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Aging, Chronic Disease and Telomeres Are Linked in Recent Studies

By Jeffrey Norris, UCSF Public Affairs | February 4, 2011

Those of us with many birthdays under our belts may look spry on some days and appear haggard on others, but is there any gauge for how well we really are aging within?

Elizabeth Blackburn, PhD, is not ready to predict how long you will live. But she and her UCSF colleagues are exploring a feature within cells that is a kind of hourglass. While the hourglass appears to mark cellular aging, she says that we may also be able to turn it upside down.

Within cells, it’s not sand, but rather DNA that is gradually slipping away. The DNA hourglass runs at different rates for different people. Sometimes it runs at different rates within the same individual at different times. And surprisingly, in some cells, in some people, this hourglass may defy time for a spell, running backward with the aid of a key enzyme.

Blackburn is optimistic that we may derive health benefits from medical tests and, perhaps, treatments based on discoveries stemming from this bit of DNA – called the telomere – and the enzyme that acts on it.

Telomeres are appended to the ends of all 46 chromosomes in all of our cells. Once telomeres become too short, cells can no longer multiply to replenish body tissues. The progressive shortening of this chromosome-capping, protective bit of DNA now appears to be associated with risk for certain chronic diseases. Studies even show that people with longer telomeres are more likely to live longer and, arguably even more significantly, to have more years of healthy life.

Already, over the past decade, Blackburn’s research group and others have found links between shorter telomeres and risks for cardiovascular disease, diabetes, some cancers, depression, pulmonary fibrosis, vascular dementia, osteoarthritis and osteoporosis.

“More and more, we are thinking about how telomeres and their maintenance are involved in issues of human health,” Blackburn said during a January 4 seminar talk at UCSF’s Mission Bay campus.

Nobel Prize-Winning Line of Inquiry
Twenty-six years ago, Blackburn, who was then at UC Berkeley, and her then graduate student Carol Greider, now at Johns Hopkins University, discovered a new enzyme that they named telomerase. When active in cells, telomerase can lengthen telomeres and prevent chromosomes from being whittled down as cells repeatedly divide to replenish their numbers.

A little bit of telomerase activity may promote the health of certain types of cells. On the other hand, while the resulting longer telomeres in normal cells of the body help reduce the chances that one will get certain cancers, telomerase becomes abnormally active in well-established tumors. This superactivated telomerase helps the already aberrant tumor cells become immortal.

For their discovery of telomerase and their studies of telomeres, Blackburn and Greider shared the 2009 Nobel Prize in Physiology or Medicine with another telomere researcher and collaborator with Blackburn, Jack Szostak of Harvard Medical School.

Today, drugs that target tumor cells by blocking their abnormally high levels of telomerase already are in clinical trials. Telomeres and telomerase also remain a focus of research aimed at deepening scientific understanding of aging, stress and chronic disease.

There is even an over-the-counter telomerase activator on the market, called TA-65, licensed by T.A. Sciences from Geron. But for now, any health benefits it might provide remain unproven.

Blackburn’s University research program has broadened, and now ranges from getting at the nuts and bolts of why the status of telomeres is important at the cellular level to measuring telomere maintenance in humans and looking for new associations with disease risk.

Read more at Jeffrey Norris, UCSF Public Affairs