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Can we live longer?

As more people hit the century mark and beyond, scientists search for the key. Genes, diet and inflammation are just some of the clues.

December 25, 2006|Andreas von Bubnoff and Christie Aschwanden | Special to The Times

CENTENARIANS were a rare breed when Jeanne Louise Calment was born in 1875. But by the time she died in 1997 at the record-setting age of 122 years and 164 days, her club was distinctively less elite.

Today, centenarians comprise the fastest-growing segment of the population. In developed countries, their numbers have been doubling every five to seven years, and the age that they achieve has been rising steadily -- from 110 in 1930 to 120 in 1995.

Trailing along in their impressive wake, the less-remarkable folks are doing better too. The average U.S. life expectancy has been increasing for more than 100 years and hit a record high in 2004: 80.4 years for women and 75.2 years for men.

Just how long can this go on?

It is a matter of fierce debate. Scientists aren't sure if we will ever be able to expand human life span to 100 years or beyond for most people, not just the lucky few favored by genes and environment. They're also divided on whether science will come up with a pill or other remedy that lets people break through what seems like a biological barrier unbreachable by even the Calments of this world.

The answers are intertwined with one of the most basic biological mysteries: why creatures, be they humans, rats or rhinos, all wither and die. That riddle is yet to be solved -- but scientists are gathering tantalizing clues.

Just last month, a study reported that mice manipulated to have a slightly lower body temperature live longer than mice with a regular body temperature. Another reported that a substance found in red wine -- resveratrol -- extended the life span of overfed, obese mice.

A slew of theories on aging have been suggested over the centuries. Some people, turning to the Bible, believed it was moral transgression. Others -- from ancient Greece to the 19th century -- held that aging came from a progressive loss of heat, moisture or both.

Today, scientists are focusing on a few leading contenders -- such as damage to cells and tissues from highly active chemicals called free radicals, chronic inflammation, a built-in limit to the number of times our cells can divide, or a slow, steady stiffening of tissues by a lifetime of exposure to sugar.

All of these are only theories at this point -- albeit with some science to support each of them, says Dr. Robert Butler, president and chief executive of the International Longevity Center, a not-for-profit think tank in New York City. None has reached the point where it can fully explain aging.

Tantalizingly, scientists have discovered that they can extend life span in animals by restricting how much they eat: In rats and mice, a 30% reduction in caloric intake extends life span by a third.

And they've found that tinkering with certain genes allows rodents and other animals to also live longer.

The clues inside

One gene they're interested in is known as Sir2: Increasing the number or activity of Sir2 genes in fruit flies and worms can extend their life span by 30% to 50%, says MIT researcher Leonard P. Guarente. He says he's now testing whether the same is true in mice.

The Sir2 gene appears to play a key role in extending life span when animals restrict their calories, at least in worms, yeast and flies. Thus, understanding the human version of the gene should offer clues as to why we wither and die.

As it turns out, that gene directs formation of a key enzyme that senses how much immediate energy body cells have to sustain themselves with -- and if those levels are low, it activates emergency stress responses.

Researchers are now looking for drugs that can increase the activity of that enzyme. If they're able to do so, and if the drugs act as they hope they will, "I believe we will break [the 122-year age] limit," says David Sinclair, an associate professor of pathology at Harvard Medical School.

They have made some headway. Three years ago, Sinclair's lab discovered that resveratrol, a compound found in red wine and grape skins, seems to activate that enzyme. A study in February showed that feeding resveratrol to fish extends their maximum life span by 59%.

Another study, published in the journal Nature in November, showed that obese mice -- which normally have shortened life spans -- can live just as long as lean mice if they're fed resveratrol. The mice had healthier livers and heart tissue, more normal blood sugar levels and the agility of lean mice.

This doesn't mean resveratrol's an anti-aging elixir. It's unclear if the chemical would have the same effects in humans. And even if it did, people would have to ingest it in huge doses -- on the order of dozens of supplement pills or hundreds of bottles of red wine a day, says Joseph Baur of Harvard Medical School, lead author of the obese-mouse study.

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