It is advanced paternal age or maternal grandfather's age at the mother's conception that can lead to genetic disorders in offspring

http://www.dana.org/news/cerebrum/detail.aspx?id=1452Deteriorating sperm are associated with dwarfism and other disorders.



In fact, the risk to the offspring goes up steadily with the age of the father after age 24, independent of the age of the mother. By the time the father is over 45, his risk of having a child who will develop schizophrenia is nine times higher than that of a 20-year-old father.





It now appears, however, that it is not older mothers who are more likely to have offspring who become schizophrenic but rather older fathers. Regardless of whether they have a family history of schizophrenia, older fathers confer an increased risk of schizophrenia on their offspring. In fact, the risk to the offspring goes up steadily with the age of the father after age 24, independent of the age of the mother. By the time the father is over 45, his risk of having a child who will develop schizophrenia is nine times higher than that of a 20-year-old father. The most likely reason is that men are constantly developing new sperm. Because the precursors to sperm— spermatocytes—divide every 16 days, by the time a man is 55 years old, almost 1,000 cell divisions have taken place. The opportunity for a copying error in the sperm in which a mutation spreads through the generations of sperm by copying itself is, therefore, relatively high.

The contribution of a father’s increased age could explain a good number of the observations associated with schizophrenia. For instance, although schizophrenia clearly runs in families, it does not do so in a manner consistent with the classical genetics of Gregor Mendel. It can, for instance, appear in families where it has not been seen before. The risk attached to older fathers may be more apparent today. Probably a certain number of older men have always produced children, but having a large pool of older fathers healthy enough to have children in substantial numbers is a new phenomenon.\\






Journal of Epidemiology and Community Health 2006;60:851-853; doi:10.1136/jech.2005.045179
Copyright © 2006 by the BMJ Publishing Group Ltd.
This Article





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SHORT REPORT

Advanced paternal age: How old is too old?
Isabelle Bray, David Gunnell, George Davey Smith

Department of Social Medicine, University of Bristol, UK


Correspondence to:
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


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.



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