Down Syndrome one of the many disorders due to older paternal age and in this case older maternal age

June 26, 2008

Fact or Fiction: Men Have a Biological Clock
Does male fertility have an expiration date?
By Anne Casselman


TICKING CLOCK: Male fertility declines just like female fertility.

The female biological clock—its tick-tock marking the decline of fertility that grows louder as a woman reaches middle age—is deeply ingrained in popular consciousness. Take this scene from the film Bridget Jones's Diary: Bridget's Uncle Geoffrey reminds her that as a career girl she "can't put it off forever," alluding to her declining fertility. His wife Una chimes in: "tick-tock, tick-tock," her finger wagging like a metronome.

The biological clock, although just a metaphor, refers to a real phenomenon: Women over 35 years of age are only half as likely to become pregnant in the most fertile part of their menstrual cycle than women younger than 26.

So do men suffer from the same thing?

"For women, a biological clock is a decline in fertility and an increased chance of having genetically abnormal babies as they age," says Harry Fisch, director of New York City's Male Reproductive Center and author of The Male Biological Clock: The Startling News About Aging, Sexuality, and Fertility in Men. "And that's exactly what's happening with men."

So how did Indian farmer Nanu Ram Jogi sire a healthy child at the age of 90 last year? Such a feat would be impossible for a woman, even in an age when Carmela Bousada, 67, gave birth to twins in January 2007 after lying about her age to the doctors who gave her in vitro fertilization. Whereas fertility declines along with testosterone levels as men age, it doesn't drop to zero.

Still, Jogi is definitely the exception rather than the rule. One study found that the odds of fatherhood for those under the age of 30 was 32.1 percent compared with 20 percent over the age of 50, signifying a 38 percent drop in male fertility across that age gap.

One study examined 97 men between the ages of 22 and 80 and found that as they aged their semen volume decreased by 0.001 ounce (0.03 milliliter) per year from an average total of 0.09 ounce (2.7 milliliters) and their "total progressively motile sperm count"—a rough index for the fertility potential of one's sperm based on its movement—decreased about five percent with each year they aged.

Fisch and his colleagues have also found that the children of women over 35 whose babies' fathers were also of that age were more likely to have Down's syndrome than offspring whose fathers were younger.

In other studies, older men were more likely to father children with mental illness or other deficits. Roughly 11 children out of a thousand conceived by men over age 50 developed schizophrenia compared with under three children out of a thousand for fathers under 20 in one study from the Archives of General Psychiatry. And the children of men 40 years or older were nearly six times more likely to have autism spectrum disorders than kids begot by men under 30.

So do men's sperm get staler over time? To maintain sperm levels, cells known as germ cells must continue dividing. After all, men find ways to dispose of sperm—ahem—and once ejaculated they only survive for several days. By the age of 50, these germ cells will have divided 840 times. Each one of those divisions is an opportunity for something to go wrong. "There's more of a chance to have genetic abnormalities the more the cells divide," Fisch says. In sperm these mutations dot the genes with changes in the basic structure of the DNA—and can lead to problems in the resulting offspring.


Bioengineer Narendra Singh of the University of Washington in Seattle and his colleagues compared the sperm of men of different ages. Sure enough, sperm in men older than 35 had more DNA damage than that from younger men. And although unhealthy sperm are supposed to commit cell suicide, some of the sperm they looked at had lost that ability to "take one for the team"—meaning they'd be around to fertilize an egg. "This may lead to offspring with defective DNA, which may translate to mental and physical defects," Singh says.

Can men prevent this damage? No, but they may be able to mitigate it. There are factors within men's control that can accelerate adverse effects: alcohol, smoking, drugs and environmental pollution—even coffee consumption. So avoid them, says Singh.

Still, even after correcting for various lifestyle factors, the DNA of sperm are increasingly damaged with advancing age.

"The question is, can we reverse the [male] biological clock?" asks Fisch, who is studying various ways to keep sperm healthy.

Perhaps Bridget Jones's Uncle Geoffrey and Aunt Una should have chastised her love interest, Mark Darcy, too, for procrastinating procreation. That "tick-tock, tick-tock," it would seem, applies to both sexes.