Life Span: You're In Control

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 and whether a person will get some diseases - 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 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," 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," Vaupel said. "That's what the evidence shows. Even twins, identical twins, die at different times," on average 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. The factors include genetic predispositions, disease, nutrition, a mother's health, subtle injuries and accidents and simply chance events, like a randomly occurring mutation in a gene of a cell that ultimately leads to cancer.

The result is that old people can appear to be struck down for many reasons, or for what looks like almost no reason at all, just chance. Some may be more vulnerable than others, and over all, it is clear that the most fragile are likely to die first. But there are still those among the fragile who somehow live on and on. And there are seemingly healthy people who die suddenly.

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 from 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."

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.

They turned to studies of families and of parents and children, but data analysis has been difficult and definitive answers elusive. 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?" 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. To do this, Christensen and his colleagues took advantage of detailed registries that included all the twins in Denmark, Finland and Switzerland born from 1870 to 1910. The twins were followed until 2004 to 2005, when nearly all had died.

Now, Christensen and his colleagues have analyzed the data. They restricted themselves to twins of the same sex, which obviated the problem that women tend to live longer than men. That left them with 20,502 members of same- sex pairs of twins, identical or fraternal. And that was enough for meaningful analyses even at the highest ages. "We were able to disentangle the genetic component," Christensen said.

But the genetic influence was much smaller than most people, even most scientists, had assumed. In a recent paper published in Human Genetics, the researchers reported their findings. Identical twins were slightly closer in age when they died than were fraternal twins.

But, 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 Christensen, was that the strongest genetic effect was for 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 80s, the 90s or even 100. The average age of death is 68.5 for men in the United States, and 76.1 for women, according to Arialdi Minio of the National Center for Health Statistics.

But 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.

A woman whose sister lived to be 100 has a 4 percent chance of living that long, Christensen says. That is better than the 1 percent chance for women in general, but still not very great because the absolute numbers, 1 out of 100 or 4 out of 100, are still so small. For men, the odds are much lower. A man whose sister lived to be 100 has just a 0.4 percent chance of living that long. In comparison, men in general have a 0.1 percent chance of reaching 100.

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, Finch says.

"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," 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, Finch pointed out. And random differences in development early in life can set the stage for deterioration decades later.

Even diseases like many cancers, which are commonly thought to be strongly inherited, are not, researchers found. In a paper in the New England Journal of Medicine in 2000, Dr. Paul Lichtenstein of the Karolinska Institute in Stockholm and his colleagues analyzed cancer rates in 44,788 pairs of Nordic twins. 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 also get it was generally less than 15 percent, about five times the risk for the average person but still not a very big risk over all.

Looked at one way, the data say that genes can determine cancer risk. But viewed another way, the data say that the risk for an identical twin of a cancer patient is not even close to 100 percent, which is what it would be if genes completely determined who would get the disease.

Dr. Robert Hoover of the National Cancer Institute wrote in an editorial: "There is a low absolute probability that a cancer will develop in a person whose identical twin - a person with an identical genome and many similar exposures - has the same type of cancer. This should also be instructive to some scientists and others interested in individual risk assessment who believe that, with enough information, it will be possible to predict accurately who will contract a disease and who will not."
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