From CTV News: "Researchers say they have discovered a new source of stem cells at the back of the eye, which they hope may one day provide a way to repair the damage from age-related macular degeneration, or AMD. ... [Researchers] identified the central nervous system stem cells in a single layer called the retinal pigment epithelium, or RPE, which lies behind the retina. ... The researchers salvaged the stem cells from the RPE layer in the eyes of more than 100 deceased donors, who ranged in age from 22 to 99. But the cells can also be isolated from the fluid surrounding the retina at the back of the eye, meaning they're also accessible in living people. ... You can literally go in and poke a needle in the eye and get these cells from the sub-retinal space. It sounds awful, but retinal surgeons do it every day. ... In culture dishes in the lab, the researchers were able to coax about 10 per cent of the RPE-derived stem cells to grow in the lab. Further prodding caused the cells to differentiate into, or give rise to, a variety of cell types - those that make bone, fat or cartilage. [The researchers] also generated a progenitor cell that carries some characteristics of one type of nervous system cell, although it was not fully differentiated. ... But the fact that we could make these cells that were part-way, that were immature, indicates to us that if we keep on manipulating them, going forward in the future, we should be able to find ways to create other types of central nervous system cells."

Link: http://www.ctv.ca/CTVNews/Health/20120106/macular-degeneration-stemcells-120106/

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

Uncoupling proteins (UCPs) govern the process of mitochondrial uncoupling, which changes the operation of the mitochondria in our cells to generate more heat and less of the cellular fuel chemical ATP. It's one of the mechanisms by which mammals regulate their body temperature. As for many processes that alter the behavior of mitochondria, uncoupling has an effect on life span, with more uncoupling usually leading to longer life spans:

Mitochondria are the power plants of your cells: they toil to turn food into ATP, used as fuel by the cell. In recent years, the eye of the research community has turned towards the process of mitochondrial uncoupling, whereby the processing of food is uncoupled from the generation of ATP. The result is less ATP and more energy in the form of heat - this is a part of the temperature regulation process in mammals, for example. It also appears to be important in calorie restriction, and therefore possibly important to longevity and aging.

The mitochondria are clearly very important in any consideration of aging, given that there are so very many ways to manipulate them to either shorten or lengthen life in laboratory animals. This is one of the reasons that any serious program of rejuvenation biotechnology has to include efforts to repair accumulated, age-related mitochondrial damage: there is an enormous weight of evidence telling us that mitochondria are a lynchpin in aging.

But back to uncoupling: there are compounds that promote uncoupling in mammals, such as DNP, but you can't just load up on an uncoupler and wait for the benefits to roll in. If your mitochondria produce too much heat for too long, you will simply roll over and die from something that looks a lot like heat stroke. Metabolism is a finely balanced machine, and taking it beyond its limits is easy to do once you bring this sort of process manipulation into the picture.

There exists a sizable amount of published work on uncoupling and longevity, and this field is, I think, helped by the fact that it borders on the study of calorie restriction, which is a heated area of research these days. A group that has published previously on human uncoupling protein variations and longevity in the past recently put out an open access paper on their research, which goes into more detail as to the findings.

Further Support to the Uncoupling-to-Survive Theory: The Genetic Variation of Human UCP Genes Is Associated with Longevity:

In humans Uncoupling Proteins (UCPs) are a group of five mitochondrial inner membrane transporters with variable tissue expression, which seem to function as regulators of energy homeostasis and antioxidants. In particular, these proteins uncouple respiration from ATP production, allowing stored energy to be released as heat. Data from experimental models have previously suggested that UCPs may play an important role on aging rate and lifespan. We analyzed the genetic variability of human UCPs in cohorts of subjects ranging between 64 and 105 years of age (for a total of 598 subjects), to determine whether specific UCP variability affects human longevity. Indeed, we found that the genetic variability of UCP2, UCP3 and UCP4 do affect the individual's chances of surviving up to a very old age.

...

Substantial evidence suggests that the ability of UCPs to reduce ROS and regulate energy utilization underpins the ability of UCPs to promote lifespan in various experimental models. In the present study we found that variants in UCP2, UCP3, and UCP4 significantly affect an individual's chances of becoming ultra-nonagenarians. The different localization of the proteins we found associated with longevity allows us to predict the areas where the uncoupling process may play an important role in survival at very old age.

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

Type 2 diabetes (T2D) is a lifestyle disease for the vast majority of people - you avoid it by refraining from overeating, becoming fat, and giving up exercise to turn sedentary. But some folk are more likely to succumb than others, given the same lifestyle choices, and different people descend into metabolic syndrome and then type 2 diabetes at different rates. It won't be too many more years before clinics will be able to tell you exactly where you stand on the downward spiral, and what your risks are: research "has provided the first proof of molecular risk factors leading to type 2 diabetes, providing an 'early warning' sign that could lead to new approaches to treating this and other human disease conditions. ... Taking an innovative research direction, [the] research team decided to map DNA methylation variations rather than DNA sequence variations, as was traditionally done. The team undertook a proof-of-concept study among 1,169 type 2 diabetes patients and non-diabetic controls. The results demonstrated the unique abilities of this novel research approach by revealing a clear-cut, disease-predisposing DNA methylation signature. This is a first report in the scientific literature of epigenetic risk factor for T2D. DNA methylation is a naturally occurring mechanism used to regulate genes and protect DNA from some types of cleavage. It is one of the regulatory processes that are referred to as epigenetic, in which an alteration in gene expression occurs without a change in the nucleotide sequence of the DNA. Defects in this process cause several types of disease that afflict humans. ... telltale methylation signature marks were also shown to appear on the DNA of young individuals who latter developed impaired glucose metabolism, even before the appearance of clinical diabetic manifestations."

Link: http://www.sciencedaily.com/releases/2011/12/111228134841.htm

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

If research and development in medicine is to move at anywhere near the pace it is capable of, given the rapid progress in all forms of underlying biotechnology, it must find a way to extend beyond the most heavily regulated regions. The most capable and largest research communities, like that based in the US, are also those with the least ability to locally develop their advances into medical products, thanks to the straitjacket of regulation from government bodies like the FDA.

For much of clinical development, this means that the expense imposed by the FDA makes progress either very slow indeed - and lacking in the competitive vigor that characterizes less regulated industries - or simply non-existent where the costs make a business of medicine unprofitable. Much of this weighing down of development is invisible to the casual observer: you cannot see lost opportunities, or count the medical technologies that might already exist if not for decades of the ball and chain of the FDA.

For some potential clinical applications it's worse than that: they are simply forbidden outright, with no path towards becoming permitted. Treatment of aging, development of rejuvenation biotechnology, is one such field in the US. The FDA doesn't recognize aging as a medical condition, and so will not approve treatments aimed to intervene in aging. Given that, raising funds for development of potential longevity science is very hard - there is next to no for-profit funding, and where that funding does exist, the regulatory path to approval steers development away from potentially useful treatments for aging into the sidelines of diabetes therapy or late-stage treatment of other age-related conditions. This effectively prevents any effective path towards longevity-enhancing therapies for healthy people from being followed within the US.

The way out of this mess, short of a revolution or collapse of government, is a systemic extension of the industry of clinical application of longevity science to include regions outside the US. The logical end result of the growing medical tourism industry is better defined roadway of connections and multinational organizations that will usher scientific developments from regions like the US into other parts of the world where they can be offered as clinical treatments. What has happened for stem cell therapies and medical tourism in the past decade is just a tiny beginning, a few first steps towards what must become a much more systematic, high-bandwidth, highly visible, reliable transfer of knowledge and funds - such that the US government can't just shut it down with a few threats of prosecution, such that every life scientist in the US knows how to monetize their research outside the US by shopping around for deals with offshore developers, and such that a large enough and competitive enough marketplace exists to make that shopping around a viable process.

This is a topic I have strong opinions on. So it's pleasing to see other people touching on these themes as well. Here's a post from the IEET blog on the intersection of visions for seasteading and visions for offshore medical tourism and clinical development:

What is the likelihood of seeing research vessels devoted to scientific research outside the bounds of national jurisdiction? The idea of relocating for the sake of circumventing law, in particular the notion of establishing new nations in international waters, is an idea typically initiated with liberty in mind. ... For instance, the idea of ships offering in vitro fertilization, flying Denmark flags, has been proposed to provide UK residents with a service, locally illegal. In the U.S., major delays in safe and effective regenerative medical services are likely. Regenerex, a company offering regenerative stem cell therapies, faces a potential halt in operation by the FDA. The company has been in dispute with the FDA over whether or not stem cell therapies should be considered 'drug' therapies. If the FDA succeeds in this dispute, Regenerex would then be required, by law, to discontinue treatments until appropriate certification is in place, which could be 'staggeringly expensive' and take several years.

Biotech companies researching longevity also inconveniently face roadblocks from the FDA, which only approves drugs aimed at treating diseases in a specific, defined manner. Aging is not currently considered a disease by the FDA, which makes the delay of essential treatment virtually inevitable. The need for extensive reform in policy is a reality of a good deal of near and future medical services, and both businesses and patrons are incentivized by the unique opportunity of circumventing regulatory systems.

I don't think that the sea is the answer on the scale of development industry needed to break loose the FDA's ball and chain - the goal seems to me to more a case of linking existing (land-based) infrastructure and development institutions, creating the roadway of knowledge, deals, and contractual ties, and the community that sustains that roadway.

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

Exercise mimetics are drugs that can replicate some fraction of the beneficial effects of exercise; their development is in the early stages. I don't think it's too far-fetched to suggest that the next ten years of exercise mimetic development will look a lot like the last ten years of calorie restriction mimetic development. In other words there will be a couple of well-funded, well-hyped lines of research that fizzle out with nothing to show for it, some solid advances towards identifying mimetics that, for one reason or another, aren't terribly practical for clinical development, and all of that against a backdrop of across-the-board progress in understanding metabolic processes that relate to exercise and its long-term effects. But, you'll note, no actual products that are legally available for use by healthy people.

Absent the straitjacket regulation it would be a whole other story when it came to products and product development, of course, but we live in a world of centralized control and socialism for medicine for those regions that also boast the most active and capable research communities. It's unfortunate, and it needs to change.

In any case, here is an example of the sort of early stage work that will lead to exercise mimetic development. If you cast your mind back ten years or so, you'll see it looks just like the sort of research taking place into the mechanisms of calorie restriction back then.

We take it for granted, but the fact that our muscles grow when we work them makes them rather unique. Now, researchers have identified a key ingredient needed for that bulking up to take place. A factor produced in working muscle fibers apparently tells surrounding muscle stem cell "higher ups" that it's time to multiply and join in. ... In other words, that so-called serum response factor (Srf) translates the mechanical signal of work into a chemical one.

"This signal from the muscle fiber controls stem cell behavior and participation in muscle growth," says Athanassia Sotiropoulos of Inserm in France. "It is unexpected and quite interesting." It might also lead to new ways to combat muscle atrophy. ... Srf works through a network of genes, including one known as Cox2. That raises the intriguing possibility that commonly used Cox2 inhibitors - think ibuprofen - might work against muscle growth or recovery, Sotiropoulos notes. ... "It may be difficult to find a beneficial amount of Srf," she says. "Its targets, interleukins and prostaglandins, may be easier to manipulate."

And so this will lead to a tree of research spanning the next few years, in parallel to a web of other, similar spreading investigations of proteins and genes and their effects on exercise.

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

The onset of Alzheimer's is not a sudden thing, which reinforces the view of it as a lifestyle disease: "The first changes in the brain of a person with Alzheimer's disease can be observed as much as ten years in advance - ten years before the person in question has become so ill that he or she can be diagnosed with the disease. [Researchers] are studying biomarkers - substances present in spinal fluid and linked to Alzheimer's disease. The group has studied close to 140 people with mild memory impairment, showing that a certain combination of markers (low levels of the substance beta-amyloid and high levels of the substance tau) indicate a high risk of developing Alzheimer's disease in the future. As many as 91 per cent of the patients with mild memory impairment who had these risk markers went on to develop Alzheimer's within a ten-year period. In contrast, those who had memory impairment but normal values for the markers did not run a higher risk of getting Alzheimer's than healthy individuals. ... This is a very important finding with regard to the development of new therapies against the disease. All prospective therapies have so far shown to be ineffective in stopping the disease, and many people are concerned that the pharmaceutical companies will give up their efforts in this field. But these failures may depend on the fact that the new therapies were initiated too late. When a patient receives a diagnosis today, the damage has already gone too far." I'm not sold on this last comment, given the evidence suggesting that Alzheimer's symptoms are reversible.

Link: http://www.lunduniversity.lu.se/o.o.i.s?id=24890&news_item=5773

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

The popular press will give just as much attention to an advance that extends life in healthy laboratory animals as they will to a technology demonstration that even partially reverses an artificially induced shortness of life. This is a problem, because the former is worthy of our attention, while it is almost always the case that the latter is not. Here is another example of the type from today's news:

Researchers at the University of Pittsburgh Medical Center genetically altered mice to make them age faster, making them old and weak in a span of 17 days. The scientists then injected the mice with stem cell-like cells taken from the muscle of young, healthy mice. The result was they reversed the aging process. The rapidly aging mice lived up to three times longer, dying after 66 days, rather than 28 days. The cell injection also appeared to make the animals healthier, improving their muscle strength and brain blood flow.

No, they did not reverse the aging process. What these researchers achieved was to partially (very partially) ameliorate the unnatural form of accelerated aging that they themselves created in these mice - which could be due to any number of mechanisms that have no application whatsoever to the treatment of normal aging.

You might recall that this same talking point came up a little over a year ago in connection with research into telomerase and accelerated aging:

It's interesting stuff, but unfortunately this present research is being headlined as "scientists reverse aging in mice" - which is absolutely not what was accomplished. Reversing an artificially created accelerating aging condition by removing its cause is not the same thing as intervening in normal aging, and it will rarely have any relevance to normal aging. ... The bottom line is that it is really only worth getting excited over a study that shows extension of life rather than an un-shortening of life. It's all too easy to create short-lived mice and then make them less short-lived - hundreds of studies have achieved this result in one way or another.

But this seems a little too subtle for much of the media - or, more cynically, perhaps it's more a matter that the employees of those press institutions don't really care all that much about accuracy or background for so long as the page views keep rolling in.

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

Two supercentenarian genomes have been sequenced, and suggest that - as always - the roots of variations in human longevity are more complex than we'd like them to be: "Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging."

Link: http://dx.doi.org/10.3389/fgene.2011.00090

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

From Big Think: "The loss of a human limb is a tragedy. We know that once they're gone, mammalian arms and legs can't ever be restored. But if you cut off a salamander's leg - or tail - it will reappear in just a few weeks. ... Now, a new generation of longevity-seekers hopes to apply the power of amphibians like the salamander, the axlotl, and the worm to human medicine. ... In the future, if we had the ability to grow a brand new heart or parts of hearts with that person's very own adult stem cells, then when we know that they have heart disease, we could just replace the heart. All of those [costly] visits to the hospital, all of the drugs, won't be required. ... Better tools will enable us to repair people rather than just sort of patching them up for a little while until they get sicker and sicker. ... Over the past few decades, scientists have begun to understand exactly how the regeneration process works in nature. When a salamander is injured, a clump of cells called a blastomea forms at the site of the wound. Like embryonic stem cells, the blastomea are especially plastic. These cells are then triggered to de-differentiate and re-initiate growth. ... Debate remains over whether they're fully pluripotent, meaning that they have the ability to form any type of tissue, or whether the cellular dynamics merely have to be reprogrammed. ... The trick, of course, is applying this knowledge to human anatomy."

Link: http://bigthink.com/ideas/41794

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

Here is an example of the other use for stem cells: to grow tissue that can be used to test and understand specific diseases. "Researchers are applying new stem cell technology to use skin samples to grow the brain cells thought to be responsible for the onset of Parkinson's disease ... [the] team will be gathering data from over 1,000 patients with early stage Parkinson's disease and taking small samples of skin tissue to grow special stem cells - induced pluripotent stem cells (iPS cells). iPS cells can be generated from accessible tissue such as the skin and then used to generate specific types of cell. The researchers will use the iPS cells to grow dopamine neurons - the brain cells responsible for the production of dopamine, as it is these cells which die in patients with Parkinson's, leading to the onset of the disease. ... iPS cells provide new and exciting opportunities to grow and study dopamine neurons from patients for the first time. This technology will prove to be extremely important in diseases which affect the brain because of its relative inaccessibility - it's far easier to get a skin sample than a brain biopsy. Once we have neurons from patients we can compare the functioning of cells taken from patients with the disease and those without to better understand why dopamine neurons die in patients with Parkinson's."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-07/babs-scc_1071210.php

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

This research has been doing the rounds:

This week researchers from the Dana-Farber Cancer Institute reported that the length of telomeres - which shorten with age - determines virtually every aspect of aging from wrinkles and gray hair to the onset of dementia, diabetes, and heart disease. At least that was the case in the mice they studied in a report published in Nature.

"We think we've identified the core pathway that really helps explain many different theories of aging," says study co-author Dr. Ronald DePinho, a geneticist at Dana-Farber. "Our study provides a unified field theory for aging."

In a nutshell, once telomeres shorten to a particular length, aging accelerates. Shortened telomeres allow the cell's DNA to become damaged, which activates a gene, p53. This sets off a warning to shut down the cells' normal growth and division cycle until the damage can be fixed or, if not, the cells die. At the same time, cells with short telomeres have power plants, or mitochondria, that are no longer operating at full capacity. This leads to malfunction in crucial organs like the brain, heart, liver, and pancreas, as well as a loss of muscle, and eventually extreme weakness and frailty.

(The paper is at Nature if you're the sort who likes to read primary sources). That's an ambitious declaration from the researcher quoted above - I can only imagine it's taken somewhat out of context and then hyped up by the science writer for the introductory paragraph, as it is certainly the case that damaged mitochondria and shortening telomeres are only two of the possible reasons we suffer age-related degeneration. Many of the other causes of aging involve a build up of varying forms of damaging waste product that the body cannot remove - mechanisms which are quite capable of causing disability and death on their own, telomere shortening or no telomere shortening.

That said, telomeres, mitochondria, and p53 are all large and healthy areas of research when it comes to the biology of aging. I imagine that anyone would be pleased to produce good evidence that might mechanically tie them all together, such that one or more are secondary effects rather than primary causes. From an economic perspective, we should all be hoping that some of our present candidates for the primary causes of aging turn out to be secondary effects - because then we don't have to devote any time towards developing repair biotechnologies to fix them.

On a closer reading of the new research, I have to say that it looks to me very much like an independent confirmation of discoveries from 2007 and 2008 relating to mitochondrial damage, telomere length, and the enzyme telomerase. In a nutshell, it may be that telomere shortening is entirely driven by mitochondrial dysfunction:

Researchers have put forward evidence to suggest that telomere shortening is caused by accumulated damage to mitochondrial DNA - essentially collapsing two areas of intense interest for gerontologists down to one root cause, if confirmed. ... [It may be the case that] poorly functioning mitochondria lead to telomere shortening, and telomerase somehow improves mitochondrial function to prevent that shortening. This is in place of the more expected path of undoing ongoing telomere shortening by adding extra repeat sequences to the end of the telomeres - that being the better understood function of telomerase.

I don't immediately see anything in the Nature paper that would rule out this interpretation of the link between these two fundamental mechanisms of aging. Like the earlier researchers, this present group also found that boosting telomerase activity improved mitochondrial function, though I believe they are arguing that the improved function happens as a secondary result of interactions between telomere length and p53. There's certainly plenty of room amidst the uncertainty for contradictory interpretations at this stage.

A study showed that the intake of red wine containing polyphenols can inhibit the decline of vascular function associated with old age.

The function of the blood vessels has the natural tendency to decline in efficiency as the person grows older. And this has been linked to different age-related health conditions like cardiovascular disease. The good news is:  there’s red wine.

Polyphenols in Red Wine to Prevent Cardiovascular Disease

A study conducted by a team of French researchers found that dietary supplementation of red wine containing high levels of polyphenols can slow down the decline of vascular function, which is normally associated with aging. For their preliminary investigation, the researchers used rat subjects to observe the effects of red wine’s polyphenols to the cardiovascular system. They found that polyphenols can inhibit the dysfunction of the cell lining of the blood vessels called the endothelium.

The researchers from the University of Strasbourg, France said that their findings indicate that the intake of polyphenols through the regular drinking of red wine at a younger age can help reduce endothelial dysfunction and physical decline as the person grows older. They added that the mechanism behind the proposed health benefit of red wine is linked with the antioxidant property of polyphenols, or its ability to reduce vascular oxidative stress by inhibiting the production of the   enzyme NADPH oxidase, which has been found to be responsible for the hardening of the arteries and in increasing a person’s risk of developing cardiovascular disease.

The study, led by French scientist Valerie Schini-Kerth, used four groups of Wistar rats. The control group received 3 percent of ethanol while the second and third groups were given 25 and 75 milligrams of polyphenols from red wine per kilogram of body weight in 3 percent ethanol, respectively. The fourth group was given the antioxidant and NADPH oxidase apocynin at a dosage of 100 milligrams per kilogram of body weight a day in 3 percent ethanol. The rats were 16 weeks old at the beginning of the study and it continued until they were 40 weeks old.

At the end of the study, the researchers found that three groups that received supplementation of polyphenols had lower levels of age-related vascular oxidative stress in the area of the endothelium. In addition, the group that received higher supplementation of polyphenols had a lower decline in physical performance compared to the control group.

The Health Benefits of Red Wine

The moderate drinking of red wine has been considered good for the health due to its high antioxidant content. Antioxidants have been found to reduce bad cholesterol levels while increasing the good cholesterol in the body; inhibit the production of inflammatory enzymes; and protect the cardiovascular system against the damage caused by oxidative stress. Despite the numerous potential health benefits of red wine, medical experts are doubtful about encouraging people to start drinking red wine due to the harmful effects of alcohol abuse. But they still agree that the antioxidants in red wine are extremely good for the health, especially to the heart.

The studies supporting the health benefits of red wine show that it contains more antioxidants than any other alcoholic beverage. Red wine contains a group of antioxidants called polyphenols that had been found to protect the lining of the blood vessels against oxidative stress. The two main forms of polyphenols are flavonoids and nonflavonoids.

Flavonoids are found in different food sources other than red wine. These include cocoa, tea, onions, apples, grape juice and oranges. Nonflavonoids, on the other hand, are efficient in preventing the clogging of the arteries with fatty substances. The studies supporting these claims are only limited to animal subjects and studies on humans are yet to be performed. Amongst the widely studied nonpolyphenol antioxidant content of red wine is resveratrol.

Resveratrol in Red Wine

Resveratrol is primarily found in the skin surface of red grapes. Red wine is rich in resveratrol since it is fermented with the skin intact. Numerous studies have found that resveratrol is effective in preventing the accumulation of fatty substances on the inner surface of the arteries. Studies on mice show that resveratrol can reduce the risk of obesity and diabetes – health conditions that are risk factors of heart disease. But to come in proportion with the resveratrol dosage used in the mice subjects, a person would need to drink 100 to 1,000 bottles of red wine in a day. This is not a problem since food supplements containing high dosages of resveratrol are widely available.

Other related studies on resveratrol found that the compound can be effective in reducing the production of inflammatory substances in the body. Heart disease, certain cancers, diabetes and cardiovascular disease are triggered by inflammation. Further studies are yet to be conducted in order to clearly determine the health benefits of resveratrol to the human body.

Natural Ways to Promote Heart Health

Promoting a healthier heart starts with eating the right kind of foods and having sufficient exercise. Heart disease is the number one cause of death in the United States and in other parts of the world. Studies found that heart disease can run in the family, but they also suggest that heart disease can be developed by unhealthy diet and the lack of exercise.

The foods that we eat have the strongest influence over the condition of our health. A diet rich in fat, low in fiber and insufficient in nutrients can lead to a higher risk in developing certain health conditions like cardiovascular disease, diabetes, obesity and even cancer. But this can be reversed by simply increasing our intake of fiber and important nutrients, and limiting our consumption of foods rich in fats. An increase in the levels of bad cholesterol is a strong indication of increased cardiovascular risk. This can be controlled by eating more brightly colored vegetables and whole grain foods, and less red meat. The accumulation of cholesterol can lead to the formation of cholesterol plaques on the walls of the arteries which can lead to an obstructed blood flow.

Exercise is very important. Not only does it keep the body performing well but it also helps in improving metabolism and burning excess fats. Certain vices like smoking and binge drinking can also adversely affect the heart so it is advised that these be avoided.

Sources
nutraingredients.com
today.msnbc.msn.com
mayoclinic.com
healthtree.com
healthcastle.com
essortment.com

Discuss this post in Frank Mangano’s forum!

The UK Medicines and Healthcare Products Regulatory Agency found that a certain brand of traditional Chinese medicine contains an unspecified and unauthorized pharmaceutical ingredient.

Looking beyond the obvious, having excess weight contributes to a higher risk of developing certain diseases like diabetes and chronic illnesses. Different weight loss products and food supplements promise fast results without the need for exercise and restricted diet. This is alarming since some people are putting their trust on products that has not been duly recognized as 100 percent safe by medical experts.

Most weight loss supplements are commonly bought and used by people without the advice of physicians. It is alarming to find out that these health dangers are sold over-the-counter, with no prescriptions needed, and with no questions asked. The weight loss supplements market has become a multi-billion dollar industry and almost everyone seems to want to jump in and join the bandwagon.  Because of this, despite the strict regulations, some manage to sneak past laid out rules – and this explains the availability. This can be dangerous especially to people with pre-existing health conditions.

The UK Medicines and Health Products Regulatory Agency ordered for the recall of the product Herbal Xenical, or also known as Herbal Flos Lonicerae, after a doctor reported the hospitalization of a patient after taking the product.

MHRA Warns Public from Taking Non-prescribed Weight Loss Supplements

After taking the product Herbal Xenical, a patient from UK reported gastritis, palpitations, insomnia and abdominal pain, and was hospitalized for severe symptoms. The UK MHRA ordered the immediate recall of the product. Though they refused to name the contaminant responsible for producing the effects, previous reports had sibutramine to blame. The MHRA said that they will be subjecting the product for lab testing to determine the real cause of the patient’s complaints.

The MHRA has also issued a warning to people who are taking the product to stop using the product and to consult a doctor. The MHRA also took the opportunity to promote the THMPD or the Traditional Herbal Medicinal Products Directive which aims to more effectively regulate weight loss supplements.  Richard Woodfield from the MHRA said that since 2005, their department has discovered more than 280 weight loss food supplements that contain significant amounts of pharmaceutical substances that produces adverse effects to the body. He added that situations like what happened to the person taking Herbal Xenical is the reason why they are promoting the Traditional Herbal Registration to the EU in order to better regulate herbal weight loss food supplements. He also said that people have the right to know what they are taking in and that they are not treating a certain health condition only to result to a more severe side effect.

In a recent update, the MHRA confirmed that Herbal Xenical highly contains a banned pharmaceutical ingredient called sibutramine. The tests revealed that the product contains twice the amount of sibutramine that is allowed by the EU before the ingredient was totally banned due to alarming findings such as the increased risk of stroke, heart attack, seizures and hypertension. The UK agency strongly encouraged people who had bought the product prior to the recall to stop using it. They also appealed to people who had experienced side-effects to report to the MHRA through its Yellow Card Scheme.

Sibutramine has been found in botanical products sold as herbal weight loss food supplements long with other harmful substances like lignocaine, vardenafil, tadalafil, glibenclamide and sildenafil. These substances had also been promoted to fight erectile dysfunction.

Natural Ways to Lose Weight

Not all natural weight loss products are safe for the body. Numerous clinical studies had found that certain herbal weight loss supplements contain compounds that can be harmful to a person’s health and which can also increase the risk of certain health conditions like hypertension, cardiovascular diseases and even stroke. There is too little evidence showing that these products can be effective without resulting to severe side effects. Medical experts and health professionals encourage people who want to lose weight to just rely on the tried and tested natural means and methods.

The best approach to losing weight is by exercising more and by eating healthy foods. Limiting your calorie intake to a healthy level prevents the further storage of fat in your body and encourages stored fats to be used. Certain diet plans may work for others but this will not be the case for everyone. It’s easy to make your own diet plan as long as you know your body’s nutritional needs, the nutritional and calorie content of different foods, and the calorie restriction to help you lose weight without making you feel weak. Make sure to keep every meal low in calorie but rich in nutrition. Eating fruits and vegetables that are rich in minerals, vitamins and fiber can be the best option.

But the burning of fats and shedding of excess weight can’t happen without the help of exercise. Finding time and the right motivation is key to helping yourself stick to the habit. Some people will often lose their enthusiasm to exercise in most days of the week. But with the right approach and reason to keep on moving, you’ll be reaching your weight goal even before you start noticing it.

Make a commitment to yourself. But before anything else, understand that losing weight will take time and a lot of effort. Make permanent changes to your lifestyle and do it for the right reasons. Be focused and stay committed to your weight loss plan. For your plans to work, you will need to have the physical and mental energy to change your habits. You may also need to address certain stressors that are probable contributors to your gaining weight.

Setting a realistic goal can also help in making it happen. Aiming to lose a few pounds per week is better than hoping to lose so much in a month. Initially setting out short-term goals will help you understand your goals and your ability to lose weight. You can always make adjustments but try to set a threshold and set the bar higher each time.

Consistency is the key. Be consistent with your diet plan, exercise habits, and lifestyle change and understand that it is not a temporary commitment that you can abandon once you reached your desired weight.

Sources
nutraingredients.com
nutraingredients.com
nutraingredients-usa.com
altmedicine.about.com
mayoclinic.com
mayoclinic.com

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Dr Liebowitz is a three times Board Certified Emergency Medicine Physician who practiced at Cedars Sinai Hospital in Los Angeles for over 15 years. He experienced many of his patients not getting better and returning to the ER with so many complications from the medications they were taking, that he felt there must be a better way to heal. He studied Functional Medicine and Anti Aging Medicine and realized that people could become healthier when all the normal functions of the body are supported. He integrates multiple disciplines of medicine from 30 years of experience together into his own unique blend. By balancing hormones, supporting the immune system,detoxification along with optimal diet and exercise (His 5 Step REDDI Plan)the result is optimal health with minimal or no pharmaceutical medications.

Dr. Liebowitz was trained in Internal Medicine at USC, and worked as an Emergency and Trauma Physician for 15 years at Cedars Sinai Medical Center in Los Angeles. He served as the Medical Director at The Centinela Hospital Fitness Institute in Los Angeles, testing professional athletes from The Lakers, Clippers, Dodgers and PGA golf tour. He also served as the team Doctor for The Pioneer Triathlon Team, a professional triathlon team. As a member of the medical steering committee for Tri-Fed, the governing body of the Triathlon sport, he helped direct it into the Olympics. He was a member of the advisory board of Bally Health and Tennis and 24 Hour Fitness, as well as a Physician at the Pritikin Longevity Center in Santa Monica, California. He has been a lifelong athlete himself as a college swimmer and later a triathlete completing the grueling Hawaii Ironman three times. His pursuit of helping athletes perform to their maximum potential naturally led him t

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Are there limits on human longevity? Sure. Few people will make it past a hundred years of age in the environment of today's medical technology - but today is today, and the technology of tomorrow will be a different story. If you want to talk about longevity and mortality rates, you have to qualify your position by stating what sort of applied biotechnologies are available. Longevity is a function of the quality and type of medicine that is available across a life span.

It so happens that most of the advances in medicine achieved over the course of human history, the vast majority of which have occurred in the past fifty years, have solved problems that killed people early in life. Infectious disease, for example, is controlled to a degree that would have been thought utopian in the squalor of Victorian England. The things that kill older people are a harder set of challenges: great progress has been made in reducing mortality from heart disease in the past few decades, for example, but that is just one late stage consequence of the complex array of biochemical processes that we call aging.

The point of this discussion? It is that tremendous progress in medicine, including the defeat or taming of many varied causes of death and disability, has not greatly lengthened the maximum human life span as experienced in practice. The research community hasn't really started in earnest on the work on rejuvenation biotechnology that will achieve that end - the story of medicine to date has been work on other line items, or largely futile attempts to patch over the failure modes that lie at the end of aging.

There are things that need to be fixed that currently limit human life span. Since aging is only an accumulation of damage, there is in fact a gentle trend towards extended life as a result of general improvements across the board in medicine - perhaps one year of additional life with every five years of technological progress at the present time. On average, people with access to the modern environment of technology and support are suffering biological damage at the level of cells and molecular machinery more slowly across their lives. But this incidental life extension is slow going indeed.

Given this history of medical progress you will find many life science researchers and advocates who view the human life span as bounded - they look to past progress and extrapolate to assume that future progress can only carry on improving things within the existing human maximum life span. In other words that more and more people will live in good health closer to that maximum, but that the maximum is set in stone. There's even a name for this goal, "compression of morbidity".

This is a ridiculous view when considered in the light of reliability theory and aging, but it is widely held and therefore something that advocates for rejuvenation biotechnology must work to dismiss. The future of medicine in the next few decades is not about gaining a decade of life with no hope of pushing out human life span beyond 120 years - it is about building the alpha versions of medical technologies that can provide indefinite healthy life spans through periodic repair of the known forms of cellular and molecular damage that cause aging. But unless many more people come to understand this point, there will continue to be the same lack of support for research that will lead to radical change in the relationship of medicine and aging. Advocate and gerontologist Aubrey de Grey touches on these issues in a recent editorial:

Is there a biological limit to longevity?

Gerontologists and demographers have argued about this for a long time, with the balance of opinion heavily influenced by the changes seen in the wealthiest nations' "survival curves" - graphs showing, broadly speaking, the proportion of an initial population that survived to a given age. Until a couple of centuries ago, these curves looked very much like radioactive decay curves, because one's chance of dying at any given age was pretty much the same. As medicine emerged and we became protected from most infectious diseases, the curve became more rectangular, implying a biological limit that most people were getting fairly close to.

...

So, why am I exercised about this? Simply because the belief in a biological limit to longevity is very often elided into a belief in a medical limit. And unfortunately, this inference is being taken seriously by influential observers and commentators, with all that that entails for public policy going forward.

...

Technology is about transcending what nature has created. To say that the biological limits to longevity are any kind of evidence of what we can do with medicine is a mixing of apples with oranges of the most egregious nature. And the reason it matters, of course, is that those who have not the time or intellect to see through it have the power to dissipate society's enthusiasm for attacking aging, by reinforcing the age-old belief that it is as immutable as the heat death of the universe. The result is a delay in the defeat of aging with medicine, the unnecessary loss of life and the unnecessary perpetuation of the untold suffering caused by aging. This cannot be allowed.

We must clarify, loud and clear, that medicine is about transcending biology.

Just so.

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

Work on stem cell transplants in rats is outlined here: "Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Epidemiological studies point out that AD affects 5% of the population over 65, and, parallel with increasing lifespan, the incidence of disease will rise dramatically. Clinically AD is characterized by a progressive learning capacity impairment and memory loss, especially memories of recent events ... Adult neural tissues have limited sources of stem cells, which makes neurogenesis in the brain less likely. Stem cells transplantation seems to be a promising strategy for treatment of several central nervous system (CNS) degenerative diseases such as AD, amyotrophic lateral sclerosis (ALS), and Parkinson's disease ... The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. ... Two months after the treatments, cognitive recovery was assessed ... Results showed that MSCs treatment significantly increased learning ability and memory in both age- and [chemical]-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and [nucleus basalis magnocellularis] lesions."

Link: http://dx.doi.org/10.1155/2012/369417

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

A herd of mitochondria exists in every cell, producing the ATP necessary to power that cell. Damage to mitochondria is important in aging, but how damage progresses in a cell's mitochondrial population is complicated by the fact that these are not completely discrete and static entities. They multiply like bacteria (fission), can merge with one another (fusion), and can also exchange individual components of their molecular machinery - so damage can be both passed around or mitigated depending on circumstances. Here researchers build models to better understand this dynamic: "Mitochondria are organelles that play a central role as 'cellular power plants'. The cellular organization of these organelles involves a dynamic spatial network where mitochondria constantly undergo fusion and fission associated with the mixing of their molecular content. ... Mitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging ... We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the 'mitochondrial infectious damage adaptation' (MIDA) model according to which a deceleration of fusion-fission cycles reflects a systemic adaptation increasing life span."

Link: http://dx.doi.org/10.1371/journal.pcbi.1002576

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

The evolution of aging and longevity is a field in which it's still comparatively easy to make a mark and carve out an area of new theory. For most species it is still the case that ideas on their longevity are comparative unsettled: why they live as long as they do, what mechanisms may have determined their life span, and how it all fits in to the bigger picture of metabolism and the evolution of specific biological processes. There is far more data than any one group of researchers could hope to organize in a lifetime, and new information continues to flood in ever faster as the biotechnology revolution unfolds.

At some point this rich wealth of data starts to give rise to hypotheses that are more holistic: evolution as a system of systems linked by feedback loops, thousands of species interacting with one another in any given biome, and the evolution of each species highly connected to that of its peers. Embarking upon this level of modeling and understanding, all the way down to biomolecular processes, will keep evolutionary biologists busy for the next century or so, I'd imagine - and give them something to do with the staggering levels of computing power that will be available by that time.

Here is an interesting open access paper that gives a hint of the shape of this sort of future research, whilst considering the evolution of longevity amongst interacting species:

Various organisms (i.e., bacteria, fungi, plants and animals) within an ecosystem can synthesize and release into the environment certain longevity-extending small molecules. Here we hypothesize that these interspecies chemical signals can create [selective] forces driving the ecosystemic evolution of longevity regulation mechanisms.

In our hypothesis, following their release into the environment by one species of the organisms composing an ecosystem, such small molecules can activate anti-aging processes and/or inhibit pro-aging processes in other species within the ecosystem. The organisms that possess the most effective (as compared to their counterparts of the same species) mechanisms for sensing the chemical signals produced and released by other species and for responding to such signals by undergoing certain hormetic and/or [cellular housekeeping related] life-extending changes to their metabolism and physiology are expected to live longer then their counterparts within the ecosystem.

Thus, the ability of a species of the organisms composing an ecosystem to undergo life-extending metabolic or physiological changes in response [to] chemical compounds released to the ecosystem by other species: 1) increases its chances of survival; 2) creates selective forces aimed at maintaining such ability; and 3) enables the evolution of longevity regulation mechanisms.

So the researchers propose that such things as the ability of rapamycin (produced by soil bacteria) to extend life in mice or the beneficial effects of mammalian bile acid on yeast life span are late manifestations of cross-species evolutionary processes that have been going on since the very earliest epoch of multicellular life. The suggestion is that we should expect there to be a wide range of compounds produced by varied species that will have some beneficial effect on the life span of another species (such as by improving cellular housekeeping processes), because the existence of such relationships between species is a fundamental characteristic of diverse ecosystems produced by evolution.

Which is an interesting line of thought, and I look forward to seeing where it leads.

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

An article from Cryonics Magazine: "Cryopreserved patients must be cared for for at least decades and some anticipate centuries. During this time, some caretaker organization must look after the patients. This involves paying the rent and utilities, replacing liquid nitrogen, maintaining and replacing dewars, hiring and paying staff, and a host of other activities that must be done reliably and economically. The usual arrangement is for the patient to make a lump sum payment into a common fund, the interest from which will then pay the expenses of maintaining a group of patients in cryopreservation for whatever period of time might be required. At Alcor, the lump sum payment is made into the PCT (Patient Care Trust), and the payment made by each patient is the 'PCT allocation,' taken from the total payment made by the patient at the time of cryopreservation. Determining the appropriate amount of the PCT allocation can raise questions whose answers are not always obvious and can sometimes be quite dilemmatic. ... Contractual and financial arrangements must usually be in place before a patient can be cryopreserved. The financial arrangements involve payment for both the up-front procedures and long term care. These payments are usually bundled, and at Alcor the total amount of money that is required is called the 'funding minimum'. The funding minimum is usually paid with life insurance. ... The focus of this article is on the lump sum payment made into the common fund from the funding minimum by the patient at the time of the patient's cryopreservation."

Link: http://www.alcor.org/magazine/2012/06/11/the-allocation-of-long-term-care-costs-at-alcor/

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

Sarcopenia is the umbrella name for the progressive loss of muscle mass and strength with age - which may turn out to cover a range of separate mechanisms. The progression of sarcopenia appears to be reduced by the practice of calorie restriction, and might also be slowed by a range of possible therapies such as exercise and dietary leucine supplementation or targeting the myostatin gene and its protein product. Levels of inflammation also show up as a possible contributing factor - more chronic inflammation is a bad thing across the board.

Here is an open access paper that touches on much of what the mainstream research community is investigating when it comes to sarcopenia.

Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation.

...

Several researchers have investigated the effect of inhibiting myostatin to counteract sarcopenia using animals. Lebrasseur et al. found that treatment with a mouse chimera of antihuman myostatin antibody (24?mg/Kg, 4 weeks), a drug for inhibiting myostatin, elicited a significant increase in muscle mass and in running performance ... More recently, Murphy et al. showed, by way of once weekly injections, that a lower dose of this anti-human myostatin antibody (10?mg/Kg) significantly increased the fiber cross-sectional area (by 12%) and in situ muscle force (by 35%) of aged mice (21?mo old). These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for sarcopenia by inhibiting protein degradation.

Work on myostatin therapies is one of the topics worthy of greater attention here, as this seems like it would be a generally beneficial gene therapy for everyone - something that, given a good safety profile, most people would want to undergo earlier in life. The first step towards widespread availability for this sort of human enhancement is to develop the necessary medical technology in in the first place, of course, and these days that's only going to happen in the service of treating a specific medical condition.

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