October 23, 2015

Anti-aging rapamycin is being tested in 20 dogs

Scientists who study aging are currently riveted by a group of 20 dogs in Seattle. The dogs, all house pets older than six years old, are early test subjects in a trial of a drug called rapamycin. The way the drug works is not completely understood, but it’s been used for years to prevent rejection of transplanted organs, and in laboratory studies, it’s lengthened the life spans of diverse species: worms, fruit flies, and mice. If it works in dogs, healthy human volunteers will be the next guinea pigs.

Rapamycin extended mouse life spans between 9 percent and 14 percent, and it worked whether mice began getting the drug during middle age or very late in their short lives. Moreover, it prevented cardiovascular damage and memory loss. That suggests that it might lengthen the period in which people are healthy and functional rather than drawing out a period of decline.

The only other substance that has recently generated as much excitement among aging researchers is the diabetes drug metformin. It’s had only modest effects in mice but has already shown promise in humans. According to a 2014 study that followed 7,800 diabetics, those on the drug not only lived longer than other people with diabetes, they lived slightly longer than nondiabetic control subjects. Researchers believe that it’s less likely than rapamycin to have problematic side effects but also less likely to show dramatic results.

In fact, rapamycin is one of several anti-aging drugs that may end up in human trials in the coming years as researchers improve their understanding of the mechanisms of aging.

There are already some known side effects: at high doses, rapamycin can raise blood sugar and thereby increase the risk of diabetes. It causes mouth lesions known as canker sores. Researchers originally worried that because it works as part of an immune-suppressive cocktail for organ transplants, it would raise the risk of infection. But then a study last year in Science Translational Medicine showed that a derivative of the rapamycin drug seemed to enhance human immunity following a flu shot.

Scientists aren’t sure why rapamycin suppresses the immune system in some contexts and boosts it in others. But they are starting to grasp how it might slow the aging process.

Science Translational - mTOR inhibition improves immune function in the elderly

Over time cells are degraded by several factors, including damaged DNA, misfolded proteins, and excessive inflammation. This degeneration can’t be stopped altogether, but researchers have found a surprising number of ways to slow it down in yeast cells and other living things. The common thread seems to be calorie restriction. If you cut down the food supply enough, a series of biochemical changes switch the body into a kind of lower gear so it can hunker down for survival.

Rapamycin and other drugs that appear to slow aging in animals work by triggering this same biochemical pathway. The idea, says Harvard Medical School researcher David Sinclair, is to trick the body into acting as if it’s running out of energy and putting more effort into long-term survival.
S. Jay Olshansky, a professor of public health at the University of Illinois, is an outspoken critic of untested products sold to the public by what he calls the “anti-aging industry.” But he says he’s optimistic about the current work on rapamycin and another drug, a diabetes treatment called metformin. He refers to the leaders of these projects as “real scientists.”

mTOR and Human Aging

Inhibition of mTOR signaling extends life span and delays the onset of aging-related diseases in all species studied to date. These findings suggest that the mTOR pathway regulates aging. However, it is unknown if mTOR inhibition has beneficial effects on aging in humans. To begin to address this question, Mannick et al. evaluated the effects of the mTOR inhibitor RAD001 on the decline in immune function that occurs during aging in humans. Their findings suggest that RAD001 improved immune function in elderly volunteers as assessed by response to influenza vaccination. It remains to be determined whether mTOR inhibition improves additional aging-related conditions in humans.

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