September 20, 2007 / 5:02 PM / 12 years ago

U.S. study finds potential new ways to fight aging

WASHINGTON (Reuters) - Researchers said on Thursday they had found more ways to activate the body’s own anti-aging defenses — perhaps with a pill that could fight multiple diseases at once.

An elderly man takes a stroll in a file photo. Researchers said on Thursday they had found more ways to activate the body's own anti-aging defenses -- perhaps with a pill that could fight multiple diseases at once. REUTERS/Kirsten Neumann/Files

Their study, published in the journal Cell, helps explain why animals fed very low-calorie diets live longer, but it also offers new ways to try to replicate the effects of these diets using a pill instead of hunger, the researchers said.

“What we are talking about is potentially having one pill that prevents and even cures many diseases at once,” said David Sinclair, a pathologist at Harvard Medical School who helped lead the research.

Sinclair helped found a company that is working on drugs based on this research, Sirtris Pharmaceuticals.

The key is a family of enzymes called sirtuins. They are controlled by genes called SIRT1, SIRT2 and so on.

Last year, researchers showed that stimulating SIRT1 can help yeast cells live longer.

Sinclair, working with colleagues at his company, at Cornell University in New York and the U.S. National Institutes of Health, identified the actions of two more sirtuin genes called SIRT3 and SIRT4.

They found the enzymes controlled by these genes help preserve the mitochondria — little organs inside of cells that provide their energy.

“These two genes, SIRT3 and SIRT4, they make proteins that go into mitochondria. ... These are little energy packs inside our cells that are very important for staying healthy and youthful and, as we age, we lose them and they get less efficient,” Sinclair said in a videotaped statement.


“They are also very important for keeping the cells healthy and alive when they undergo stress and DNA damage, as we undergo every day during the aging process.”

Sinclair and colleagues have found in other studies that even if the rest of a cell is destroyed — the nucleus and other parts — it can still function if the mitochondria are alive.

His team found that fasting raises levels of another protein called NAD. This, in turn, activates SIRT3 and SIRT4 in the mitochondria of the cell and these help keep the mitochondria youthful.

“We’ve reason to believe now that these two genes may be potential drug targets for diseases associated with aging,” Sinclair said.

“Theoretically, we can envision a small molecule (pill) that can increase levels of NAD, or SIRT3 and SIRT4 directly, in the mitochondria. Such a molecule could be used for many age-related diseases,” he added.

“Diseases like heart disease, cancer, osteoporosis — even things like cataracts. What we are aiming to do is to find the body’s natural processes that can slow down aging and treat these diseases.”

Sirtris is already working on such drugs. It has an experimental pill called SRT501, which it is testing in Phase 2a trials in patients with type-2 diabetes.

“These exciting new data further validate sirtuins as attractive targets for drug development to treat diseases of aging,” Dr. Christoph Westphal, chief executive officer of Sirtris, said in a statement.

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