The Cure for Aging

by Laura Carstensen,

A drug from dirt and Siamese mice have researchers inching toward the seemingly impossible

If there were Guinness World Records dedicated to high-achieving rodents, Mouse UT2598 would deserve a mention. The average life span for a mouse is 2.3 years–so at age 3 and still going strong, Mouse UT2598 has a shot at beating the record for longest-lived, which stands at about 4. Translating that to a human life span, he’s hovering around the centennial mark, but on the outside, he looks no different from his much younger brethren. His fur is glossy black, he’s lean, and while he’s a bit on the small side, he’s scrappy and surprisingly active as he explores, sniffs and pokes around his cage at the University of

What gives Mouse UT2598 his edge is a compound called rapamycin, which seems to slow aging and the damage it can do, at least to certain cells. His liver and heart function as if they were far younger, and his tendons have more spring and flexibility than they should at his age. There’s also less evidence of tumors in his organs than is considered normal, so he could be spared the effects of cancer for quite a while longer. Place him alongside other mice his age, and the contrast is unmistakable.

Nobody is talking about living forever. But as these experts see it, aging is the single most powerful factor in the diseases that are most likely to cut our lives short: cancer, heart problems, immune disorders and degenerative brain conditions like Alzheimer’s.

Mouse UT2598’s longevity diet laced with rapamycin traces its existence back to some dirt samples collected in 1964 on an expedition to Easter Island. Those soil samples became the basis for developing a new antibiotic, which was named rapamycin. Researchers noticed that mice that were given the drug tended to live longer–by about 20%, compared with those that weren’t taking it.

“Rapamycin is neat because it works in a wide variety of species, from yeast, worms and flies to mice,” says David Harrison.

t turns out that rapamycin interrupts the function of a gene called mTOR, found in both mouse and man, which acts as a traffic signal for directing how cells take in and use energy. If there’s plenty to eat, the gene is busy greenlighting cells to absorb nutrients and grow, grow, grow. When food gets scarce, the gene goes quiet, halting the cell-growing machinery until the next feeding time.

The more active state–the one in which cells are processing nutrients and growing–turns out to age cells considerably: as our cells are working hard to process our food, they also spew out toxic free radicals. The goal, then, is to keep mTOR as subdued as possible, preferably without requiring animals to starve themselves miserable. And that’s what rapamycin appears to do.

Human patients who took the drug after kidney transplants to lower their chances of rejecting the organ, for instance, also had slightly higher chances of developing diabetes, and the risk of cataracts requires more study before a broad application of the drug would be possible.

For other researchers, the key to longevity may be in our genes. Telomeres are the timekeepers of a cell’s life; each time a cell divides, it copies its chromosomes’ DNA, and like a knot tied at the end of a thread, telomeres signal the end of the copying process. With each cell division, these little squiggles, which are the final segments of DNA at the ends of chromosomes, shorten–eventually disappearing altogether.

what’s happening in these labs is not just about extending a life indefinitely but rather extending a healthy life for a little bit longer. And researchers say they’re truly optimistic that breakthroughs will come in their lifetime. After all, says Harrison, “It must not be all that complicated, or we wouldn’t be having the success that we’re having.”

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