Samstag, 21. Februar 2015

telomeres— tiny segments of DNA that may help you live longer



Science is unlocking the anti-aging secrets of telomeres—tiny segments of DNA that may help you live longer







Calvin Harley, PhD, recently glimpsed the possible future of medicine—and maybe a forecast of his own mortality.


 It was 2010, a tumultuous year for Dr. Harley as he helped launch a start-up biotech company. "I was under a lot of stress, wasn't doing much exercise, and had gained a bit of weight," he says. In the midst of the craziness, he subjected his blood to a series of tests that measured the length of his telomeres—segments of DNA at the ends of chromosomes. 

As a pioneering researcher who began studying telomeres at McMaster University in Canada during the 1980s, he'd been among the first to undergo such testing decades ago. But advances that have recently made tests faster, cheaper, and more consistent allowed him to spot a trend: His telomeres were rapidly getting shorter.

If you don't know the significance of having short telomeres (or even what they are), you're likely to be hearing a lot more about it soon, partly due to scientists like Dr. Harley. In 1990, he and colleagues had published a groundbreaking paper in the journal Nature connecting telomere shortening to aging in human cells. 


More recently, studies have linked telomere length to an array of chronic age-related conditions, including cardiovascular disease, diabetes, osteoporosis, osteoarthritis, infections, and Parkinson's and Alzheimer's diseases, along with some forms of cancer. 

Discoveries related to telomeres, aging, and health have been so significant that one of Dr. Harley's Nature coauthors went on to share the 2009 Nobel Prize in Physiology or Medicine for her work in the field.

Knowing all this while pondering his test results, Dr. Harley decided to make some changes. He started running more and eating a healthier diet. He lost 10 pounds and eased up at work. Measuring his telomeres every 3 to 6 months since, he's noted another trend: "More recently, my telomeres have increased in length."


Such stories could become commonplace in the next 3 to 5 years—and Dr. Harley has an interest in seeing that happen. The company he cofounded, Telome Health, is one of at least three around the world—others are in Spain and Canada—that offer telomere tests. 


Right now the test is available to individuals through their doctors, but a new Telome method that uses saliva instead of blood now puts tests within reach of the general population. "Some doctors see telomere tests like a new cholesterol test," Dr. Harley says, "something you'd do on a regular basis."

But what telomere length means for any given person isn't entirely clear, and a lot of questions remain unanswered. What does the length of our telomeres really say about our health? Can lengthening them lead to longer life? How much can we control them? 


And most important, what can we do to build on breakthrough discoveries about telomeres, aging, and disease to improve our well-being and live healthier longer?




UNWINDING THE AGING CLOCK



Telomeres are like the little caps at the ends of shoelaces that prevent the laces from unraveling. In this case, they prevent rodlike chromosomes from fraying and tangling with other chromosomes. Without telomeres, genetic information would degrade, causing cells to malfunction, increasing the risk of disease, or even hastening death. Every time a cell divides, its telomeres get a little shorter. Years of replication can eventually wear telomeres down so far that cells can't divide anymore, and they become dormant or die. 


As more tissues have trouble rejuvenating, the body follows the cells, aging and eventually breaking down. In short, your cells have an aging clock built into them. But your chronological age in years doesn't set the clock—your biological age in telomere length does.

In the largest study on telomere length and health to date (it matched telomere measurements with electronic medical records and other data on more than 100,000 adults of different ages), the 10% of people with the shortest telomeres were almost 25% more likely to die in 3 years than people with longer telomeres.


 "What we don't know is whether telomere length is a passive marker of health and aging or if it actively determines things like whether you're going to be susceptible to heart disease or how long you'll live," says study leader Catherine Schaefer, PhD, director of the research program on genes, environment, and health at the Kaiser Permanente Division of Research in Oakland, CA. Either way, the association is significant.

 "Finding out you have short telomeres isn't the same as getting a death sentence," Dr. Schaefer says. "But the increase in risk is about the same as if you smoked a pack of cigarettes a day for 30 years."

In theory, if telomeres don't shorten, cells might become immortal. And research suggests a way that might happen. For most of our adult lives, telomeres seem to stay fairly stable, shortening mostly after middle age. 


However, at any given age, there is a lot of variation in telomere length between individuals. Some people's telomeres are from two to three times longer than other people's.

 Studies find that 15 to 25% of people's telomeres actually lengthen, on average, over 2 to 6 years—though not much beyond that. 

Studies suggest that when telomeres are lengthier to start, they tend to change less with time. Telomerase plays a role. This enzyme lengthens telomeres and prevents them from eroding. In fact, cells produce more telomerase to prevent the shortest telomeres from going critical. Could enough telomerase prevent cells from dying?


It stands to reason that activating telomerase might lengthen telomeres and promote better health. In a European study, mice that were genetically engineered to lack telomerase aged fast and died young. But when some of these mice had their telomerase turned back on, the effects of aging were dramatically reversed and they bounced back to health.

Nutraceutical supplements are already on the market, is purported to activate telomerase in hopes of producing similar effects. Its active ingredient is a root extract of Astragalus membranaceus, a plant often used in traditional Chinese medicine. In a 2010 study, adults averaging age 63 who took the supplement had proportionally fewer short telomeres after a year.




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Recent European research finds that when mice are genetically treated to ramp up telomerase, they lengthen their short telomeres, age more slowly, stay healthy longer, and extend their lives by as much as 24%—without getting more cancer.

"Processes that make tissues get old may be part of the same processes that protect us from tumors," says Christine Parks, PhD, an epidemiologist at the National Institute of Environmental Health Sciences. 







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