Short telomeres, the culprit in all of these rare genetic diseases of aging, have also been linked to more common disorders of old age. Richard Cawthon, a geneticist at the University of Utah, has developed a way to measure telomere length in human white blood cells, and in one study, reported in the journal Lancet, he examined DNA samples from people age 60 and older that had been taken 15 to 20 years earlier. Then he researched medical and death records to look for a correlation between telomere length and mortality. Elderly people who originally had the shortest telomeres had three times the number of deaths from heart disease, eight times the deaths from infectious diseases and higher overall mortality than people with the longest telomeres. (Cawthon and his colleagues didn’t have enough data to follow cancer risk, though that’s now being examined in a follow-up study.) “We can’t say whether short telomeres are a cause or consequence of these differences in morbidity and mortality or simply an indicator of risk,” Cawthon says. “Perhaps having to fight off more diseases shortens telomeres in immune cells more quickly. Or it could be the opposite—that having short telomeres gives you more diseases.”
But another study, by Cawthon, Blackburn and Elissa Epel, a health psychologist at the University of California, San Francisco, found evidence that life stresses can shorten telomeres and reduce telomerase. In this study, they compared women supporting a chronically ill child with a control group of women. The researchers measured the women’s stress levels through questionnaires asking how long they had been caring for their sick child and their perceptions of stress. They also tested urine for a biochemical marker, F2-isoprostane, that measures oxidative stress (the production of harmful molecules called free radicals). Those with the highest, longest-lasting stress, regardless of whether they had a sick child, proved to have shorter-than-normal telomeres, lower levels of telomerase and more oxidative stress.
“We might speculate that it’s the stress that causes shorter telomeres,” Cawthon says. Although he didn’t look at the prevalence of disease, it’s known that stress is an important risk factor for the types of diseases seen in the people with short telomeres in the earlier study. A follow-up study will look at possible connections between stress-induced short telomeres and common diseases of aging.
Other environmental factors might either weaken telomerase or shorten telomeres, influencing when pathologies of aging ensue and what tissues they affect. For example, Greider observes that patients who smoke get pulmonary fibrosis 10 to 20 years earlier than they otherwise would, probably because lung cells must constantly repair damage from smoke. Regardless of the cause and effect, though, short telomeres could be useful in predicting reduced longevity or poor health. Physicians someday might benefit from knowing their patients’ telomere lengths along with other risk factors.
The news that telomere shortening is a normal part of getting old but is exacerbated in age-linked diseases has captured the imagination of biotech and cosmetic companies. Many products— including TA-65 marketed by TA Sciences, which collaborates with Geron, and cosmetic creams advertising an “enzyme therapy” that can “reset your cell’s aging clock”—already claim to reverse the effects of aging by reactivating telomerase, though none of these products is based on research published in peer-reviewed journals. Some therapies are being promoted as “nutriceuticals” from natural products and thus don’t require FDA approval, Campisi says.
In published studies, research on the telomere link between cancer and aging is still in the early stages—and fraught with the paradoxes inherent in telomeres. For example, Maria Blasco at the Spanish National Cancer Center in Madrid elevated the telomerase in skin and hair follicles of mice. These mice had healthier skin, better wound healing and more luxuriant fur. The downside was a higher rate of skin cancer.
But because skin infections are a huge health problem for the elderly and bedridden, and because cancers often take years to develop, the benefits of an ointment that helps wounds heal might be worth the tradeoff for some patients. Likewise, the theoretical risk of cancer might not matter much to patients with dyskeratosis congenita, aplastic anemia or pulmonary fibrosis. These trade-offs boil down to the fact that there are two types of diseases of aging. One kind—encompassing heart failure, skin deterioration and immune system collapse—comes from decreased cell renewal in which telomere shortening triggers cell death. The other—cancer—comes from increased cell proliferation made possible by the restoration of telomeres, which is often attributable to telomerase reactivation.
The upshot, at least for now, is that although we may eventually be able to slow or reverse the ravages of age, it could come at the cost of increased cancer risk. And although we could be closer to finding a way to inhibit tumor growth by blocking telomerase, such therapies might carry their own risks and are likely still years away. But whatever the ultimate results, today’s research on telomeres and telomerase is expanding our knowledge of how biology works. By understanding what happens when telomeres shorten too quickly or telomerase activity levels are out of whack, we can appreciate the intricate, interlocking measures that keep us healthy not only for our reproductive life but also for many years beyond—long enough that we have the luxury to worry about things as trivial as wrinkles and gray hair. 
 Dossier
1. “Telomeres and Telomerase: The Path From Maize, Tetrahymena and Yeast to Human Cancer and Aging,” by Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak, Nature Medicine, October 2006. The recipients of the 2006 Albert Lasker Basic Medical Research Award describe the interdisciplinary collaboration that led to the discovery of the structure of telomeres and the enzyme telomerase.
2. “The Common Biology of Cancer and Aging,” by Toren Finkel, Manuel Serrano and Maria Blasco, Nature Reviews, August 2007. A detailed review of research into how telomeres and telomerase underlie the biology of both cancer (a problem of uncontrolled cell division) and aging (one of cell senescence).
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