The Weak Link Between Genes and Longevity

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This surprised me. The correlation between genetics and longevity may be a lot weaker than you think, with "only 3 percent of how long you live compared to the average person ... explained by how long your parents lived":

Live Long? Die Young? Answer Isn’t Just in Genes, by Gina Kolata, NY Times: Josephine Tesauro never thought she would live so long. At 92, she is straight backed, firm jawed and vibrantly healthy... Mrs. Tesauro does, however, have a living sister, an identical twin. But she and her twin are not so identical anymore. Her sister is incontinent, she has had a hip replacement, and she has a degenerative disorder that destroyed most of her vision. She also has dementia. “She just does not comprehend,” Mrs. Tesauro says. Even researchers who study aging are fascinated by such stories. How could it be that two people with the same genes, growing up in the same family, living all their lives in the same place, could age so differently?

The scientific view of what determines a life span or how a person ages has swung back and forth. First, a couple of decades ago, the emphasis was on environment, eating right, exercising, getting good medical care. Then the view switched to genes, the idea that you either inherit the right combination of genes that will let you eat fatty steaks and smoke cigars and live to be 100 or you do not. And the notion has stuck, so that these days, many people point to an ancestor or two who lived a long life and assume they have a genetic gift for longevity.

But recent studies find that genes may not be so important in determining how long someone will live... — except, perhaps, in some exceptionally long-lived families. That means it is generally impossible to predict how long a person will live based on how long the person’s relatives lived.

Life spans, says James W. Vaupel, who directs the Laboratory of Survival and Longevity at the Max Planck Institute for Demographic Research in Rostock, Germany, are nothing like a trait like height, which is strongly inherited. “How tall your parents are compared to the average height explains 80 to 90 percent of how tall you are compared to the average person,” Dr. Vaupel said. But “only 3 percent of how long you live compared to the average person can be explained by how long your parents lived.”

“You really learn very little about your own life span from your parents’ life spans,” Dr. Vaupel said. “...Even twins, identical twins, die at different times.” On average, he said, more than 10 years apart. The likely reason is that life span is determined by such a complex mix of events that there is no accurate predicting for individuals. ...

Some diseases, like early onset Alzheimer’s and early onset heart disease, are more linked to family histories than others, like most cancers and Parkinson’s disease. But predisposition is not a guarantee that an individual will develop the disease. Most, in fact, do not get the disease they are predisposed to. And even getting the disease does not mean a person will die of it.

There are, of course, some valid generalizations. On average, for example, obese men who smoke will die sooner than women who are thin and active and never get near a cigarette. But for individuals, there is no telling who will get what when or who will succumb quickly and who will linger. “We are pretty good at predicting on a group level,” said Dr. Kaare Christensen, a professor of epidemiology at the University of Southern Denmark. “But we are really bad on the individual level.”

Looking to Twins

...It seems like common sense. Family members tend to look alike. And many characteristics are strongly inherited — height, weight, a tendency to develop early onset heart disease or to get diabetes. Even personalities run in families. Life span would seem to fit with the rest.

But scientists have been trying for decades to find out if there really is a strong genetic link to life spans and, if so, to what extent. ... If a family’s members tend to live to ripe old ages, is that because they share some genes or because they share an environment? “Is it good socioeconomic status, good health or good genes?” Dr. Christensen asked. “How can you disentangle it?”

His solution, a classic one in science, was to study twins. The idea was to compare identical twins, who share all their genes, with fraternal twins, who share some of them. ... Dr. Christensen and his colleagues have analyzed the data ..., 10,251 pairs of same-sex twins, identical or fraternal. And that was enough for meaningful analyses even at the highest ages. “We were able to disentangle the genetic component,” Dr. Christensen said.

But the genetic influence was much smaller than most people, even most scientists, had assumed. ... Identical twins were slightly closer in age when they died than were fraternal twins. But, Dr. Christensen said, even with identical twins, “the vast majority die years apart.”

The investigators also asked when the genetic factor kicked in. One hypothesis, favored by Dr. Christensen, was that the strongest genetic effect was on deaths early in life. He thought that deaths at young ages would reflect things like inherited predispositions to premature heart disease or to fatal cancers.

But there was almost no genetic influence on age of death before 60, suggesting that early death has a large random component — an auto accident, a fall. In fact, the studies of twins found almost no genetic influence on age of death even at older ages, except among people who live to be very old, the late 80’s, the 90’s or even 100. ...

Finding Randomness

Even though there may be a tendency in some rare families to live extraordinarily long, the genetic influence that emerged from the studies of twins was significantly less than much of the public and many scientists think it is. ...

Those data fit well with animal studies, says Caleb Finch, a researcher on aging at the University of Southern California. Genetically identical animals — from worms to flies to mice — living in the same environments die at different times.

The reason is not known, Dr. Finch said. “It’s random,” he said. “Since we can’t find any regular pattern, that’s the hand wave explanation — randomness.” And random can mean more than one thing.

“There are two phases of randomness,” Dr. Finch said. “There’s the randomness of life experiences. The unlucky ones, who get an infection, get hit on the head or get mutations that turn a cell into cancer. And there are random events in development.”

Random cell growth and division and random differences in which genes get turned on and how active they are during development can cause identical twins to have different numbers of cells in their kidneys and even different patterns of folds in their brains, Dr. Finch pointed out. And random differences in development early in life can set the stage for deterioration decades later. ...

[E]ven diseases commonly thought to be strongly inherited, like many cancers, are not, researchers found. ... They found that only a few cancers — breast, prostate and colorectal — had a noticeable genetic component. And it was not much. If one identical twin got one of those cancers, the chance that the other twin would get it was generally less than 15 percent, about five times the risk for the average person but not a very big risk over all. ...

[T]he general picture is consistent in study after study. A strong family history of even a genetically linked disease does not guarantee a person will get it, and having no family history does not mean a person is protected. Instead, chronic diseases strike almost at random among the elderly...

Matt McGue, a psychology professor at the University of Minnesota who studies twins, contrasts life spans with personality, which, he says, is about 50 percent heritable, or attention-deficit hyperactivity disorder, which is 70 to 80 percent heritable, or body weight, which is 70 percent heritable.

“I’ve been in this business for a long while, and life span is probably one of the most weakly heritable traits I’ve ever studied,” Dr. McGue said. ...