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Researchers Identify Genetic Variant Linked to Faster Biological Aging

Individuals carrying the variant had shorter telomeres, stretches of DNA at the ends of chromosomes that protect them from daily wear--and also aging



Hesed M. Padilla-Nash and Thomas Ried form the National Cancer Institute

There's no right answer when someone asks you: "How old do you think I am?"

Faced with such a dilemma, most of us aim low—erring on the side of flattery rather than honesty. But the truth is, accurately guessing someone's age is a difficult task, perhaps best left to amusement park workers and street performers.

Why is it that some people just look older (or younger) than they really are? Scientists may have found the answer.

Chronological age is very different from biological age—the condition of chromosomes after each cellular division—according to Nilesh Samani of the University of Leicester, co-author of a February 7 report published in Nature Genetics. Biological age, Samani says, is related to the length of telomeres—stretches of DNA at the ends of chromosomes, which protect these precious packages of genes from daily wear and tear. We're born with telomeres of a certain length, and these get shorter as our cells divide, resulting in aging, scientists think.

But not all telomeres are born equal. Telomere length varies from person to person, but is similar in siblings, suggesting it might be under some genetic control. Samani and his colleagues analyzed more than 500,000 genetic variations (naturally occurring, single-nucleotide differences) spanning the genome in blood cells collected from almost 3,000 people. The researchers found that individuals carrying a particular genetic variant had shorter telomeres—meaning less padding for those fragile genes. The variant lies near a gene called telomerase RNA component, or TERC, and earlier studies in animals have shown that low TERC expression is associated with shorter telomeres, and faster biological aging.

The telomeres of people carrying one copy of the variant looked on average three to four years older, according to their lengths, than those of someone the same chronological age without the variant. There also was a gene dosage effect: Two copies of the variant (one inherited from each parent) resulted in an additive aging effect of six to eight years—meaning that a 50-year-old carrying two copies of the variant had the telomeres of someone aged 58. The results suggest that some people are genetically programmed to age at a faster rate, according to study co-leader Tim Spector, from King's College London.

The odds of carrying the variant are relatively high, Samani says. "In the populations we studied, about 7 percent of people carried two copies of the variant and about 38 percent of people [carried] one copy." But it's unknown whether shorter telomeres make their carriers physically appear older than they really are. "We haven't looked at that—it's an interesting question," he says; pondering how to measure the age someone looks in a follow-up study. Maybe we'll take pictures of the participants and a have a panel guess their age," he adds jokingly.

Samani, a cardiologist and professor of cardiology, is more interested in whether people carrying the variant are at a higher risk for developing age-associated illnesses like heart disease. "I see people in their eighties who have very normal arteries, and people in their forties with cardiovascular disease," he says. Previous work published by Samani has linked telomere shortening with heart disease, suggesting that biological age may be more relevant to age-related diseases than chronological age. "We've got a marker for biological aging—telomere length—so we're studying whether we can relate it to the increased risk of getting some of these age-associated diseases. That would certainly put the concept of biological aging on firm foot[ing]."

Samani now plans to investigate how the variant is making telomeres shorter. "It could be regulating TERC, but that's got to be shown in further studies," he says. People carrying the variant might further accelerate the biological aging process if they smoke, are obese or don't exercise—all of which are bad news for telomeres.

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