Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35.

There is enough research to urge men and women who want children to have them in their twenties and very early 30s. It doesn't matter if there are 100 papers finding that paternal age is the major cause of spontaneous mutations because it is not an idea that is popular.

The latest finding, published last month: Older fathers are more likely to have children with autism. Researchers tracked 387,000 people born in Israel and concluded the odds of fathering an autistic child are about 6 in 1,000 for men under 20. When a man reaches 50, those odds shoot up to about 52 in 1,000.
"The optimal time for a man to father a healthy child is the same as for a woman — 25 or so," says Dolores Malaspina, a psychiatry professor at New York University and coauthor of the study.


Some of the statistics are quite alarming, however. Of the nearly 6 million fertility problems in the US each year, roughly 40% of them are attributed to the man. Of all the babies born with Down Syndrome to women over the age of 35, HALF of them are actually sperm-related. (Source for both statistics: Dr. Harry Fisch, director of the Male Reproductive Center at New York-Presbyterian Hospital/Columbia University Medical Center.) There are other studies out there that are still being discussed, with possible links between the male biological clock and diseases such as autism and schizophrenia.

Scientific Evidence Points to Male Biological Clock
Symptoms Include Declining Fertility, Lowered Testosterone Levels and Increased Risk of Heart Disease, Diabetes and Genetic Abnormalities Such as Autism

Birth Defects. As with advanced maternal age, advanced paternal age is associated with an increased incidence of birth defects due to decreased genetic quality of sperm. Men 40 and older are nearly six times more likely to have offspring with autism than men younger than 30, even after controlling for maternal age and other variables. Other defects associated with elevated paternal age include schizophrenia, Down syndrome and genetic abnormalities.


Advanced paternal age: How old is too old? Isabelle Bray, David Gunnell and George Davey Smith
Department of Social Medicine, University of Bristol, UK
Correspondence to: Dr I Bray Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK; Issy.Bray@bristol.ac.uk
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Average paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. This commentary aims to contribute to such a debate. Accumulated chromosomal aberrations and mutations occurring during the maturation of male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia. Adverse health outcomes should be weighed up against advantages for children born to older parents, mindful that these societal advantages are likely to change over time.


Birth Defects Higher Among Children with Older Fathers
Older men have an increased risk of having a child with abnormalities, new research suggests.
The common belief is that there is no age limit for men when it comes to fathering a child. Unlike women who undergo menopause, men do not have a fixed “andropause”. However, this view is being challenged as new evidence shows that the rates of birth defects such as achondroplasia (short stature) and autism is higher among children with older fathers.
A recent study carried out at a large Israeli army database found that children of men over 40 were 5.75 times more likely to have an autism disorder than those who had fathers under 30. Another Israeli study suggested that the risk of schizophrenia in children is almost double if the father is in his late 40s.
Prof Sheena Lewis, a consultant in reproductive medicine at Queen's University Belfast, said that as men get older their sperm DNA becomes more fragmented. By the time a man is 50, the cells that create a man’s sperm have replicated up to 800 times, creating many possibilities for error.

According to Prof Lewis: The impact of the father smoking is even worse than the mother smoking (you can't repair damage caused in sperm DNA) Viagra can affect fertility by causing the sperm to travel too fast Cannabis us slows sperm function, resulting in a reduction in fertility She also warns about the damaging impact of modern lifestyle and environmental factors. http://www.vhi.ie/news/n250607b.jsp

"It makes sense that the mutations causing these diseases would occur more frequently in older men, and indeed that's what we saw for Apert syndrome," says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins.
Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35. Until now, the only evidence for paternal age effects has come from determining how many children with these diseases are born to fathers of various ages.
To obtain the first genetic explanation for these effects, the scientists studied sperm from about 60 men of various ages and looked for two genetic changes responsible for 99 percent of the cases of Apert syndrome. They found that men over 50 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations were not more common in blood samples as men aged.
The scientists say it's likely that the number of cell divisions that go into making a sperm plays a large role in the link between Apert syndrome and paternal age, and represents a fundamental difference between how aging egg and sperm can impact the health of a child.
"In the men we studied, these mutations had not been inherited, but rather collected over time in the reservoir of primitive cells that become sperm," says first author Rivka Glaser, a graduate student in human genetics at the Johns Hopkins School of Medicine.
Cells that mature into eggs are essentially frozen in time from puberty until the time the egg is signaled to develop. Because of the stage at which they are "frozen," the most likely error in an egg is to have an abnormal partitioning of chromosomes, producing an egg with an extra copy or a missing copy, Glaser says. For example, in Down syndrome, an extra copy of chromosome 21 is inherited from the mother.
Sperm, on the other hand, are continually produced throughout a male's lifetime from a reservoir of primitive cells. These primitive cells, like other kinds of so-called stem cells, can either replicate themselves or take a step closer to becoming a sperm, a process called differentiation. All told, these cells divide every 21 days after puberty, and at each cell division the opportunity exists for an error in copying the DNA.
"Literally hundreds of millions of sperm are made in each batch, so in most cases there are still many normal sperm available," says Jabs, also a professor of pediatrics. Their study showed that "high levels" of mutations among men who had no children with Apert syndrome amounted to roughly 3 sperm with the mutation among 100,000 sperm.
If an error is made in any of the steps toward becoming a sperm, the only cells affected are the resulting sperm for that batch. However, if an error appears in a primitive cell as it replicates itself and the mistake isn't fixed, the mutation will continue to be passed on to all of its progeny, including subsequent primitive cells and other batches of semen.
As men age, more of these primitive cells have collected mutations that cause Apert syndrome, leading to more sperm with the mutations in each batch of semen, the scientists suggest. The risk of having a child with Apert is about six times higher for a man age 52 than for someone who's 27.
Authors on the study are Glaser, Jabs, and Rebecca Schulman, of Johns Hopkins School of Medicine, and Karl Broman, of the Johns Hopkins Bloomberg School of Public Health.
It is curious that although sperm have been around since the beginning of time, we know so little about what is in them, and what makes them tick, er, swim. So scientists spend a lot of their waking hours trying to compare the structure and content of the proteins of sperm in various species, in order to understand their evolution and origin. For instance, the mutated DNA in the genes of the sperm of older fathers is believed to cause many genetic diseases. It is almost as if a man’s biological clock accelerates mutation in sperm cells in his early ’30s.



So is the following statement true?



"Almost all cases [of spontaneous mutations] happen in the mother and are transmitted by the mother," he said, adding that the trait for Down is transmitted at the moment of conception. The trait is not hereditary in the same sense a "disease gene" is transmitted from one generation to the next.
As people age, their genes increasingly acquire mutations that are not fixed through DNA repair mechanisms. That's why a spontaneous strike can lead to Down syndrome. And that is also why autism can similarly occur through CNVs, Dr. Wigler said.
"The older the mother, the more likely she has acquired spontaneous mutations" in her chromosomes, and will transmit them at conception, Dr. Wigler said. Less frequently, but just as likely, Dr. Wigler said, fathers can transmit autism traits as well.

Is there a scientist that will debate this statement?

Probably not, but it is not true! Research has found that older mothers are not main the source of new mutations even in Down Syndrome. CNVs and chromosomal translocations are not the same thing.


But you don't have to carry a genetic disease to pass one on — the trouble can start in your testicles. There, sperm-generating cells divide about 23 times a year, in the process slowly accumulating copying errors.
Older fathers are more likely to have children with achondroplasia (dwarfism) and several other conditions caused by spelling errors in the DNA. So for a man, the older you get, the less your child's genetic endowment will resemble your own.
For women, aging isn't as likely to lead to spelling errors because we make no new eggs after we're born. But that leads to other problems. The million or so we begin life with die at a rate of about 30 a day, and as the remaining eggs age, they get less adept at one of their critical jobs — dividing their 46 chromosomes in half. Eggs don't do this until after they're penetrated by a sperm.


The 'Down' side of dad getting older


Although research has shown that babies born to older mothers are at greater risk of having genetic abnormalities such as Down syndrome, it's long been thought that the mother's age was the sole determining risk factor. A new study by researchers at the Columbia Presbyterian Medical Center at NewYork-Presbyterian Hospital shows that the father's age also plays an important risk-determining role in the incidence of this genetic abnormality.


The report appears in the June 2003 issue of the Journal of Urology. According to the study's author, Harry Fisch, MD, director of the Male Reproductive Center at Columbia Presbyterian Medical Center and associate clinical professor of Urology at Columbia University College of Physicians & Surgeons, the findings "not only add to our knowledge about the incidence of Down syndrome, but also may represent a paradigm for other genetic abnormalities in the children of older fathers. Considering that the population of parents in the U.S. is older than ever before, the paternal age effect is significant and should be addressed during prenatal counseling. Couples preparing for family planning need to be aware that advanced parental age may not only result in increasing difficulties with fertility for the parents, but also that children born to older fathers may have a higher risk of genetic abnormalities."
Down syndrome, or trisomy 21, is a common congenital abnormality that affects 1 out of 800 to 1000 newborns. The influence of maternal age on increased risk of this most common nonlethal trisomy disorder has been known since the 1930's. The rate of Down syndrome has been shown to increase in mothers older than age 35. Until now, however, the effect of paternal age has been controversial. Various large U.S. and European epidemiological studies of the disorder have shown no influence between paternal age and Down syndrome, while smaller studies have demonstrated conflicting results. "In light of this, in addition to the fact that there is an increasing number of older couples having children, we decided to examine a very large number of cases in order to provide definitive evidence as to whether or not paternal age is indeed a risk factor for Down syndrome," explains Dr Fisch.

The number of cases evaluated in the Columbia study -- 3419 -- is the largest number of Down syndrome cases ever examined for the effect of parental age. The investigators looked at the number of babies born to mothers over age 35 between 1983 and 1997 in New York State, which witnessed a dramatic rise in births to this parental age group. Over this study period, there was an increase of 111 percent and 60 percent, respectively, in the number of mothers and fathers over age 35. Data on the incidence of Down syndrome was obtained from the New York State Department of Health Congenital Malformations Registry and was then compared to parental age for this period.
The incidence of babies born to older mothers increased during the study years. In 1983, 8 percent of all births were to women 35 years of age and older, compared with 17 percent of all births in 1997. Births to mothers older than 40 years of age increased approximately 2.5 times between 1983 and 1997. The greatest change in this time period occurred in both maternal and paternal ages greater than 40 years with a 178 percent and 73 percent increase from 1983 to 1997, respectively.
Dr Fisch and his colleagues found that the rate of Down syndrome steadily increased with advancing paternal age for the maternal age group of 35 to 39 years. The greatest increase, however, was seen in the maternal age group of 40 years and older with increasing paternal age. "The rate of Down syndrome for both maternal and paternal age greater than 40 years is approximately 60 per 10,000 births, which is a six-fold increase compared with maternal and paternal ages less than 35 years of age. In this age group, the paternal contribution to Down syndrome was 50 percent. Men over age 40 were twice as likely to have a Down syndrome child than men less than 20 years old," notes Dr Fisch.
"Since older women tend to be have children with older men, the increased incidence of this genetic abnormality in women older than 35 is likely to be the result of a combination effect of maternal and paternal age, rather than the result of maternal age only. This interaction would explain the dramatic increase in Down syndrome that is seen in women older than 35," he points out.
This finding of the paternal age influence on Down syndrome suggests that there is a sperm contribution to the trisomy; increased paternal age may lead to an increased frequency of chromosome abnormalities in sperm, according to Dr Fisch. "Our finding of a paternal contribution to trisomy 21 indicates a structural chromosomal risk than had not previously been appreciated. It is our belief that increased paternal age, as well as maternal age, may be responsible for a wide variety of health problems in children. This effect has been underestimated and warrants further research. The reduced semen quality in older men may increase the risk of genetic abnormalities in their children and some of our current research is seeking to evaluate ways to reduce this risk," he concludes.