Genetics: Parental Influence

Retrospective studies have reported that older parentage can adversely affect aging in offspring, with some studies reporting stronger contributions from either maternal or paternal sources. For example, in a report by Leonid Gavrilov and colleagues in 1997, analysis of records of European aristocracy revealed that female offspring of older fathers had a significantly reduced life span. Because the effect was related to a paternal source and only influenced female offspring, mutations inherited via the paternal X-chromosome were suspected. As reviewed by Juan Tarin and colleagues in 1998, there are also several diseases associated with older paternal age, including Wilms' tumor, Apert's syndrome, and Marfan's syndrome, among others. Gwen McIntosh, in a 1995 study that controlled for maternal age and known chromosomal abnormalities, found an increased incidence of birth defects as a function of increasing paternal age. Older paternal age has also recently been associated with an increased incidence of prostate cancer and brain cancer. It has been conjectured in the copy error hypothesis of L. S. Penrose that spermatozoa are more prone to mutations than oocytes, due to the larger number of divisions they have undergone with age. A review by Crow reports that DNA duplication during gametogenesis is the period when mutations most readily occur.

Aging of female oocyte stocks can also have an effect on the appearance of disease in adult offspring. One of the more familiar circumstances is an aberration in chromosome number, known as aneuploidy, which can cause severe developmental problems and compromise life span. Many cases are manifested as trisomy, where three copies of a chromosome (instead of the normal two) occur with increased frequency with advancing maternal age. For example, Down syndrome (trisomy 21), which results in short stature, mental deficiencies, physiological problems, and a shortened life span, is caused by maternal problems in chromosome separation (nondisjunction), resulting in the appearance of an extra chromosome 21. Trisomy of other chromosomes also occurs in lesser frequencies in newborns, such as chromosome 18 (Edwards' syndrome) and chromosome 13 (Patau's syndrome). In the majority of cases, nondisjunction of maternal origin appears to be responsible for the trisomic condition, although a small percentage of cases involve the paternal source.