"In our first study, looking at every pregnancy in Jerusalem from 1964 to 1976, we found that increased age in the father predicted increased cases of schizophrenia in the children," explains Malaspina, who was on the team doing the work. "In our second study we found that when the cases arose from new mutations—not familial inheritance—it almost always could be traced to the genetics of the father. Somewhere between a quarter and a third of the cases could be explained only by the age of the father—a threefold risk linked to fathers older than 50 compared with those in their 20s." Studies in Sweden and California produced almost identical results.
The autism findings are even more disturbing: Men 40 and older in the Israeli study were almost six times as likely to have offspring with autism than men under 30. Some researchers believe that older fathers may hold a clue to the vast upsurge in autism cases in the past decade. "With older and older couples having children—in the past two years, for the first time, more babies are being born to women over age 30 than under age 30, and on average, male partners tend to be older than female partners—it's very feasible that paternal age is a major predictor of autism," asserts Fisch.
Minor Damage is the Worst Kind
Perhaps the creepiest aspect of these findings is that a little genetic damage in men's sperm may actually be worse than a lot of damage. "When we started doing the research, our first concern was fertility, and these studies do show that fertility maybe compromised by DNA damage. But that's not the most important thing," declares Charles Muller, lab director of the Male Fertility Clinic at the University of Washington in Seattle.
The greater threat to offspring is the less flagrant DNA damage that gets passed on. Experts like Muller believe that a substantial amount of the damage is caused by free radicals—the destructive, highly reactive particles produced by our body's energy factories, the mitochondria, as we metabolize oxygen. "One of the scariest things we're finding is that sperm DNA is damaged by even low levels of free radicals. Whereas high levels of damage lead to infertility, miscarriages, or spontaneous abortions, low levels chew up the DNA but the sperm can still fertilize," Muller states.
Complicating matters, sperm is incapable of repairing itself; Muller and his colleague Narendra P. Singh find that as men age, natural processes such as apoptosis—in which damaged cells naturally commit suicide to protect the body—become increasingly less efficient and less able to eliminate damaged DNA. Resulting defects may not show up until offspring are adults and it's too late to trace the cause. Damage may then be passed from one generation to the next.
"In short, the biggest genetic threat to society may not be infertility but fertile old men," says University of Wisconsin in Madison geneticist James F. Crow.
The Playing Field Levels
These findings have profound implications for any potential parent. Women may increasingly feel they share the onus of potential infertility and birth defects with men. Older women, focused though they are on their own reproductive timetable, may increasingly view their partner's age with a wary eye. When both parents are aging, the risks to offspring multiply. "If women are under age 35, the father's age may not matter that much, but if the mother is over 35, advanced male age can be a real problem." says Jabs.
For men, the findings may be, above all, a clarion call to take better care of themselves. "This should make men reconsider their role and responsibility in childbearing," says Barbara Willet, of the Best Start childhood resource center in Ontario, Canada. "Aging in men is an important issue, but health is the key issue. It's as if we're suddenly aware that men who want to be fathers need to be healthy, too."
One key is testosterone, necessary for the maturation of sperm. "If you have less testosterone, you have worse sperm." Testosterone naturally starts to decline in the 30s, but also varies based on factors from weight to heart health. "Fat cells in a pot belly overheat the testes and break testosterone down; clogged arteries break it down. Whatever hurts your heart, hurts your penis," Fisch states.
Men typically don't think about their health, and we need to get them to. If you're drinking or smoking, if you're working in toxic environments with pesticides, X-rays, solvents, or ionizing radiation, these things affect you as well as women, and will ultimately affect the children you conceive.
Alarming though the findings may be to some, researchers have a clear directive: "Don't panic." "The research is still fresh," says Crow, "and more needs to be done before we start making sweeping recommendations like urging people to have children younger, or telling men to freeze their sperm after their 20s. I don't advocate asking the general public to change at this point, because while some of these mutations cause very severe effects, in the totality of things that can go wrong, this is not that large a part of the picture."
Freezing sperm may sometimes be the way to go. While frozen sperm may not be quite as potent as when it is fresh, it is not a proven problem. Since the turn of the last century, sperm of domestic animals has been frozen safely for as long as 75 years, says Muller. And frozen sperm is used routinely in humans for artificial insemination. Pregnancy rates and childbirth are right up there with regularly conceived birth, and there is no substantial DNA breakdown. If you're going to get a vasectomy, join the Army, or go through cancer therapy, "I'd advise you to freeze your sperm beforehand," Muller says.
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