longevity

Fountain of Youth Bubbles in Brains of the Oldest Old
By Cassie Ferguson

Death and taxes are still certain, but according to a Medical School study, the mental infirmities of old age are not.

Neuropsychological examinations and autopsies of people who live past 100 show that they can live to the end with sound minds, report the researchers in the upcoming issue of International Psychogeriatrics.

"It has been common thinking that dementia's inevitable with old age. That isn't so. We're studying centenarians whose thinking is perfectly clear. And their brain autopsies confirm what we see," said Margery Silver, associate director of the New England Centenarian Study and clinical instructor in psychology at the Medical School.

"I marvel at these brains. Some could pass for individuals 20 or 30 years younger," said Kathy Newell, a clinical fellow in neuropathology at Massachusetts General Hospital. "Many were basically healthy looking brains with a nice size, normal weight, and little or no evidence of atrophy."

Silver and her colleagues at the Centenarian Study tested the cognitive function of 69 centenarians, finding that although the hyper-aged frequently have some degree of dementia, 20 percent have survived the years in perfect mental health.

Guessing that the brains of centenarians might mirror the results of the neuropsychological tests, they asked pathologists from Massachusetts General Hospital to take a post-mortem look at the condition of study subjects who had willed their brains to science.

The autopsies revealed that half had resisted the onslaught of tiny strokes as well as fatty plaques and proteins thought to choke blood vessels and strangle brain cells as brains age, possibly causing Alzheimer's disease and dementia. Of the six examinations reported in the paper, none was diagnosed with Alzheimer's disease.

Since the brains of the centenarians can be unexpectedly free from the physical proof of old age, Silver suggested that dementia sometimes attributed to people who have reached at least 100 might be misattributed and even reversible.

"There are lots of treatable causes for dementia. Doctors may be missing something that's curable. The dementia might be caused by something like depression, medication for heart disease, or B-12 deficiency," she said.

This is good news for the projected 500,000 to 4 million people, who'll be blowing out at least 100 birthday candles in the middle of the next century.

The Old Genes vs. Environment

How people preserve both mental and physical health past their 70s and 80s -- which weeds out the majority of the population -- has been pinned alternately on genetics and the environment. As it turns out, said Thomas Perls, director of the New England Centenarian Study and an instructor at the Medical School, "aging is a complex mix of genes and environment."

On the genetics side, a group in Japan recently reported in the British medical journal Lancet that more than half of the centenarians they studied carry an otherwise rare DNA sequence for three genes found in the cellular power-generating plants known as mitochondria. Although scientists still are not sure of the role those sequences play, they may provide a survival advantage. One possibility is that the unusual bit of DNA might cause the mitochondria to generate energy more efficiently, which might then lower the production of oxygen radicals thought to be tied to aging.

Centenarians may possess other preservative genes that somehow ward off detrimental environmental effects like ultraviolet radiation, said Perls. In earlier work also conducted in collaboration with researchers at Massachusetts General Hospital, nonagenarians and centenarians were found to have a much lower frequency of a gene called apolipoiprotein E4, which has been associated with an increased risk for developing Alzheimer's disease.

Seeking further evidence for a genetic explanation for longevity, Perls is currently searching through the DNA of centenarian sibling pairs for clues.

If genes aren't entirely responsible for centenarians escaping or at least markedly delaying killers like Alzheimer's, strokes, hypertension, cancer, and heart disease, they can credit their survival to lifestyle.

Most centenarians live a life of moderation -- avoiding cigarettes and excessive amounts of alcohol -- and eating well.

They stay active; walking, dancing, and, reportedly, even driving. But the real key to their longevity may be hidden inside their heads, not their bodies, said Silver, who marvels at working with people many decades older than she.

"They deal with stress well, bouncing back from tragic events that would devastate other people," she said, noting that these are people who have survived two World Wars and the deaths of many people around them.

In addition to keeping up their spirits, centenarians stay mentally healthy by exercising their minds. Ellen Bubrick, a research assistant at the Centenarian Study, said that the healthiest oldsters she's met stay active through diversions like reading, writing, and painting.

Whether sustained by their DNA, their environment, or their good luck, those headed for Methuselian maturity appear to age more slowly than most.

Last September, Perls found that centenarian women were more likely to have had children until their 40's, an age when most women are approaching menopause. The study, reported in the journal Nature, implies that people who make it to age 100 live according to an adjusted life span that's been stretched a few decades beyond average.

"Our observation is that the whole aging process is slowed down," said Silver. "These people act and look much younger than you would expect."