Scientists Move Closer to Understanding Why We Age
By Eben Harrell / London, courtesy of TIME
Time waits for no man, the old truism goes, but in recent years scientists have shown that it does seem to move more slowly for some. Molecular biologists have observed that people’s cells often age at different rates, leading them to make a distinction between "chronological" and "biological age."
But the reason for the difference remains only vaguely understood. Environmental factors such as smoking, stress and regular exercise all seem to influence the rate at which our cells age. Now, for the first time, researchers have found a genetic link to cellular aging — a finding that suggests new treatments for a variety of age-related diseases and cancers.
The field of "biological aging" has in recent years focused on the long molecules of DNA contained in human cells called chromosomes. All chromosomes have protective caps at either end called telomeres. Each time a cell replicates itself (as it does before it dies), the telomeres shorten, like plastic tips fraying on the end of shoelace. Shortened telomeres have been linked to a host of age-related illnesses such as heart disease and certain cancers. (Scientists have yet to study whether telomeres influence a person’s appearance). Last year’s Nobel prize in medicine was awarded to three American scientists for their work in the field, and many scientists now believe telomeres are the closest we may come to identifying a biological clock — and our best bet for one day learning how to stop or turn back that clock.
To better understand the aging discrepancy, a team of researchers in Britain and The Netherlands scanned more than 500,000 genetic variations across the human genome. Using a population of nearly 12,000, they then attempted to pinpoint a genetic link to telomere length. (See how to prevent illness at any age.)
In a significant breakthrough, the team successfully identified that a particular gene sequence was associated with differences in telomere length between individuals. What’s more, the sequence was clustered near a gene called TERC, which is already known to play a role in the production of an enzyme called telomerase. Telomerase repairs telomeres when they shorten. "That was very exciting for us," says Professor Nilesh Samani, a cardiologist at the University of Leicester who co-led the research, published last week in Nature Genetics. "It gave us great confidence that we identified genetic variants on a pathway we already know is associated with telomere length."
The team found that around 38% of study participants carried one copy of the gene variant and that these people had telomeres that were similar to subjects three to four years older who did not carry the sequence; 7% had two copies of the DNA sequence and were on average six to seven "biologically" older.
The TERC gene is likely only one of several genes that influence telomere length, says Tim Spector of Kings College London, who co-led the study. "Our next step will be to use whole genome sequencing to expand our search from 500,000 to 50 million [genetic] markers. TERC is almost certainly only the first piece of the genetic puzzle," he says.
Spector and Samani say that understanding the components that determine telomere length may one day help researchers devise new treatments for age-related diseases, particularly heart disease (the study was partially funded by the British Heart Foundation). "I see in my practice 80-year-olds with healthy coronary arteries and 40-year-olds with heart disease. We may be on our way to explaining the genetic component in the explanation for why this is so, and so expanding our knowledge of the disease and how to treat it," he says.
But Samani also says that telomere research offered no quick fixes, and telomere-based treatments were still a long way off. The reason for this is that the telomeres — while potentially lowering the risk of heart disease — also plays a role in the development of cancer cells. "We all probably develop cancer cells that don’t get past a few replications because of the effect of normal telomere shortening. If you make cells immortal by allowing them to replenish their telomeres, you may raise the risk of many nasty cancers considerably."
The bottom line, Samani says, is that scientists remain a long way from developing an elixir of youth, however alluring that goal may be. Reporting on his research, Britain’s Daily Mail announced that Samani had found "the Peter Pan gene" — a headline Samani greeted with a weary smile. "Aging and death will remain central to our biology, at least for as long as I can foresee," he says.
