From the Independent: "It is one of medicine's mysteries: what has caused Britain's plummeting rate of heart disease over the last decade? Deaths from heart attacks have halved since 2002 and no one is quite sure why. Similar changes have occurred in countries around the world but the death rate in England, especially, has fallen further and faster than almost anywhere. ... The researchers looked at 840,000 men and women in England who had suffered a total of 861,000 heart attacks between 2002 and 2010. Overall, the death rates fell by 50 per cent in men and 53 per cent in women. ... For the last 70 years we have been in the grip of a heart disease epidemic that began in the 1940s, rose to a peak in the 1970s and then began to fall. All Western countries were affected and all followed broadly the same pattern. ... researchers conclude that just under half the decline in heart attack death rates in England over the last decade is due to better hospital treatment; the rest is due to changes in lifestyle and the widespread use of pills to lower cholesterol and blood pressure." One might theorize that - at the high level - increased heart disease across the last seven decades is a consequence of the fat and sedentary lifestyles that tend to accompany increases in wealth across the board, while reductions are largely due to improvements in medical technology.

Link: http://www.independent.co.uk/life-style/health-and-families/health-news/the-curious-case-of-the-vanishing-killer-6294626.html

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

Science recently hosted a live chat event with researchers Aubrey de Grey and S. Jay Olshansky, public figures who have debated their views on longevity science a number of times over the last seven years or so. The logs and viewer comments from the event remain available for those interested in viewing the discussion, but note that it takes a little while for the widget containing them to load.

Live Chat: The Science of Antiaging

Jennifer Couzin-Frankel: And here's a question from Roy: Does the paper titled "Clearance of p16 positive senescent cells delays ageing-associate disorder" published in Nature January, 2011, prove the Strategies for Engineered Negligible Senescence (SENS's) validity, i.e. extend lifespan by remediating damage? If so, are their other examples of experimental validation of SENS in animal models?

Aubrey: Roy: that paper is a great proof of concept for one component of SENS, the benefits of removing "death-resistant" cells. The experiment didn't show life extension, but it wasn't expected to, because to do that you have to fix all the things that limit lifespan, not just one of them. Yes, there are various other examples, such as the elimination of amyloid in mouse models of Alzheimer's and the introduction of stem cells (or the stimulation of their division) in various tissues. We'll see more of this soon, that's for sure.

...

Jennifer Couzin-Frankel: An interesting question from Morten: Why do you want to live longer (as I understand it at least de Grey is after living longer)? What can't you accomplish in a life time?

Aubrey: Morten: this is the most insidious misunderstanding of the work that I and other biomedical gerontologists do. We are NOT working to extend life for the sake of extending life. We are working to postpone the ill-health of old age, which will probably have the side-effect of extending life, but it's no more than that, a side-effect. I personally have no idea how long I want to live, [any] more than I have an opinion on what time I want to go to the toilet next Sunday. In both cases I know I'm going to have better information nearer the time, so it's idiotic to even think about it. However, I can tell you that I have at least 1000 years of backlog already (books to read, films to se...) - don't you? If not, why not?

S. Jay Olshansky: Morton. The goal of research in this area in my view is not to extend life. The goal is to extend healthy life. If we live longer, I consider that a bonus. However, I would encourage you to be asking the same question of those now working to combat heart disease, cancer, and stroke, and those who experience these conditions. Why [do] we all want to live longer? I believe what we are talking about here are interventions that enable us to live our lives healthy for as long as possible.

...

Comment From Guest: Couldn't you guys be focusing on pain control, quality-of-life and ending poverty and depression in the elderly?

S. Jay Olshansky: [Think] about this for a moment. In 1900 life expectancy at birth was about 45. Now it's about 80 for women and 76 for men. We gained 30 years of life -- most healthy. Wasn't that worth it? It's hard to imagine the goal of extending healthy life as being harmful in any way -- it would enable people to remain working longer if they want, or retire healthier for a longer time period. Health also begets wealth for individuals and populations. Goodness -- why are we working so hard to combat heart disease and cancer then?

There's a lot more there to look through; you should certainly read the whole thing.

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

Via Maria Konovalenko, here is another attractive poster on the biology of aging from some of the folk behind the Russian Science for Life Extension Foundation. There are more of these documents out there than are translated to English, more is the pity, but the supply of people who can make good technical translations in cutting edge life science from Russian to English (and have both the time and motivation to do so) is limited at the best of times. The image below is low-quality - click through for the full size version.

You might look back in the Fight Aging! archives for a few more of these posters:

• A Regenerative Medicine Roadmap from the Science for Life Extension Foundation
• Biomarkers of Aging and Age-Related Conditions

You'll also find other documents at the Science for Life Extension Foundation website (scroll down for the links) and if you're up for reading the original Russian, you'll find a great deal of similarly interesting material at researcher Alexey Moskalev's blog.

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

From EurekAlert!: "The muscles of elderly people and of people with type 2 diabetes contain lower concentrations of a protein known as PARL (short for 'presenilin-associated rhomboid-like'). PARL plays an important role within cells in remodeling power-generating mitochondria. It's PARL's job to oversee mitochondria's quality control, specifically by maintaining their integrity as the cellular components undergo normal processes of fission and fusion. The findings provide yet another link between insulin resistance and the function of mitochondria. ... When mitochondria aren't functioning properly, food doesn't get metabolized to the level that it should ... Instead of getting burned, fats accumulate in cells where they impair insulin's action. As mitochondria fail to work efficiently, they also produce more damaging free radicals. ... Relative to younger people, older people showed signs of insulin resistance. They also had fewer numbers of mitochondria and lower expression of the PARL gene. ... We hypothesize that impaired PARL function is an important risk factor for the development of insulin resistance in skeletal muscle by decreasing mitochondrial mass and energetics and increasing oxidative stress, thus contributing to impaired glucose metabolism. As insulin resistance continues to develop, mitochondrial function, oxidative damage, and PARL activity may decline further, leading to a vicious cycle that eventually contributes to the development of [diabetes] or other age-associated diseases, including sarcopenia."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/cp-nci042810.php

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

Chili peppers, one of the world's most beloved spices, is showing much promise in terms of reducing fat percentage when introduced to one's daily diet.

In a recent report from Science Daily, a new study suggests that chili peppers may just be the missing key to increased weight loss.  The new study shows that  a compound in chilies called capsaicin, which also makes a chili hot to the taste, is responsible for initiating specific changes in protein.

According to lead researcher Jong Won Yun, this could very well be the good news the world has been waiting for.  If chili peppers can be used on a particular scale for lowering body weight, then chilies can be utilized to combat obesity.

Chili vs. obesity

Obesity is one of the world’s leading causes of chronic, degenerative diseases like adult-onset diabetes, hypertension and other cardiovascular maladies.  Being overweight has also been linked to cancer in the prostate and even the development of asthma.

Yun’s study made laboratory rats confirm their initial hypothesis that capsaicin can help burn off the calories.  Two groups of test animals were both given diets in high in fat. The control group was given a capsaicin supplementation, while the other group of rat were not given the chili compound.

After the study, the control group had lost an average of 8 percent of body weight compared to the group that did not receive capsaicin.  It was also discovered that capsaicin can produce changes in up twenty types of protein found in fat.

While the study did not provide a conclusive explanation that capsaicin actually reduces body weight, it can be viewed as a pioneering study that explores the anti-obesity effects of the chili compound on the molecular level. The study was published in the Journal of Preteome Research.

Fight visceral fat!

There are two main types of fat that people have to deal with: regular fat, which is found above the muscle tissues and visceral fat, which lies underneath the muscles of the abdominal region.  So what is the big difference?  Visceral fat actually surrounds many vital organs, including the liver and intestines.  According to recent studies, visceral fat may also contribute to the development of adult-onset diabetes and other diseases.

In a study published in the medical journal Obesity, lead researcher  Dr. Gary Hunter states that just eighty minutes of exercise every week can help fight off the formation of deadly visceral fat.  Initially, the 97 respondents (composed of European-American & African-American individuals) were given a calorie-restricted diet plus a regular exercise regimen.

After the study, the respondents were asked to continue exercising at least eighty minutes a week.  A year later, the researchers measured the amount of visceral fat the respondents had and found out that the ones who continued exercising regardless of the exercise model did not regain harmful visceral fat. The study concluded that this type of exercise was effective in reducing visceral in both the European-American respondents and African-American respondents.

Vinegar vs. fat

Vinegar, a natural byproduct of bacterial action, fruit/vegetable and water, is now being studied for its potential benefit as a fat fighter.  According to Japanese researcher Tomoo Kondo, vinegar showed great promise as a fat fighter when an animal test showed that acetic acid can reduce up to ten percent body fat in test animals.

How does it work?  Well, the established belief was that acetic acid activates a particular gene in the body responsible for breaking down fat.  When the gene is activated, the body starts producing proteins that help break down the stubborn stores of fat.  When this happens, accumulation of fat is greatly reduced.

Low carbs diet for lower blood pressure

For many years now, proponents of weight loss diets and regular practitioners of medicine have associated too much carbohydrates in one’s diet with higher risk of developing high blood pressure and uncontrollable weight gain.  According to Dr. William Yancy, the lead author of the study, a low-carbohydrate diet might be a better choice than investing in weight loss medication like orlistat.

The study indicated that while weight loss medication like orlistat can reduce weight, it did not produce identical beneficial effects on the respondents’ blood pressure.  This was not the same for the low-carbohydrate group.  Nearly fifty percent of the respondents in the low carbohydrate group were able to reduce their blood pressure.  Some of them had such an improvement that they were able to discontinue medication.  Only twenty-one percent in the weight loss medication group experienced a reduction of their blood pressure.

Sources:
aolhealth.com
sciencedaily.com
sciencedaily.com
sciencedaily.com
sciencedaily.com

Discuss this article in Frank Mangano’s forum!

Here is an open access PDF format mini-review on what is known of growth hormone and aging - that less of it is generally better: "A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22261798

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

Empires end when an entrenched elite can spend from the public purse and take on debt without immediate consequence or forethought, destroying the value of their currency in the process. Assuming (perhaps optimistically) that present economic empires survive the next couple of decades, a combination of foolish promises and increasing human longevity will be the rock that sinks them. From Reuters: "Like the subprime crisis faced by banks in 2008, the risk of people living for up to 20 years after retirement seems to have crept up on an industry based on using historical data to calculate people's chances of an early death. Now, pension funds and insurers say the mounting burden of protracted pensions payments is increasingly concentrated on a small group of providers: them. ... Nowhere better can the process be seen than in Britain, which is facing a crisis resulting from a combination of pension reforms and increased life expectancy. ... The many arguments in favor of a sovereign bond linked to longevity rest on one fundamental expectation: if pension providers can't pay, or become insolvent, governments will have to. Longevity bonds could make the process neater, and more politically palatable, than the collapse of a pension provider." The problem is not that some groups made bad bets, or that many people relied upon those bets being good. The problem is that these groups and their supporters can conspire with governments to bail themselves out with public funds and debt heedless of consequences.

View the Article Under Discussion: http://www.reuters.com/article/newsOne/idUSTRE6360LP20100407

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

A general interest article on transhumanist visions of the future and immortality in the sense of the continued repair and reversal of aging through medical technology: "Immortality could be sneaking up faster than we can believe. Barely a month goes by without some new advance in organ replacement, and a recent operation to replace a boy's windpipe with one generated from his own stem cells was called 'embarrassingly simple' by the specialist in charge. Further breakthroughs could be made by the SENS Foundation, led by the radical immortalist Aubrey de Grey, with a brutally simple plan to give humans an unbeatable protection against cancer. This involves limiting human cells' ability to divide at cancerous levels, with regular top-ups from externally grown cells replacing worn-out tissue. If these technologies can hold to their promise, biological immortality, perhaps the most cherished goal of the transhumanists, may be with us in a few decades. A loose grouping of scientists, philosophers and sympathisers, with organisations such as the Oxford Future of Humanity Institute and Humanity+, transhumanists urge human progress through radical technological enhancement. With regards to immortality, I'm certainly a sympathiser: if a dictator was murdering tens of millions of people right across the world, we'd gladly do anything to overthrow him. And yet ageing, as eloquently put by the transhumanist philosopher Nick Bostrom, is a tyrant that kills us by the cartload - and what do we do to stop it?"

View the Article Under Discussion: http://www.guardian.co.uk/commentisfree/2010/apr/15/transhumanism-biological-immortality

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

Via the Methuselah Foundation blog: "Today Methuselah Foundation launched the NewOrgan Prize, the Foundation's new longevity prize specifically focused on advancing the development of replacement tissues and organs for humans. Its goal is to accelerate advances in regenerative medicine, which will become the standard of care for replacing all tissue and organ systems in the body within 20 years, according to the U.S. Department of Health and Human Services. The first research team to construct a whole new complex organ (heart, kidney, liver, lung, pancreas) made from a person's own cells - one that is functionally equivalent and successfully transplanted - will be awarded the NewOrgan Prize. The goal of the Methuselah Foundation NewOrgan Prize is to achieve this medical breakthrough within the next 10 years. Today's launch is a call to action for competitors, candidates and contributors who want to participate in this crucial medical challenge aimed at extending healthy human life. ... Based on our success in spurring medical advances with incentives provided by the original Methuselah Mouse prize, we anticipate that over $10 million will be raised by the time the NewOrgan Prize criteria is met - and the prize presented - to the leading medical R&D team. At minimum, $1 million will be awarded to the research team that develops a whole new human organ that is functional and successfully transplanted."

View the Article Under Discussion: http://blog.methuselahfoundation.org/2010/04/methuselah_foundation_launches_neworgan_prize.html

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

Manipulating the machinery of mitochondria - the respiratory chain that turns food into the chemical ATP that is used to power cellular biochemistry - can extend healthy life in a variety of species. Here, researchers dig deeper into the mechanisms by which this happens, finding that there are more than one: "In Caenorhabditis elegans longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation [that] reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We [compared] nuo-6(qm200) [to] nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, [as] well as expression of superoxide dismutases, mitochondrial heat shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. ... Most importantly, we found that [the] lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently."

View the Article Under Discussion: http://pmid.us/20346072

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

From the MIT Technology Review, a look at another form of first generation immune therapy aimed at cancer: "Last year marked a first for engineered antibodies - the European Commission approved a new cancer drug called Removab (catumaxomab), an antibody specially designed to grab both cancer cells and immune cells in such a way that the immune cell can kill the cancer cell. (The drug is undergoing testing for U.S. Food and Drug Administration approval.) Now a handful of similarly complex molecules, dubbed 'bispecific antibodies' for their ability to target two things at once, are in clinical trials. The two arms of these antibodies work together in different ways to treat cancer or other diseases, by bringing together two types of cells, as with Removab, by targeting two different types of receptors on the surface of a cell, or even using one arm to deliver drugs to specific cells targeted by the other. ... While the concept of bispecific antibodies has been around for decades, the approach has only recently shown clinical success. The field has been driven forward by new ways of designing and making the antibodies, which take advantage of advances in protein engineering, as well as the success of single-target antibodies, such as herceptin, that are already on the market." This is an example of the way in which targeting technologies and new strategies from the biotechnology labs are slowly filtering into the old school drug development pipeline.

View the Article Under Discussion: http://www.technologyreview.com/printer_friendly_article.aspx?id=24970

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

I believe it’s a grand waste of time to try to optimize your health through presently available methods. It’s very easy to get the 80/20 best expected outcome: exercise regularly, practice calorie restriction with optimal nutrition, and refrain from methods of self-harm such as smoking, jumping off tall buildings, and so on. This is not rocket science.

There is no scientific support for going beyond this to tinker with types of exercise, esoteric supplements, and the like, however. There’s no way to link your future life expectancy with your activities, and there is no good weight of evidence to suggest that any of the thousands of available options are better or worse for life expectancy than the 80/20 approach. There is always someone out there pushing a new fad, but that doesn’t make it right, useful, or legitimate. Maybe you’ll improve your life span by a few percentage points, and maybe you won’t. There is no way to tell, and the time and money easily wasted on that endeavor is better put to other uses that are far more likely to extend your healthy life span – such as supporting the research needed to produce rejuvenation biotechnology.

That all said, it’s possible to go too far in the direction of doing little but the basics for your health – if you are thinking of letting it all go and doing nothing for your health, that will have consequences. This view is illustrated in the post quoted below, wherein the author rejects calorie restriction on the basis that the present consensus view is that it won’t extend healthy life in humans by all that much. This ignores the amazing health benefits demonstrated in human studies to date – calorie restriction may or may not extend human life by more than a few years, but it certainly greatly improves measures of health and lowers risk of age-related disease. It seems silly to reject something shown to produce larger benefits for basically healthy people than can be gained by any presently available medical technology.

I want to live longer and help others do the same. I assumed the most effective way to do that is by understanding the science of aging and then engineering solutions to extend human lifespan. That is why I became a biomedical researcher and over the past several years I have pursued this goal almost single-mindedly.

When a 2004 study showed that reducing the calorie intake in mice extended their life by 42%, I enthusiastically embraced the results and even put myself on a calorie restricted diet. But, subsequently, a 2012 study showed that long-term calorie restriction may not have the promised benefits. On the contrary, fewer calories without the required nutrients might actually cause harm.

Calorie restriction is not the first such “promising” route that eventually did not live up to the promise, and it will not be the last. Antioxidants showed promise in holding back diseases caused by aging, but now we know that antioxidant supplements are more likely to shorten your life.

Earlier in May, researchers showed that reducing a protein called NF-kB in mouse brains modestly improved their lifespan. I am not holding out for this result either. Before too long, I’m sure there will be reports of severe side effects of manipulating levels of NF-kB.

Looking at the data I have come to the conclusion that “doing nothing” may be the best option in most cases. This may not be as pessimistic as it sounds and it is definitely not to say that research in fighting aging must not be carried out. When I say “do nothing”, I am assuming that you do not smoke or drink too much alcohol, and have access to medical care in case of injury. Such measures are bound to increase your lifespan.

But currently, not intervening in the aging process is more likely to help you live longer than trying any of the methods I’ve mentioned, not by a few months but by many years. Trying any of those interventions may actually cause harm, and will do so for the foreseeable future.

I agree with the basic thesis here, which is to be a late adopter and refrain from chasing the latest fads and data – this is an aspect of what I am arguing with my view on the futility of trying to optimize health past the 80/20 basics. But again, you can take it too far and throw the baby out with the bath water. Calorie restriction with optimal nutrition has an enormous weight of evidence gathered over decades backing its benefits and safety, and the same goes for regular exercise.

Link: http://lifeboat.com/blog/2013/05/do-nothing-to-live-long

Source:
http://www.fightaging.org/archives/2013/06/overreacting-in-the-direction-of-doing-nothing.php

Source:
http://www.longevitymedicine.tv/overreacting-in-the-direction-of-doing-nothing/

MANHATTAN, Kan., Nov. 21, 2019 /PRNewswire/ -- Libella Gene Therapeutics, LLC("Libella") announces an institutional review board (IRB)-approved pay-to-play clinical trial in Colombia (South America) using gene therapy that aims to treat and ultimately cure aging. This could lead to Libella offering the world's only treatment to cure and reverse aging by 20 years.

Under Libella's pay-to-play model, trial participants will be enrolled in their country of origin after paying$1 million. Participants will travel to Colombia to sign their informed consent and to receive the Libella gene therapy under a strictly controlled hospital environment.

Traditionally, aging has been viewed as a natural process. This view has shifted, and now scientists believe that aging should be seen as a disease. The research in this field has led to the belief that the kingpin of aging in humans is the shortening of our telomeres.

Telomeres are the body's biological clock. Every time a cell divides, telomeres shorten, and our cells become less efficient at dividing again. This is why we age. A significant number of scientific peer-reviewed studies have confirmed this. Some of these studies have shown actual age reversal in every way imaginable simply by lengthening telomeres.

Bill Andrews, Ph.D., Libella's Chief Scientific Officer, has developed a gene therapy that aims to lengthen telomeres. Dr. Andrew's gene therapy delivery system has been demonstrated as safe with minimal adverse reactions in about 200 clinical trials. Dr. Andrews led the research at Geron Corporation over 20 years ago that initially discovered human telomerase and was part of the team that led the initial experiments related to telomerase induction and cancer.

Telomerase gene therapy in mice delays aging and increases longevity. Libella's clinical trial involves a new gene-therapy using a proprietary AAV Reverse (hTERT) Transcriptase enzyme and aims to lengthen telomeres. Libella believes that lengthening telomeres is the key to treating and possibly curing aging.

Libella's clinical trial has been posted at the United States National Library of Medicine (NLM)'s clinicaltrials.gov database. Libella is the world's first and only gene therapy company with a clinical trial posted at clinicaltrials.gov that aims to reverse the condition of aging.

On why they decided to conduct its project outside the United States, Libella's President, Dr. Jeff Mathis, said, "Traditional clinical trials in the U.S. can take years and millions, or even billions,of dollars. The research and techniques that have been proven to work are ready now. We believe we have the scientist, the technology, the physicians, and the lab partners that are necessary to get this trial done faster and at a lower cost in Colombia."

Media Contact:Osvaldo R. Martinez-ClarkPhone: +1 (786) 471-7814Email: ozclark@libellagt.com

Related Files

curing_aging_booklet.pdf

Related Images

william-bill-andrews-ph-d.jpg William (Bill) Andrews, Ph.D. Dr. Bill Andrews is a scientist who has spent his entire life trying to defeat the processes that cause us to age. He has been featured in Popular Science, The Today Show, and numerous documentaries on the topic of life extension including The Immortalists documentary.

Related Links

Dr. Bill Andrews speech at RAADfest 2018 (Sept 21, San Diego, CA)

bioaccess: Libella's CRO partner in Colombia.

View original content to download multimedia:http://www.prnewswire.com/news-releases/breakthrough-gene-therapy-clinical-trial-is-the-worlds-first-that-aims-to-reverse-20-years-of-aging-in-humans-300963496.html

SOURCE Libella Gene Therapeutics, LLC

See more here:
Breakthrough Gene Therapy Clinical Trial is the World's First That Aims to Reverse 20 Years of Aging in Humans - P&T Community

One approach to stem cell therapy is to try to order existing stem cells to do more work, accomplished by introducing signaling molecules into the body - a drug, in other words. This methodology has reached the point of early clinical trials, as indicated in this press release: "Clinical-stage regenerative medicine company Juventas Therapeutics Inc. [has] started enrolling patients in a Phase 1 clinical trial to evaluate the safety and efficacy of its leading stem cell factor for treating heart failure. In preclinical studies of heart failure in pigs, JVS-100, as the factor is known, significantly increased cardiac function by promoting cell survival and increasing blood vessel formation in damaged hearts. JVS-100 works by encoding Stromal Cell-derived Factor-1 (SDF-1), a growth factor that in adults recruits stem cells from the bone marrow to create new blood vessels. The JVS-100-treated pigs showed significant improvements in cardiac function. ... We've led with heart failure because that's where our preliminary data was, and it's a great clinical opportunity. We also have strong data in the area of peripheral vascular disease and cosmetic wound healing. ... The factor can increase blood flow for patients who have peripheral vascular disease and accelerate wound closure and prevent scarring for patients who have had cosmetic surgery [so] we're looking to move both those toward clinic in the near future."

View the Article Under Discussion: http://www.medcitynews.com/2010/04/juventas-therapeutics-starts-phase-1-trial-for-heart-failure-therapy/

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

As reported a couple of days ago, researchers have again demonstrated a link between aging and NF-?B, altering its levels in the hypothalamus it to both modestly lengthen and shorten life in mice. This may be completely a matter of dialing down chronic inflammation in later life, or it may also touch on other common ground in the overlap between metabolism and aging such as insulin signaling.

In the course of their work, the researchers followed some of the connections in this biological jigsaw puzzle to study other proteins and genes involved in generating extended life in mice via inhibition of NF-?B in the hypothalamus. One of these is gonadotropin-releasing hormone (GnRH), and the researchers found that enhancing its levels in the hypothalamus has much the same effect as inhibition of NF-?B. This side of the research gained the attention of the fellow who runs Extreme Longevity:

Can GnRH Administration Reduce Aging?

[The scientists] showed that regular GnRH administration to middle aged mice increased the number of brain cells and reduced signs of aging in the animals. To wit they specially said “GnRH treatment (peripheral) reduced the magnitude of ageing histology in control mice,” and “GnRH led to an amelioration of ageing-related cognitive decline.”

But of course the holy grail question here is simply can regular peripheral administration of GnRH increase lifespan? I contacted lead author Dongshen Cai MD-PhD and asked if the group had any lifespan data on regular GnRH treatment.

“We don’t have lifespan data regarding GnRH treatment,” he replied.

Too bad. Imagine if simply a weekly or so injection of GnRH from early middle age onwards could lead to decades more good health and reduction of disease? [Clearly] this is an experiment that should be tried in animals right away. Fortunately Dr. Cai agrees, “it is in our plan,” he says.

It has to be said that I generally don’t think of this sort of study in these terms. I’m not looking to see whether there’s a treatment that can be pulled out, because in most cases a 20% life extension in mice by some form of metabolic manipulation (gene therapy, altering levels of proteins, and so forth) isn’t going to be all that relevant to the future of human longevity. For one, it’s not rejuvenation, it’s only slowing aging. Secondly, mice have very plastic life spans, as is the case for most shorter-lived species. All sorts of things that are either known to do very little to nothing for human life span or are expected to do very little to nothing for human life span can nonetheless extend life by 10%-30% in mice.

So what I see here in the NF-?B / GnRH work is the potential for a therapy that might be applied to modestly reduce inflammation or improve the metabolic profile of older people. Something comparable to rapamycin, in other words, a marginal gain. Perhaps it’s a little better than today’s best therapies that produce similar effects, and perhaps it’s not. I’ll wager that it’s not going to be as good as regular exercise and calorie restriction. So overall it’s not something that I’d give a lot of time and interest to. As a general rule if a research result isn’t producing actual rejuvenation then it’s not going to have the potential to be a part of greatly extending lives in humans. We have a medical industry presently near-entirely focused on picking mechanisms like this and then using them to produce palliative, marginally effective patches to slap over some of the end stage consequences of aging. The dominant paradigm is to try to alter metabolism late in the game for a small benefit, and without attempting repairing the underlying damage that caused all the harm in the first place. This is a paradigm doomed to poor results, high costs, and ultimate failure.

We have to move on past this methodology of medicine and clinical application of research. The future is SENS and similar projects that aim to repair the causes of aging rather than putting patches on the consequences. It seems fairly clear to me from the performance of the medical establishment to date that only repair can be reliably expected to grant us additional decades of healthy life.

Source:
http://www.fightaging.org/archives/2013/05/a-different-take-on-nf-b-and-the-hypothalamus.php

Source:
http://www.longevitymedicine.tv/a-different-take-on-nf-%CE%BAb-and-the-hypothalamus/

Shrikant MaliIndian Journal of Human Genetics 2013 19(1):3-8The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities ar…Source:
http://www.medworm.com/index.php?rid=7326951&cid=c_449_50_f&fid=33830&url=http%3A%2F%2Fwww.ijhg.com%2Ftext.asp%3F2013%2F19%2F1%2F3%2F112870

Source:
http://www.longevitymedicine.tv/delivery-systems-for-gene-therapy/

Naked mole rats are well studied by the aging research community: there are large colonies of naked mole rats in US laboratories, and a steady output of new papers on naked mole rat biology from numerous research groups. Their genome was sequenced in 2011, in advance of many other species that you might consider more pressing candidates. Naked mole rats are interesting to scientists for a number of reasons, the most important of which are that (a) they live nine times longer than similarly sized rodent species and (b) are immune to cancer. Researchers hope that there is something to be learned here about the relative importance of different metabolic processes in degenerative aging, and further that the biological mechanisms by which naked mole rats suppress cancer so effectively might lead to a form of cancer therapy for humans.

I noticed a couple of recent papers on the topic of naked mole rat biology, starting with the usual consideration of oxidative damage in aging, which is one of the areas where this species is strikingly unusual. An old naked mole rat has all the measures of a very high load of oxidative damage, but none of the degeneration that another rodent species would be exhibiting with those same measures. Their biochemistry in some way shrugs off the consequences of such damage – you might look at the membrane pacemaker theory of longevity for some further context on this research.

Elevated protein carbonylation and oxidative stress do not affect protein structure and function in the long-living naked-mole rat: A proteomic approach

The ‘oxidative stress theory of aging‘ predicts that aging is primarily regulated by progressive accumulation of oxidized macromolecules that cause deleterious effects to cellular homeostasis and induces a decline in physiological function. However, our reports on the detection of higher level of oxidized protein carbonyls in the soluble cellular fractions of long-living rodent naked-mole rats (NMRs, lifespan ?30yrs) compared to short-lived mice (lifespan ?3.5yrs) apparently contradicts a key tenet of the oxidative theory.

As oxidation often inactivates enzyme function and induces higher-order soluble oligomers, we performed a comprehensive study to measure global protein carbonyl level in different tissues of age-matched NMRs and mice to determine if the traditional concept of oxidation mediated impairment of function and induction of higher-order structures of proteins are upheld in the NMRs. We made three intriguing observations with NMRs proteins: (1) protein carbonyl is significantly elevated across different tissues despite of its exceptional longevity, (2) enzyme function is restored despite of experiencing higher level of protein carbonylation, and (3) enzymes show lesser sensitivity to form higher-order non-reducible oligomers compared to short-living mouse proteins in response to oxidative stress.

These unexpected intriguing observations thus strongly suggest that oxidative modification may not be the only criteria for impairment of protein and enzyme function; cellular environment is likely be the critical determining factor in this process and may be the underlying mechanism for exceptional longevity of NMR.

In another paper we find that naked mole rats also appear to laugh in the face of their version of amyloid beta, the aggregate that shows up in damaging clumps in late stage Alzheimer’s disease. Old naked mole rats naturally have as much amyloid beta as mice deliberately engineered to have high levels of amyloid beta, and apparently suffer few or no ill effects as a result.

Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer’s disease

Amyloid beta (A?) is implicated in Alzheimer’s disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of A? similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in A? levels in the individuals examined (2-20+ years).

The NMR A? peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR A? was less prone to aggregation than human A?. Nevertheless, both NMR and human A? were equally toxic to mouse hippocampal neurons, suggesting that A? neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of A? with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.

Source:
http://www.fightaging.org/archives/2013/05/recent-research-results-from-the-study-of-naked-mole-rats.php

Source:
http://www.longevitymedicine.tv/recent-research-results-from-the-study-of-naked-mole-rats/

Any mechanism that appears common to all cancers, or even just a wide range of cancers, is worth examination to see if it might serve as the basis for a therapy. Here is an example of speculative research of this nature:

[Researchers] have identified a gene that, when repressed in tumor cells, puts a halt to cell growth and a range of processes needed for tumors to enlarge and spread to distant sites. The researchers hope that this so-called “master regulator” gene may be the key to developing a new treatment for tumors resistant to current drugs. “This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumors studied to date. Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behavior.”

Genes in the master regulator’s family, known as high mobility group or HMG genes, [are] essential for giving stem cells their special powers, and that’s no coincidence. [Many] investigators consider cancer cells to be the evil twin of stem cells, because like stem cells, cancer cells must acquire special properties to enable the tumor to grow and metastasize or spread to different sites.

[Researchers applied techniques to block the HMGA1 gene] to several strains of human breast cancer cells in the laboratory, including the so-called triple negative cells – those that lack hormone receptors or HER2 gene amplification. Triple-negative breast cancer cells tend to behave aggressively and do not respond to many of our most effective breast cancer therapies. The team [found] that the cells with suppressed HMGA1 grow very slowly and fail to migrate or invade new territory like their HMGA1-expressing cousins. The team next implanted tumor cells into mice to see how the cells would behave. The tumors with HMGA1 grew and spread to other areas, such as the lungs, while those with blocked HMGA1 did not grow well in the breast tissue or spread to distant sites.

Link: http://www.hopkinsmedicine.org/news/media/releases/making_cancer_less_cancerous

Source:
http://www.fightaging.org/archives/2013/05/hmga1-as-a-potential-common-mechanism-in-cancer.php

Source:
http://www.longevitymedicine.tv/hmga1-as-a-potential-common-mechanism-in-cancer/

The immune system malfunctions with age, producing harmful chronic inflammation while failing to adequately respond to pathogens and failing to destroy potentially cancerous and senescent cells. Characteristic changes in immune cell populations accompany these changes, and in past years researchers have shown that adjusting these populations by destroying some of the unwanted immune cells can reverse at least some immune system declines.

Here is an open access paper that focuses on changes in the population of regulatory T cells with aging. These are cells involved in suppressing the immune response, for example so as to prevent the immune system from attacking healthy tissues:

Over the course of the human life, age-related diseases develop because of the failure of genetic traits to remain beneficial, as they were in younger years when they aided in successful reproduction. Longevity is correlated with optimal natural immunity. Immunosenescence (aging of the immune system) is continuously influenced by chronic antigenic stimulation, such as infections. This explains why the probability of a long lifespan is improved in an environment of reduced pathogen burden. In the presence of low pathogen burden one can expect a balanced state of immune responses and alter the chances of having advanced inflammatory responses

Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells.

The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in [peripheral T-regulatory cells]. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616810/

Source:
http://www.fightaging.org/archives/2013/05/t-regulatory-cells-more-numerous-in-the-aged-immune-system.php

Source:
http://www.longevitymedicine.tv/t-regulatory-cells-more-numerous-in-the-aged-immune-system/

Immunotherapy is a very broad and active field: there are a great many strategies presently under development, and in various stages of maturity. All aim at making the immune system do the heavy lifting of finding and destroying specific unwanted cells, cellular machinery, and other biochemicals in the body. This is actually the immune system's evolved purpose, more or less, and so adjusting it to destroy new targets without causing harmful side-effects is a plausible near term technology. Thus there are large segments of the life science community looking into immunotherapies for cancer, immunotherapies to destroy some of the harmful aggregates that build up between cells with age, and so forth.

One of the presentations given at last year's SENS5 conference was a look at turning the immune system against harmful aggregates of tau protein - as seen in Alzheimer's disease, for example, but which happens in all brains to some degree:

One of the perils of aging is the accumulation of various protein/peptide aggregates throughout the body, some of which are associated with toxicity. In several age-related disorders, aggregates of certain amino acid sequences are much more prominent than under normal conditions, and define the disease. Harnessing the immune system has emerged in recent years as a promising approach to treat these conditions. My laboratory has worked in this field targeting the amyloid-? peptide, the prion protein, the tau protein, and more recently the islet amyloid polypeptide. The focus of my talk will be on our tau immunotherapy studies. We have shown in tangle mouse models that active or passive immunizations clear pathological tau aggregates from the brain with associated functional benefits.

A thought to leave you with: the more we see the research community working on immunotherapies for age-related conditions, there more likely it becomes that significant investments will be made into reversing the decline of the immune system. The effectiveness of these therapies to a degree depends on the effectiveness of the immune system, and that progressively fails with age - having first generation therapies in the market will ensure that there exists a strong incentive to improve those therapies, and one of the most obvious ways to do that is to rejuvenate the immune system in elderly patients.

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