceramide is that it is non-toxic to normal cells, putting them to sleep, while selectively killing cancer cells

...

Cerasomes [can] target cancer cells very specifically and accurately, rather than affecting a larger area that includes healthy cells. The problem with ceramide is that as a lipid, it cannot be delivered effectively as a drug. To solve this limitation, the researchers use nanotechnology, creating the tiny cerasome, to turn the insoluble lipid into a soluble treatment.

...

Researchers [previously] observed that cerasome use led to complete remission in aggressive, large granular lymphocytic leukemia in rats. ... It is plausible that preventing liver tumor vascularization with cerasome treatment could induce widespread apoptosis, a genetically programmed series of events that leads to cell death in tumors

The Answer To Wiping Out Cancer Could Be World's First Chemical Guided Missile:

Current cancer treatments destroy the cells that form the bulk of the tumour, but are largely ineffective against the root of the cancer, the cancer stem cells. This suggests that in order to provide a cure for cancer we must accurately detect and eliminate the cancer stem cells.

...

researchers have [created a targeted] RNA aptamer, a chemical antibody that acts like a guided missile to seek out and bind only to cancer stem cells. The aptamer has the potential to deliver drugs directly to the stem cells (the root of cancer cells) and also to be used to develop a more effective cancer imaging system for early detection of the disease.

Many different research groups are developing many different competing methods of both targeting cancer cells and delivering existing chemotherapy compounds in a highly targeted way. The chemical compounds used in many existing cancer therapies could be the basis for very safe and very effective future therapies if only they could be delivered just to cancer cells, and in small doses that did not leak out into neighboring tissues. This is exactly the capability being demonstrated over the past few years in laboratories around the world.

The jellyfish Turritopsis nutricula is one of the few species whose members might be considered immortal, based on what is presently known of its biology. The life course of this jellyfish is very far removed from that of humans; even more so than that of the lobster, another marine species that might be immortal - though there researchers know far too little to make the call one way or another.

Immortality in the sea lasts right up until something larger eats you, of course. The form of agelessness enjoyed by Turritopsis nutricula appears to be an adaptation to periods of starvation: it can retreat to earlier stages of its life cycle, and in the process its cells alter their character in an usual way:

It starts out as a larva that eventually sinks to the bottom of the ocean and attaches to a sturdy substrate and continues development into a polyp that resembles a sea plant. The polyp then matures to become a free-floating medusa, what we commonly recognize as jellyfish resembling an upside down saucer with tentacles. ... However, during times of stress like a shortage of food, Turritopsis responds by beginning to reverse the process before eventually becoming a polyp again. From this point then, it can again develop into a sexually mature medusa when conditions become more favorable. Theoretically, it can repeat this process indefinitely as its cells undergo a process called transdifferentiation, a rare biological process whereby any non-stem cell can become a different cell entirely. It is still unclear whether only specific cells can only become other specific cells or if any cell in Turritopsis has the potential to become any other cell.

Unlike other long-lived or apparently ageless animals, the principle biological process of interest here is transdifferentiation - being able to produce any type of cell from any other type of cell without having to go through intermediary stages such as the generation and differentiation of stem cells. Modern stem cell medicine depends on techniques for controlling and changing the state of cells - to be able to engineer pluripotent cells from ordinary cells, for example, or produce unlimited numbers of a particular type of cell for research, transplantation, and tissue engineering.

When it comes to transdifferentiation, the hope is that we will eventually be able to learn how creatures like Turritopsis skip the stem cell step and go directly from one cell type to another.

Reliable control over that process for human cells would greatly improve the state of the art in the field of regenerative medicine - and in fact research groups in the space are headed in that direction already.

Spanish scientists "have generated artificial human skin by [tissue] engineering based on agarose-fibrin biomaterial. The artificial skin was grafted onto mice, and optimal development, maturation and functionality results were obtained. This pioneering finding will allow the clinical use of human skin and its use in many laboratory tests on biological tissues - which, additionally, would avoid the use of laboratory animals. Further, this finding could be useful in developing new treatment approaches for dermatological pathologies. ... The skin created in the laboratory showed adequate biocompatibility rates with the recipient and no rejection, dehiscence or infection was registered. ... The experiment [is] the first to create artificial human skin with a dermis made of fibrin-agarose biomaterial. To this date, artificial skin substitutes were elaborated with other biomaterials as collagen, fibrin, polyglycolic acid, chitosan, etc. These biomaterials [added] resistance, firmness and elasticity to the skin. ... Definitively, we have created a more stable skin with similar functionality to normal human skin."

View the Article Under Discussion: http://www.medicalnewstoday.com/articles/186185.php

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

Resveratrol, a naturally-occuring compound in wine, may help reduce cardiovascular disease and prolong life, new human study states.

Resveratrol is a naturally-occurring compound found in wines fermented from grapes.   This compound is a polyphenol and has been studied for many decades primarily because of the French Paradox: there is a low incidence of heart disease in France even though the French generally indulge in high-fat diets.

The French also smoke and drink a lot of wine throughout their lives.  One would expect that cardiovascular problems would be common, given the circumstances; however, something is keeping the French heart strong and healthy.  And according to Dr. Renaud, a French doctor from Bordeaux University, it was resveratrol that was to be given the credit.

Blood flow boost

In the United Kingdom, a human study (note – they used live human subjects for the test and not animals) researchers found out that 250 milligrams of resveratrol can help increase the blood flow to the brain, without producing any negative effects to a person’s cognitive capacity.  This fact alone, according to Dr. David Kennedy, signals a renewed interest in resveratrol and how it can affect vascular activity in the brain.

Another study from Harvard University showed that resveratrol was able to prolong the life of yeast cultures.  This study was done back in 2003, which actually helped increase resveratrol’s popularity with the media as a potential “eternal youth” pill.

Other studies showed that this polyphenolic compound was also capable of prolonging the life of other species such as mice and even nematodes.  What’s amazing about this compound is that it produces so many benefits and yet it’s just one type of molecule. It is as if Mother Nature designed resveratrol as a ‘heal-all’ for all living beings.

How much can you safely take?

It’s good to be always cautious and careful with anything that we ingest or consume.  Regular doses of resveratrol should not be given to children (that usually means kids below the age of 12) and pregnant or lactating women.  This is a general caution because there are still no conclusive studies done on the potential effects of this compound.

However, many researchers disagree with the warning about the dose.  According to James Betz, MD, tests show that at 1,000 mg of reseveratrol the polyphenolic compound failed to produce any significant negative effects to the test subjects.  Could it be possible that nature’s heal-all also doesn’t produce any side effects?

We leave this question open for the time being – it is up to medical researchers to prove or disprove.  But what we know now is this: resveratrol has a very big potential in prolonging the life of humans by protecting people’s hearts.  That is the main benefit and it is still the most interesting advantage to people who ingest resveratrol supplements.

Other benefits of resveratrol

This tough molecule does more than just protect the heart:

1. Resveratrol reduces inflammation in the body, which might benefit a lot of people in the long term because many medical conditions produce inflammation in the skin, joints, muscles and other body tissues.
2. Resveratrol reduces the incidence of blood clots, which may cause heart attacks, stroke, thrombosis, embolisms, etc.
3. Resvertarol is a natural anti-oxidant that can rid the body of harmful free radicals.
4. Resveratrol may also help in controlling cholesterol levels in the body (LDL cholesterol or bad cholesterol is its main target).

Having a hard time with high blood pressure? This polyphenol has been associated with lower blood pressure, too!

Sources:
nutraingredients-usa.com
mayoclinic.com
mayoclinic.com

Discuss this post in Frank Mangano’s forum!

Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, open access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in todays scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering bench to bedside research into clinical strategies.

Oxidative Medicine and Cellular Longevity was founded in 2008 by Professor Kenneth Maiese who served as the Editor-in-Chief of the journal between 2008 and 2011.

The most recent Impact Factor for Oxidative Medicine and Cellular Longevity is 3.516 according to 2014 Journal Citation Reports released by Thomson Reuters in 2015.

Oxidative Medicine and Cellular Longevity currently has an acceptance rate of 42%. The average time between submission and final decision is 62 days and the average time between acceptance and final publication is 64 days.

Go here to see the original:
Oxidative Medicine and Cellular Longevity An Open Access ...

Hormesis is here examined in the context of exploiting it to slow aging: "The process of aging is accompanied by a progressive reduction of biological dynamical sophistication, resulting in an increased probability of dysfunction, illness, and death. This loss of sophistication is inherent in all aging organisms. However, it may be possible to retard the rate of loss of biological complexity [by] exploiting the multiple effects of hormesis, through a wide range of challenges including physical, mental, and biological stress. Hormesis is widely encountered in biological systems, and its effects are also seen in humans. It is possible to use hormetic strategies [to] enhance the function of repair processes in aging humans and therefore prevent age-related chronic degenerative diseases and prolong healthy lifespan. Such techniques include dietary restriction and calorie restriction mimetics, intermittent fasting, environmental enrichment, cognitive and sense stimulation, sexuality-enhancing strategies, exposure to low or to high temperatures, and other physicochemical challenges. Current research supports the general principle that any type of a hormetic dose-response phenomenon has an effect that does not depend on the type of stressor and that it can affect any biological model. Therefore, novel types of innovative, mild, repeated stress or stimulation that challenge a biological system in a dose-response manner are likely to have an effect that, properly harnessed, can be used to delay, prevent, or reverse age-related changes in humans."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20662589

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

This is an era of data in the sciences - endless, vast stores of data, with more pouring in constantly from new studies. In most fields the infrastructure to manage that data is still under construction; in the life sciences, for example, the rapid advance of bioinformatics and biotechnology in general has outpaced the strategies for data management. The data infrastructure is lacking, even as it is being built up rapidly. This has consequences on the efficiency of research and the speed of progress, but researchers are not blind to this present state of affairs.

Here, for example, Maria Konovalenko of the Science for Life Extension Foundation presents at last year's SENS5 conference, calling for better and more systematic management of data in longevity research initiatives - which is effectively a form of advocacy for lowering the cost of exchange of information between research groups.

Traditionally evaluation of age-related changes is performed by physiological, functional and psychological tests, by visual examination and some biochemical analyses. There is a big gap between the molecular data of aging and their implementation in practice mainly because aging data is scarce and it gets lost in the stream of bio-medical knowledge. As we know only a few databases exist that concern the molecular aspects of aging and none of them describes age-related changes and phenotype context like cell type or tissues.

We propose creation of an open web-based Integrated Information System on Aging Biomarkers. The goals of the System: 1. Systematization of data on age-related changes happening on various levels of organization in humans and model animals 2. Systematization of experimantal data on interventions in aging processes in model animals 3. Integration of clinical data on the impact of various interventions on aging processes in patients 4. Creation of a basis for modeling of aging processes, therapeutic interventions and their impact on patients' health and longevity

When development of life extending therapies begins in any earnest way (as opposed the present expensive dabbling with metabolic manipulation to slightly slow aging), it will be necessary to start keeping score and measuring well. Even before then, and as I pointed out above, there is more data than can easily be made useful at this time - that has to change in order to build a better foundation for the next generation of research projects.

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

Via ScienceDaily: researchers "have made early retina structures containing proliferating neuroretinal progenitor cells using induced pluripotent stem (iPS) cells derived from human blood. And in another advance, the retina structures showed the capacity to form layers of cells - as the retina does in normal human development - and these cells possessed the machinery that could allow them to communicate information. ... Put together, these findings suggest that it is possible to assemble human retinal cells into more complex retinal tissues, all starting from a routine patient blood sample. Many applications of laboratory-built human retinal tissues can be envisioned, including using them to test drugs and study degenerative diseases of the retina such as retinitis pigmentosa, a prominent cause of blindness in children and young adults. One day, it may also be possible replace multiple layers of the retina in order to help patients with more widespread retinal damage. ... We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain."

Link: http://www.sciencedaily.com/releases/2012/03/120313185232.htm

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

By way of a follow-up to an interview last month on what are termed very small embryonic-like stem cells (VSELs), here is a recent open access review paper that outlines the present state of knowledge on this topic - which has some relevance to studies of longevity in addition to the broader field of regenerative medicine:

Very small embryonic/epiblast-like stem cells (VSELs) and their potential role in aging and organ rejuvenation - an update and comparison to other primitive small stem cells isolated from adult tissues:

One of the most intriguing questions in stem cell biology is whether pluripotent stem cells (PSCs) exist in adult tissues. Several groups of investigators employing i) various isolation protocols, ii) detection of surface markers, and iii) experimental in vitro and in vivo models, have reported the presence of cells that possess a pluripotent character in adult tissues. Such cells were assigned various operational abbreviations and names in the literature that added confusion to the field and raised the basic question of whether these are truly distinct or overlapping populations of the same primitive stem cells. Unfortunately, these cells were never characterized side-by-side to address this important issue. Nevertheless, taking into consideration their common features described in the literature, it is very likely that various investigators have described overlapping populations of developmentally early stem cells that are closely related.

...

[We believe that] during embryogenesis, some PSCs give rise to [populations of less potent tissue-committed stem cells (TCSC)s] but some survive in adult tissues as a backup population of PSCs that renews the pool of TCSCs over time. In this scenario, PSCs are precursors of TCSCs during organ/tissue rejuvenation and a source of these cells in emergency situations when organs are damaged (e.g., heart infarct or stroke).

...

a main goal of the molecular analysis studies was to explain why VSELs do not fulfill the in vivo gold-standard criteria expected for PSCs (complementation of blastocyst development and teratoma formation in immunodeficient animals), which are seen with [embryonic stem cells] and [induced pluripotent stem cells]. To explain this discrepancy, we observed that VSELs, in a similar manner as late migratory primordial germ cells (PGCs), modify the methylation of imprinted genes, preventing them from uncontrolled proliferation and explaining their quiescent state in adult tissues

...

we proposed a hypothesis that relates aging, longevity, and insulin/insulin-like growth factors signaling (IIS) to the abundance and function of pluripotent VSELs deposited in adult murine tissues. We postulate that a decrease in the number of these cells due to prolonged IIS negatively affects the pools of TCSCs in various organs and has an impact on tissue rejuvenation and life span. In support of this notion, we observed a significantly higher number of VSELs in long-living murine strains (e.g., Laron dwarfs and Ames dwarfs), whose longevity is explained by low levels of circulating IGF1 and a decrease in IIS. By contrast, the number of VSELs is reduced in mice with high levels of circulating IGF1 and enhanced IIS (e.g., growth hormone-overexpressing transgenic mice) compared to normally aging littermates.

...

a chronic increase in caloric uptake that elevates circulating levels of IGF1 and [insulin] may contribute over time to depletion of [VSELs] from adult tissues, affect the generation of VSEL-derived TCSCs, and thus negatively affect life span. This explains why mice that have high levels of circulating blood plasma IGF1 and enhanced IIS display accelerated depletion of VSELs and have a shorter lifespan than age-matched littermates.

Interestingly, it is often the case that life science researchers spend years investigating the same entity within the body from different directions, working in comparative isolation from one another and developing quite divergent nomenclature. It is only later on that lines are drawn between the dots and some unity imposed on that area of research - this is more or less what happened for lipofuscin, for example, the build up of many mixed harmful chemicals inside cells that occurs with aging. Lipofuscin contributes to many different age-related conditions, and for years went by many different names in different subfields of medical and biological science, and few of the researchers were picking up on parallel and useful research outside their specialty.

So, even aside from the evidence amassed, it is entirely plausible that there is a great deal of this unification and synthesis yet to happen for portions of stem cell research - but on the other hand cells are very complicated beasts. To a certain degree calling something a stem cell or a particular type of stem cell at this time is a form of pidgeonholing in the face of complexity: a cell is quite capable of being sort of a stem cell or somewhat stem cell-like, and different types of stem cell might be as different from each other as they are from non-stem cells - and their categories all blur at the edges. Stemness isn't the result of a single switch, and is rather much more like a collection of linked controlling mechanisms.

Insofar as this all touches upon calorie restriction (CR) and its effects on health and longevity, we should absolutely expect that calorie restriction in some way affects stem cell populations for the better. Stem cells are an integral mechanism of health, and it would be hard to explain how CR improves near every measure of health, slows aging, and extends life in diverse animal species without it causing some improvement in stem cell capacity and operation in addition to its other lower level mechanical effects.

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

Via ScienceDaily: researchers "have unveiled a new method for making synthetic collagen. The new material, which forms from a liquid in as little as an hour, has many of the properties of natural collagen and may prove useful as a scaffold for regenerating new tissues and organs from stem cells. ... Our final product more closely resembles native collagen than anything that's previously been made, and we make that material using a self-assembly process that is remarkably similar to processes found in nature. ... Collagen, the most abundant protein in the body, is a key component of many tissues, including skin, tendons, ligaments, cartilage and blood vessels. Biomedical researchers in the burgeoning field of regenerative medicine, or tissue engineering, often use a combination of stem cells and collagen-like materials in their attempts to create laboratory-grown tissues that can be transplanted into patients without risk of immunological rejection. Animal-derived collagen, which has some inherent immunological risks, is the form of collagen most commonly used in reconstructive and cosmetic surgery today. ... Despite the abundance of collagen in the body, deciphering or recreating it has not been easy for scientists. One reason for this is the complexity collagen exhibits at different scales. ... Scientists must next determine whether cells can live and grow in the new material and whether it performs the same way in the body that native collagen does. ... clinical trials, if they prove warranted, are at least five years away."

Link: http://www.sciencedaily.com/releases/2011/09/110908124507.htm

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

Polyamines have been of interest since spermadine was shown to extend life in mice. Another topic of growing interest is the influence of gut bacteria on metabolism and longevity, and here is research to link these two items: "In mammals, levels of polyamines (PAs) decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. ... The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations. ... We supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared [and] LKM512-treated mice survived significantly longer than controls; moreover, skin ulcers and tumors were more common in the control mice." A caution here is that this result may well involve inadvertent calorie restriction: any dietary supplementation may affect appetite and thus level of caloric intake, and all studies have to be considered in light of the fact that even mild calorie restriction has beneficial effects on mouse health and life span.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156754/

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

SENS5, the fifth biannual conference on the Strategies for Engineered Negligible Senescence, took place last week. Researchers working on ways - or the foundation of ways - to intervene in the aging process gathered together to talk about progress on the road to rejuvenation through biotechnology.

The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - to reverse - those changes, rather than merely to slow down their further accumulation.

It seems, however, that the participants were so caught up in the conference schedule that they largely failed to post reports or commentaries online. There's a little Twitter activity, and a couple of videos for one of the presentations, but that's about it. Perhaps this is a sign of maturity for the internet: later years in which eager self-publishers feel they can let their hair down and stop trying quite so hard. Material will be posted online in the weeks ahead by SENS Foundation volunteers, and that will hopefully include a video archive to match those for past SENS conferences. Meanwhile, you might take in the YouTube videos posted to date:

The videos are for this presentation, which is a discussion of one approach to finding a cheap and effective way of keeping telomeres from eroding without making them too long in the process - a complex and challenging problem that has kept a number of research groups and startup companies occupied over the past decade.

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