A Man's Shelf Life

A Man's Shelf Life

By: Mark TeichPage 2 of 4


Male versus Female Mutations

Scientists have long known that advanced paternal age (like increased maternal age) played some role in fertility problems and birth defects. Yet because the reports mainly involved children who died before birth or who had extremely rare disorders, no one really rang the alarm. Now, with studies linking the father's age to relatively frequent, serious conditions like autism, schizophrenia, and Down syndrome, the landscape is shifting.

Women have unfairly borne the brunt of the blame for birth defects. When the conditions were familial, passed on through chromosomal lineage, women were somehow widely believed culpable, even though such defects can be traced to either partner. "But what we're finding now is that in humans as well as in other mammals, when there's a new genetic change—called 'de novo or sporadic point mutation'—it almost always happens in the male parent," says Dolores Malaspina, chair of psychiatry at New York University Medical Center. And these de novo mutations increase in frequency with the age of the male parent.

These mutations could reflect the differences in male and female reproduction, notes Jabs. By the time females reach their teen years, their eggs have already been formed—just one new egg matures each month. Men, on the other hand, produce millions of sperm cells every time they ejaculate. After each ejaculation, they must literally replicate those cells, and each replication multiplies the chance for a DNA "copy error"—a genetic chink in the sperm DNA. The more ejaculations a man produces, the greater the chance for chinks to arise, leading to increased point mutation and thus increased infertility and birth defects. While a woman's reproductive capacity halts more or less abruptly after all her eggs have been used up somewhere in their forties or fifties, men experience a longer, more gradual winnowing and disintegration. "We believe that something in men's DNA replication machinery keeps becoming less efficient and less accurate with age, and the problems accumulate," says Jabs.



A Chilling Finding
The biggest news—the father's role in brain disorders—has come to light largely because of research from Israel, where birth records routinely include the age of the male parent. The first unsettling finding linked paternal age and schizophrenia.

"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.