Australian researchers make a splash in the fountain of youth

Source:Xinhua Published: 2013-12-20 10:29:07

Researchers at the University of New South Wales have unlocked a hidden pathway that could hold the secrets to reversing one of life's little problems mortality and the results, published Friday, in the journal Cell could provide an entirely new arsenal against modern disease.

Researchers, led by maverick US Medical scientist David Sinclair, a consultant with Cohbar, HorizonScience, Segterra, MetroBiotech and GlaxoSmithKlineh, found a cause of aging in animals that can be blocked or reversed.

The work potentially paves the way for new treatments for age- related diseases including cancer, type 2 diabetes, muscle wasting and inflammatory diseases.

So confident of the breakthrough, Professor David Sinclair recently co-founded Metrobiotech to analyze the compound beginning with human trials late next year.

The study focuses on mitochondria - our cells' battery packs which give energy to carry out key biological functions.

Sinclair found a series of molecular events enable communication inside cells between the mitochondria and the nucleus.

As communication breaks down, aging accelerates.

"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," Sinclair, who is based at Harvard Medical School said.

"And just like a couple, restoring communication solved the problem," says the geneticist.

The background to the research is that as people age, levels of the chemical NAD, which starts this communication cascade, decline. Until now, the only way to slow the NAD drop was to restrict calories and exercise intensively.

In this work, the researchers used a compound that cells transform into NAD to repair the broken network and rapidly restore communication and mitochondrial function.

It mimics the effects of diet and exercise.

While Professor Sinclair's group in Boston was working on muscles in tissue culture, colleagues at US in Sydney were working on animal models to prove the work could have the same results.

"It was shocking how quickly it happened," says co-author Dr Nigel Turner, an ARC Future Fellow from US's Department of Pharmacology.

"If the compound is administered early enough in the aging process, in just a week, the muscles of the older mice were indistinguishable from the younger animals."

The mice, which were two years old, also performed well on insulin resistance and inflammation both of which are correlated with aging.

They were compared with six-month-old animals.

"It was a very pronounced effect," says Dr Turner. "It's something like a 60-year-old being similar to a 20-year-old on some measures."

The younger mice given the same compound were "supercharged above normal level" on certain measures, according to Dr Turner.

"So it is possible this would have benefits in healthy, young humans."

One particularly important aspect of this research involves HIF- 1, which is an intrusive molecule that foils communication, but also has a role in cancer.

It has been known for some time that HIF-1 is switched on in many cancers, now this research has found it also switches on during aging.

"We become cancer-like in our aging process," says Professor Sinclair. "Nobody has linked cancer and aging like this before." This may explain why the greatest risk of cancer is age.

The researchers are now looking at the longer-term outcomes the NAD-producing compound has on mice. They are exploring whether it can be used to safely treat rare mitochondrial diseases and other conditions, such as type 1 and type 2 diabetes, as well as for longevity and good health.

Professor Sinclair and his group have been studying the fundamental science of aging for many years, primarily focusing on a group of genes called sirtuins.

Previous studies from his lab had shown that one of these genes, SIRT1, was activated by the naturally occurring compound resveratrol (found in small amounts in grapes, red wine and certain nuts).

The latest research goes further, as it activates all seven of the sirtuin genes.

"There's clearly much more work to be done here, but if those results stand, then aging may be a reversible condition, if it is caught early," Professor Sinclair said.

Posted in: Biology

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