Aging Reversed In Mice: Is Immortality Next?
November 30, 2010
Movie audiences thought it was a gripping fantasy when Brad Pitt aged backwards in the Curious Case of Benjamin Button. But now a study by geneticist Ronald DePinho suggests that aging really can be reversed by reactivating an enzyme that protects the tips of chromosomes.
Call it The Curious Case of Telomerase.
Mice engineered to lack the enzyme telomerase become prematurely decrepit: barely fertile and suffering from age-related conditions such as osteoporosis, diabetes and neurodegeneration.
But when telomerase was switched back on, shriveled testes grew back to normal, the abnormal animals regained fertility, and organs, such as the spleen, liver, and intestines, were rejuvenated and they grew larger brains with more neural activity, report researchers at Dana-Farber Cancer Institute and Harvard Medical School in Boston.
“What really caught us by surprise was the dramatic reversal of the effects we saw in these animals,” says senior author Dr. Ronald A. 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.
The finding, published online today in Nature1, 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 DePinho. He says that the study indicates that there is a “point of return” in aging, adding, “This has implications for thinking about telomerase as a serious anti-aging intervention.”
Other scientists caution that mice lacking telomerase are a poor stand-in for the normal ageing process. And in humans, they say, ramping up telomerase could encourage the growth of tumours.
Since its discovery in the 1980s, telomerase has been heralded as a potential fountain of youth.
Here’s how it works: Chromosomes have caps of repetitive DNA called telomeres at their ends. Every time cells divide, their telomeres shorten, which eventually prompts them to stop dividing and die. Telomerase prevents this decline in some kinds of cells, including stem cells, by lengthening telomeres, and the hope was that activating the enzyme could slow cellular aging.
Researchers now realize that the role of telomerase in aging is complex than first thought. Some studies have uncovered an association between short telomeres and early death, whereas others have failed to back up this link. People with rare diseases characterized by shortened telomeres or telomerase mutations seem to age prematurely, although some tissues are more affected than others.
DePinho’s team genetically engineered mice with inactivated telomerase that 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.
Mice with restored telomerase activity had noticeably larger brains than animals still 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 ageing, he says, and perhaps even for more common age-related conditions.
He says he recognizes that there is more to ageing 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 ageing. “This may be one of several things you need to do in order to extend lifespan and extend healthy living,” he says.
Happy Birthday Alice Herz-Sommer, 107, Oldest Holocaust Survivor
November 26, 2010
A couple of weeks ago, I posted a 12-minute trailer for “Dancing Under the Gallows”, a film about pianist Alice Herz-Sommer, the oldest living Holocaust survivor. Her astonishing spirit captivated tens of thousands of viewers.
Many have written to express their disappointment that the original trailer has been removed from the web. I’m sorry, but that’s out of my control. Below is a shorter, still amazing look at Alice in her London flat.