Reverse Aging

Premature aging can be reversed by reactivating an enzyme that protects the tips of chromosomes, as a study in mice suggests.

Mice were engineered to lack the enzyme telomerase and were shown to become prematurely decrepit. However, they bounced back to health when the enzyme was replaced. The finding, published online in “Nature”, hints that some disorders, characterized by early aging could be treated by boosting telomerase activity.

It also offers the possibility that normal human aging could be slowed by reawakening the enzyme in cells where it has stopped working, says Ronald DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, who led the new study. “This has implications for thinking about telomerase as a serious anti-aging intervention.

When mice are engineered to lack telomerase altogether, their telomeres progressively shorten over several generations. They age much faster than normal mice — they are barely fertile and suffer from age-related conditions such as osteoporosis, diabetes and neurodegeneration. They also die young. “If you look at all those data together, you walk away with the idea that the loss of telomerase could be a very important instigator of the agiing process,” says DePinho.

To find out if those dramatic effects are reversible, DePinho’s team engineered mice such that the inactivated telomerase could be switched back on by feeding the mice a chemical called 4-OHT. The researchers allowed the mice to grow to adulthood without the enzyme, then reactivated it for a month. They assessed the health of the mice another month later.

“What really caught us by surprise was the dramatic reversal of the effects we saw in these animals,” says DePinho. He describes the outcome as “a near ‘Ponce de Leon’ effect” — a reference to the Spanish explorer Juan Ponce de Leon, who went in search of the mythical Fountain of Youth.

Shriveled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver and intestines, recuperated from their degenerated state.

Telomerase also reversed effects of aging in the brain. Mice with restored telomerase activity had larger brains than animals lacking the enzyme, and neural progenitor cells, which produce new neurons and supporting brain cells, started working again.

“It gives us a sense that there’s a point of return for age-associated disorders,” says DePinho. Drugs that ramp up telomerase activity are worth pursuing as a potential treatment for rare disorders characterized by premature aging, he says, and perhaps even for more common age-related conditions.

DePinho says he recognizes that there is more to aging than shortened telomeres, particularly late in life, but argues that telomerase therapy could one day be combined with other therapies that target the biochemical pathways of aging. “This may be one of several things you need to do in order to extend lifespan and extend healthy living,” he says.

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