Lifegevity

Why mess with a perfectly well crafted story about living longer than you deserve?

A potential longevity-enhancing drug has passed its final animal testing challenge, pushing closer to reality the dream of all-purpose drugs against diseases of aging.

Mice given the new drug, called SRT1720, gorged on high-fat food for four months without gaining weight or developing diabetes, and ran twice as far on a treadmill as their control-group counterparts. Similar drugs are expected to follow down the pipeline.

"If you look at all the things that have fundamentally changed medicine in the last 150 years, washing hands would be one, and antibiotics another. This could be the third," said study co-author Philip Lambert, a pharmacologist at Sirtris Pharmaceuticals, the drug's developer. "If you could keep your health for another 10 or 15 years, that would be amazing."

SRT1720 activates one of several enzymes that regulate the function of mitochondria — cellular power generators that convert glucose into chemical energy. The wearing down of these generators has been linked to heart disease, Alzheimer's disease, diabetes, cancer and other age-related afflictions.

That same enzyme is also targeted by resveratrol, a naturally occurring compound that reduces age-related diseases in lab animals and is already used by longevity enthusiasts. Researchers at Sirtris showed last year that synthetic drugs that activate the enzyme produced the same cell-level changes as resveratrol, but the tests only lasted for two weeks. The latest study lasted four months, suggesting that SRT1720 — and perhaps the class of enzyme activators expected to follow — are for real.

"This shows you can make drugs that work even better than resveratrol," said David Sinclair, co-founder of Sirtris, who compared the finding to the synthesis of antibiotics inspired by early fungal components. "Now we've got human-designed synthetic molecules. We're not talking about plant extracts anymore."

Rafael de Cabo, a National Institute on Aging gerontologist who is researching SRT1720 but was not involved in the study, published today in Cell Metabolism, agreed with Sinclair's assessment, though he cautioned against premature celebration.

"From rodents to humans is a long, long process," he said. "We've demonstrated this in cells, and in mice. Now we need to move to the next level — primates or humans."

Resveratrol is currently in clinical trials as a diabetes drug, and could be joined next year by SRT1720, said Lambert.

The drug's side effects aren't yet apparent, but resveratrol has proven safe in animals and — anecdotally, at least — in humans. Since SRT1720 works at doses 1000 times lower than resveratrol, said Lambert, it should prove even safer if effective.

He noted that the blood sugar-lowering effects from SRT1720 observed in the study were present in mice on a high-fat diet, but not in mice on standard fare. This suggests that SRT1720 won't produce hypoglycemia, a dangerous dip in blood sugar that is a common side effect of diabetes treatments.

If SRT1720 and resveratrol are approved for diabetes, they will likely be used off-label to treat other diseases, from cancer to Parkinson's, that become more common with age and may involve age-related mitochondrial degeneration and the resulting metabolic disarray of key tissues and organs.

That model of disease is not yet the consensus in the medical community, which views those diseases as having multiple causes rather than a common root, and has generally ignored mitochondrial factors in its search for cures.

"The study again indicates that it's metabolic function that regulates diabetes and obesity, rather than changes in the activity of structural genes," said University of California, Irvine mitochondrial therapy pioneer Douglas Wallace, referring to genes that code for non-mitochondrial functions. "You have to look at tissue metabolism to understand the disease biology. The traditional mechanism of looking at a few nuclear gene processes is not going to be productive."

As for longevity-enhancing drugs, said Wallace, "there will be others."