Check Out this Excellent Newsweek Article On the Genetic Male Biological Clock

For Whom The Clock Ticks
A growing body of research supports the idea that there are biological disadvantages to late-in-life fatherhood. But will society's view of male fertility ever change?

By Daniel Heimpel | Newsweek Web Exclusive
Apr 22, 2009
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In season two of Bravo's wildly popular television series "Millionaire Matchmaker," host Patti Stanger rants against older men who perpetually search for 20-somethings to date. What Stanger knows intuitively and what researchers are illustrating empirically, is that men 50 and older, no matter their financial stability, aren't always the greatest catch.

Even if they can theoretically father children till the day they die, a growing compendium of knowledge points to a male "biological clock" largely driven by the replication of sperm with damaged DNA. According to a number of recent studies, offspring of older men have increased chances of a wide range of problems from autism to psychiatric disorders such as schizophrenia. Unlike women, who are equipped with their life's supply of eggs at birth, men replicate sperm from their bar mitzvah to their funeral. It's like a Xerox copy of a Xerox copy millions of times over. The damage can be caused by glitches in the process of replicating DNA millions of times over, reduced efficiency of the DNA repair mechanism, or attributed to environmental factors like stress, smoking or heavy drinking.

But the bottom line is: as men age, the percentage of damaged sperm they carry in their testes tends to increase. "Men are making millions of sperm all the time, and the chance for a copy error is much higher," says Dr. Ethylin Jabs, director of the Center for Craniofacial Development and Disorders at Johns Hopkins, who has conducted extensive research on paternal age and mutations within sperm. Where older women may be concerned about the viability of their remaining eggs, the problem for men, says Jabs, is "quantity not quality."

Semen samples of men over 45 showed impairment to sperm in three categories: their motility (swimming capability), vitality and DNA integrity, according to Dr. Sergey Moskovtsev of Mount Sinai Hospital's Department of Pathology and Laboratory Medicine in New York. Moskovtsev's research shows that men older than 45 have twice as much damage to their sperm as men under 30. Researchers believe that an increase in the percentage of damaged sperm can have a number of consequences.

A report released in PLoS Medicine last month establishes a link between reduced intelligence and children who were fathered by older men. Using a sample of 33,000 children tested at the ages of 8 months, 4 years and 7 years, John McGrath of Australia's Queensland Centre for Mental Health Research and colleagues found that children of older fathers ranked consistently lower in cognitive ability tests than the offspring of younger fathers. For example, 7-year-old children born to 50-year-old dads performed two IQ points lower than peers born to 20-year-old fathers. This difference in IQ is of course subtle, and McGrath says that the results of his study shouldn't be cause for individual men to stop having children.

But he cautions that the mounting studies pointing to a male biological clock are worth considering on a macro level. "As a researcher, I am concerned that we have neglected the issue of paternal age," McGrath says. "Worryingly, the mutations associated with advanced paternal age can be passed on to the next generation. As the population delays parenthood, these mutations could, theoretically, accumulate. Other researchers—not me—have called this process a 'mutational time-bomb'."

Normally, individual sperm with impaired DNA would perform a kind of cell hara-kiri, killing themselves in a process called apoptosis. But research out of the University of Washington has shown that the sperm of men over 35 are less likely to go through that process. Coupled with higher amounts of semen bearing damaged DNA, the likelihood of a child born with an abnormality increases. In a study of hundreds of thousands of psychiatric records conducted by the Israeli draft board in the 1980s, Dr. Abraham Reichenberg of the Mount Sinai School of Medicine, New York, and the Institute of Psychiatry, King's College London, and colleagues showed a six-time increase in autism spectrum disorders for children of fathers over 40, compared with those 29 years and younger.

Since that report came out in 2006, Reichenberg says that efforts to link autism and other psychological disorders to older dads have been bolstered by similar results among sample groups from different countries. Another psychological disorder that has been linked to damaged sperm is schizophrenia. Men over 50 are 3 times as likely to have offspring with the debilitating mental disorder than fathers under the age of 25....