Anti-Aging  

Scientists in Japan and the United States plan to begin a joint clinical study in Japan to test the safety and effectiveness in humans of the compound NMN, that is gradually being proved to retard the aging process in animals.

Researchers at Keio University in Japan and Washington University in St. Louis are planning to begin a joint clinical study in Japan to test in humans the safety and effectiveness of a compound that is on the verge of being a proven to reverse the effects of aging. The clinical study is scheduled to begin as early as next month.

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David Sinclair was formerly associated with research of the compound, nicotinamide mononucleotide, or NMN.  Sinclair has previously said the compound could lead to breakthroughs that could be used to develop drugs to restore youthfulness in human cells.

"We've confirmed a remarkable effect in the experiment using mice, but it's not clear yet how much [the compound] will affect humans"

NMN is a chemical compound produced within the bodies of many living things, including people. NMN is also contained in food products. An experiment using mice is gradually showing that this compound activates sirtuin, whose functions are weakened due to aging, improving such things as symptoms of diabetes

Now, Keio University's Research Ethics Committee will check the appropriateness of the plan and other factors. If approved, researchers plan to begin giving the NMN to about 10 healthy people to confirm its safety. They will then examine whether NMN can improve functions of the human body.

A research group including Professor Shinichiro Imai of Washington University, a gerontology expert, has confirmed that NMN activates sirtuin. An experiment giving NMN to mice found that the compound can reverse age-linked declines in metabolism and eyesight.

Imai has been studying molecular mechanisms of mammalian aging and longevity at cellular and organismal levels for decades and making significant contributions to the field of aging research. A video profile of Imai, who is working towards the Palo Alto Longevity Prize as well, is embedded below.

The study is planned to be conducted by researchers including Imai and Keio University, using NMN made by a Japanese producer. The central government has decided to provide full-fledged support for anti-aging studies from next fiscal year, and is also paying attention to this clinical study.

"We've confirmed a remarkable effect in the experiment using mice, but it's not clear yet how much [the compound] will affect humans," Imai said. "We'll carefully conduct the study, which I hope will result in important findings originating in Japan."

SOURCE  The Japan News

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 Aging  

Researchers hope an anti-ageing compound could be tested on humans as early as next year, following a key breakthrough that saw the ageing process reversed in mice. The study, led by researcher David Sinclair, discovered a way of restoring the efficiency of cells, completely reversing the ageing process in muscles.

Researchers have discovered a cause of aging in mammals that may be reversible.

The essence of this finding is a series of molecular events that enable communication inside cells between the nucleus and mitochondria. As communication breaks down, aging accelerates. By administering a molecule naturally produced by the human body, scientists restored the communication network in older mice. Subsequent tissue samples showed key biological hallmarks that were comparable to those of much younger animals.

In tests, two-year-old mice were given a compound over a week, moving back the key indicators of ageing to that of a six-month-old mouse. Researchers said this was the equivalent of making a 60-year-old person feel like a 20-year-old.

“The aging process we discovered is like a married couple—when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down,” said Harvard Medical School Professor of Genetics David Sinclair, senior author on the study. “And just like with a couple, restoring communication solved the problem.”

This study was a joint project between Harvard Medical School, the National Institute on Aging, and the University of New South Wales, Sydney, Australia, where Sinclair also holds a position.

The study was published in the journal Cell.

Mitochondria are often referred to as the cell's "powerhouse," generating chemical energy to carry out essential biological functions. These self-contained organelles, which live inside our cells and house their own small genomes, have long been identified as key biological players in aging. As they become increasingly dysfunctional overtime, many age-related conditions such as Alzheimer’s disease and diabetes gradually set in.

Researchers have generally been skeptical of the idea that aging can be reversed, due mainly to the prevailing theory that age-related ills are the result of mutations in mitochondrial DNA—and mutations cannot be reversed.

Sinclair and his group have been studying the fundamental science of aging—which is broadly defined as the gradual decline in function with time—for many years, primarily focusing on a group of genes called sirtuins.

Previous studies from his lab showed that one of these genes, SIRT1, was activated by the compound resveratrol, which is found in grapes, red wine and certain nuts.

Ana Gomes, a postdoctoral scientist in the Sinclair lab, had been studying mice in which this SIRT1 gene had been removed. While they accurately predicted that these mice would show signs of aging, including mitochondrial dysfunction, the researchers were surprised to find that most mitochondrial proteins coming from the cell’s nucleus were at normal levels; only those encoded by the mitochondrial genome were reduced.

Image Source - Ana Gomes

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“This was at odds with what the literature suggested,” said Gomes. As Gomes and her colleagues investigated potential causes for this, they discovered an intricate cascade of events that begins with a chemical called NAD and concludes with a key molecule that shuttles information and coordinates activities between the cell’s nuclear genome and the mitochondrial genome.

Cells stay healthy as long as coordination between the genomes remains fluid. SIRT1’s role is intermediary, akin to a security guard; it assures that a meddlesome molecule called HIF-1 does not interfere with communication.

For reasons still unclear, as we age, levels of the initial chemical NAD decline. Without sufficient NAD, SIRT1 loses its ability to keep tabs on HIF-1. Levels of HIF-1 escalate and begin wreaking havoc on the otherwise smooth cross-genome communication. Over time, the research team found, this loss of communication reduces the cell's ability to make energy, and signs of aging and disease become apparent.

“This particular component of the aging process had never before been described,” said Gomes.

While the breakdown of this process causes a rapid decline in mitochondrial function, other signs of aging take longer to occur. Gomes found that by administering an endogenous compound that cells transform into NAD, she could repair the broken network and rapidly restore communication and mitochondrial function. If the compound was given early enough—prior to excessive mutation accumulation—within days, some aspects of the aging process could be reversed.

When Sirt1 loses its ability to monitor HIF-1, communication between mitochondria and the nucleus breaks down, and aging accelerates. Image by Ana Gomes

Examining muscle from two-year-old mice that had been given the NAD-producing compound for just one week, the researchers looked for indicators of insulin resistance, inflammation and muscle wasting. In all three instances, tissue from the mice resembled that of six-month-old mice.

One particularly important aspect of this finding involvesHIF-1. More than just an intrusive molecule that foils communication, HIF-1 normally switches on when the body is deprived of oxygen. Otherwise, it remains silent. Cancer, however, is known to activate and hijack HIF-1. Researchers have been investigating the precise role HIF-1 plays in cancer growth.

“It’s certainly significant to find that a molecule that switches on in many cancers also switches on during aging,” said Gomes. “We're starting to see now that the physiology of cancer is in certain ways similar to the physiology of aging. Perhaps this can explain why the greatest risk of cancer is age.”

“There’s clearly much more work to be done here, but if these results stand, then certain aspects of aging may be reversible if caught early,” said Sinclair.

The researchers are now looking at the longer-term outcomes of the NAD-producing compound in mice and how it affects the mouse as a whole. They are also exploring whether the compound can be used to safely treat rare mitochondrial diseases or more common diseases such as Type 1 and Type 2 diabetes. Longer term, Sinclair plans to test if the compound will give mice a healthier, longer life.



SOURCE  Harvard Medical School

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 Aging  

David Sinclair has been working on a cure for aging since the 1990's.  His work with resveratrol and the sirtuin genes may one day lead to medicines that delay the onset of aging.

Can we really cure ageing? David Sinclair thinks so, and he's going to try to prove it.

In the TEDx talk above, Sinclair talks about his personal experiences with aging, and why he decided to do something about it.

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His research is aimed at understanding why we grow old and using this knowledge to prevent and treat both rare and common diseases. He is perhaps best known for identifying resveratrol from red wine as an anti-aging molecule.

Sinclair has also worked on research to redefine what aging is. Previously aging was thought to be brought about by accumulating genetic mutations in our cells.  Now, it has been shown that the process may be the result (or at least partially the result of) of a buildup of chemicals that turn certain genes on.  This epigenetic change may be reversible.

He has founded four biotechnology companies; to treat age-related diseases (Sirtris), improve female reproductive health and IVF (OvaScience), treat type 2 diabetes (Cohbar), and develop vaccines against malaria, chlamydia, tuberculosis, pneumonia, and cancer (Genocea).

Sinclair is a scientist and entrepreneur working on increasing human health, productivity, and lifespan. After co-discovering a molecular cause of aging at the Massachusetts Institute in Boston in the mid-1990s, he joined the faculty of Harvard Medical School where he is now a tenured Professor. In 2005, he founded the Glenn Laboratories for Aging Research at Harvard and serves as their Co-Director. He is also a Professor at the Lowy Cancer Centre at the University of New South Wales, Sydney.




SOURCE  TEDx Talks

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 Anti-Aging  

Resveratrol-based drugs that combat aging may be available within five years says the discoverer of the Sirituin activating compounds, David Sinclair. In a recently published paper, the researcher and his team foudn that a whole new class of anti-aging drugs is now viable by targeting the enzyme SIRT1.

According to a prominent Australian researcher, drugs that combat aging may be available within five years, following landmark research.

The study, published in a recent issue of the journal Science, finally proves that a single anti-aging enzyme in the body can be targeted, with the potential to prevent age-related diseases and extend lifespans.

The paper shows all of the 117 drugs tested work on the single enzyme through a common mechanism. This means that a whole new class of anti-aging drugs is now viable, which could ultimately prevent cancer, Alzheimer's disease and type 2 diabetes.

"Ultimately, these drugs would treat one disease, but unlike drugs of today, they would prevent 20 others," says the lead author of the paper, Professor David Sinclair, from UNSW Medicine, who is based at Harvard University. "In effect, they would slow aging."

The target enzyme, Sirtuin 1 (SIRT1), is switched on naturally by caloric restriction and exercise, but it can also be enhanced through activators. The most common naturally-occurring activator is resveratrol, which is found in small quantities in red wine, but synthetic activators with much stronger activity are already being developed.

Professor David Sinclair

Although research surrounding resveratrol has been going for a decade, until now the basic science had been contested. Despite this, there have already been promising results in some trials with implications for cancer, cardiovascular disease and cardiac failure, type 2 diabetes, Alzheimer's and Parkinson's diseases, fatty liver disease, cataracts, osteoporosis, muscle wasting, sleep disorders and inflammatory diseases such as psoriasis, arthritis and colitis (inflammatory bowel disease).

"In the history of pharmaceuticals, there has never been a drug that tweaks an enzyme to make it run faster," says Professor Sinclair, a geneticist with the Department of Pharmacology at UNSW.

The technology was sold to pharmaceutical giant GlaxoSmithKline in 2008 for over $700 million. Four thousand synthetic activators, which are 100 times as potent as a single glass of red wine, have been developed -- the best three are in human trials.

"Our drugs can mimic the benefits of diet and exercise, but there is no impact on weight," says Professor Sinclair, who suggests the first therapeutic to be marketed will be for diabetes.

There have been limited trials in people with type 2 diabetes and the skin inflammatory disease, psoriasis. There were benefits to the metabolism in the first group and a reduction in skin redness in the second.

The drugs can be administered orally, or topically. So far, there have been no drugs developed targeting aging skin, but one major skin care range has developed a crème with resveratrol in it.

While any drug would be strictly prescribed for certain conditions, Professor Sinclair suggests that one day, they could be taken orally as a preventative. This would be in much the same way as statin drugs are commonly prescribed to prevent, instead of simply treating, cardiovascular disease.

In animal models, overweight mice given synthetic resveratrol were able to run twice as far as slim mice and they lived 15 per cent longer.

"Now we are looking at whether there are benefits for those who are already healthy. Things there are also looking promising," says Professor Sinclair, who also heads the Lowy Cancer Research Centre's Laboratory for aging Research at UNSW.

"We're finding that aging isn't the irreversible affliction that we thought it was," he says. "Some of us could live to 150, but we won't get there without more research."

Sinclair is featured in the BBC Horizon episode on reversing aging below:




SOURCE  University of New South Wales

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