• home

The Problem With Older Men’s Sperm

September 9, 2012

By Amy Alkon

The Problem With Older Men's Sperm
Judith Shulevitz writes in The New York Times:

A woman is born with all the eggs she'll ever carry. By the time a man turns 40, on the other hand, his gonad cells will have divided 610 times to make spermatozoa. By the time he's in his 50s, that number goes up to 840. Each time those cells copy themselves, mistakes may appear in the DNA chain. Some researchers now think that a percentage of those mistakes reflects not just random mutations but experience-based epigenetic markings that insinuate themselves from sperm to fetus and influence brain development. Another theory holds that aging gonad cells are more error-prone because the parts of the DNA that should have spotted and repaired any mistakes have been epigenetically tamped down. In any case, we now know that the children of older fathers show more signs of schizophrenia, autism and bipolar disorder than children of younger ones.In a meta-analysis of a population study of more than a million people published last year, Christina Hultman of the Karolinska Institute of Sweden concluded that children of men older than 50 were 2.2 times as likely to have autism as children of 29-year-olds, even after the study had factored out mothers' ages and known risk factors for autism. By the time the men passed 55, the risk doubled to 4.4 times that of 29-year-olds. Can the aging of the parent population explain the apparent spike in autism cases? A study published last month in Nature that used whole-genome sequencing on 78 Icelandic families made the strongest case to date that as fathers age, mutations in their sperm spike dramatically. Some of the mutations found by the researchers in Reykjavik have been linked to autism and schizophrenia in children.
In his Washington Heights laboratory at the New York State Psychiatric Institute, Jay Gingrich, a professor of psychobiology, compares the pups of young male mice (3 months old or so) to those of old male mice (12 to 14 months old). The differences between the pups, he told me, weren't "earth-shattering" -- they weighed about the same and there weren't big gaps in their early development. But discrepancies appeared when the mice grew up. The adult offspring of the older fathers had less adventuresome personalities; they also reacted to loud noises in unusual ways that paralleled reactions evinced by schizophrenics who heard similar sounds.
Still, Dr. Gingrich said, "the differences were subtle" until he decided to pool the data on their behavior and graph it on a bell curve. A "vast majority" of the children of the older mice were "completely normal," he said, which meant their score fell under the upside-down parabola of the curve. The real differences came at the tails or skinny ends of the bell curve. There was about a sixfold increase in likelihood that one of the "abnormal outliers," mice with cognitive or behavioral handicaps, "would come from an older father." Conversely, the super-high-performing mice were about six times more likely to come from a younger father. "I'm an inherently skeptical person," Dr. Gingrich told me, but he was impressed by these results.