What Does Life-Extending Drug Mean for Humans?

  • Share
  • Read Later

A natural compound used as an immunosuppressant in organ-transplant patients has been found to extend life in mice, according to a study published on July 8 in the journal Nature. Aging mice that were given the substance, rapamycin, lived significantly longer than mice that didn't get the drug: females that received rapamycin were 13% older at death and males 9% older.

The research, conducted as part of the National Institute of Aging Interventions Testing Program, took place at three separate test sites and involved nearly 2,000 genetically similar mice. Trials began when mice were about 600 days old — well into middle age, at a stage roughly equivalent to 60-year-old humans.

Because of their late start (researchers had intended to study mice from early ages but were stymied by technical difficulties), scientists weren't sure they could expect clear results. However, even administered late in life, rapamycin delayed the deaths of the longest-lived male mice by 101 days and by 151 days in the longest-lived females — the equivalent of about 13 years on average in humans — compared with mice with no treatment. In terms of life expectancy when treatment began (or average remaining lifespan when the mice were 600 days old), that translates to an increase of 38% in female mice and 28% in males.

Although the results are untested in humans, they do suggest that aging could be slowed by drugs. Exactly how rapamycin works is "still an open question," says Randy Strong, a pharmacology professor at the University of Texas Health Science Center at San Antonio and one of three lead authors of the study. But he and his colleagues were prompted to test the aging effects of rapamycin, which was discovered in Easter Island soil samples about 40 years ago, after noting that the compound appeared to affect cell growth in lab animals in much the same way as calorie-restricted diets, which also appear to extend life.

Scientists think rapamycin's cellular target — called mTOR for "mammalian target of rapamycin" — helps regulate the body's response to nutrients and may also, according to Strong, "gear up responses to stress," such as the oxidative stress that damages proteins and DNA and contributes to disease development. "What we're doing with rapamycin," Strong says, "is we're actually tricking the cells into thinking that they're depleted of nutrients. Rather than the animals losing weight — we haven't noticed any weight loss — they may be just using their proteins more efficiently, and then repairing proteins more efficiently."

It's this cellular efficiency, perhaps, that delays aging and helps preserve animals' good health. The findings suggest that rapamycin does not affect or prevent any one disease specifically — the mice in the study died of various causes, with no real difference between mice that received rapamycin and those that didn't — but rather that it slows aging overall.

Rapamycin's life-extending effect has been demonstrated by other researchers in past studies of worms, fruit flies and yeast; the drug appears to interfere with a similar cellular process in those species too. "I think this is a big leap from those invertebrate species to mammals," says Strong, who is also a senior research scientist for the Department of Veteran Affairs. "This gives us a good idea that perhaps it would work in humans too."

Earlier human trials have shown, however, that rapamycin can have serious side effects. Because it is an immunosuppressant, it can make users susceptible to opportunistic infections. It has also been linked to hyperlipidemia, or high levels of triglycerides in the blood, which can lead to heart disease. It's unclear whether these problems would counteract any longevity benefit that rapamycin might provide in humans. Says Strong, "I think more immediately, people are starting to look at [rapamycin] for age-related diseases like Alzheimer's disease, Parkinson's disease or kidney disease." The drug has also recently entered clinical trials as a human cancer treatment, while another study published last year showed that it may reverse mental retardation caused by the genetic disease tuberous sclerosis in mice.

As agents for extending life, other drugs may be further along in the pipeline — resveratrol, for one, which has also prolonged life in lab mice. But the new finding by Strong and his colleagues "more clearly identifies the [target of rapamycin] pathway as important across species." It may guide researchers to target different proteins in the same pathway. "If those proteins react the same way to extend lifespan, then we might be able to get rid of unwanted side effects," says Strong.