Living Longer: Reaching 114 Is Not Just Good Genes

Jan. 4, 2012 — -- A man and a woman whose lives literally reached all the way back to the horse and buggy days are teaching modern scientists a few things about getting old. Both lived more than 114 years -- their names and exact ages are being withheld to protect their privacy -- and both had about the same number of bad genes as the rest of us.

Those genes, called variants, should have destroyed their health and even killed them long before they reached that age. Alzheimer's, cancer, heart disease, the whole bit.

But they didn't, and therein lies a scientific drama. The man fought off cancer in his mid-70s and for the rest of his life relied on a single daily medication, aspirin. He was in excellent health, both mentally and physically, until just before he died. The woman was nearly as fortunate, although she grew frail after turning 108, and her mind slipped a little toward the end.

How did they do that?

Both had a few gene variants -- variations in some genes that make us different from one another -- that predisposed them to deadly diseases. All of us have some, so in that sense we are quite like folks who live well past 100.

"Those genes also predisposed them to death, so how did they get to 114?" said Thomas Perls, founder and director of the New England Centenarian Study at Boston University.

Perls and his colleagues found the answer to that question by completing the genome sequences for both the man and the woman in what is believed to be the first such study. Scientists from Boston University, the University of Florida at Gainesville, and the Scripps Research Institute participated in the research.

The study, published this week in Frontiers in Genetics, found that the participants had other gene variants that somehow disabled the genes that would have otherwise killed them both.

In other words, they had good genes that fought off the bad genes, automatically achieving what some of the best minds in science have tried to do -- with very little success -- through genetic engineering.

'Supercentenarians'

The participants in the study, who were not related, are called "supercentenarians," meaning they did what very few of us will do, living past the age of 110. Only about one out of every five million persons in developed countries live that long.

And they did it against seemingly impossible odds. All of us have gene variants, or genes that have mutated into genes that are somewhat different and possibly dangerous. Some experts had long thought that supercentenarians somehow escaped that, but the new study proves that's false. Both the man and the woman had many mutated genes that left them predisposed to disease comparable to levels in the population as a whole.

"The woman carried at least 30 mutations linked to Alzheimer's disease, 201 mutations associated with cancer," and "52 mutations associated with heart disease, 136 mutations associated with diabetes, 12 linked to macular degeneration that she was diagnosed with after the age of 100 years," to cite just some of the variants listed in the study.

"The man carried 37 mutations associated with increased risk for colon cancer," the study continues, noting that it was advanced enough that it should have metastasized and killed him, but "amazingly," it didn't. "His load of disease-predisposing variants was comparable to the female subject," the study added, so on the surface, neither seemed to have a prayer of making it past their nineties.

"What allows them to get to these extreme old ages is probably some protective genes that not only slow down aging, but also protect them from the bad variations," Perls said in a telephone interview. "It's almost like they are trumping the bad variants."

Perls said both participants had some genes that are widely regarded as associated with greater life spans, "but there are others that they didn't have." So it wasn't just a matter of having the right longevity genes.

"That points to just how incredibly complex this puzzle is," he said. "It involves probably hundreds of variations of hundreds of different genes, both good and bad."

Much to their dismay, scientists have found that it isn't as simple as turning a gene on or off to defeat a disease, because many genes do many things, and like all medical treatments, there can always be a downside.

It's risky to draw many conclusions from this particular study, because as Perls himself noted, two persons are not nearly enough. So many scientists at other institutions are launching broader studies in hopes unraveling this "complex puzzle" further.

What is clear at this point is that the lives of most supercentenarians are surprisingly similar. They tend to enjoy good health until very late in life, according to Perls who has been studying this for more than a decade, and their siblings also tend to lead long, healthy lives.

Many of them have serious diseases, including cancer, in their 80s or 90s, "but they handle them so much better than the general population," Perls said, possibly because good variants are controlling the bad variants, as suggested in this study.

As a result, he said, "they don't experience any disability, on average, until around the age of 93. So it's really only the last three or four years of their lives that they have any kind of age-linked disease."

Perls, who has spent a lot of time with supercentenarians, calls them "living historical treasures." Both participants, even near the end of their lives, could vividly recall the days when horse-drawn buggies fought gas-belching monsters for the right-of-way.

People in cars were always getting flat tires, the woman told him once. She said they didn't have enough sense to get a horse.