I cite a sampling of research studies here related to the quality of human male semen as a function of age and the possible impacts of dietary supplementation. This topic is increasingly important because of the trend in our society for men to have children at more advanced ages.
First of all, there is a general inverse relationship between sperm quality and age of the donor. A study report on The effects of male age on sperm DNA damage in healthy non-smokers looked at 80 non-smoking men (mean age: 46.4 years, range: 22–80 years). The researchers concluded: “Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.” Being both old and a coffee drinker this would be bad news for me if I were planning to have additional children, which I am not.
Another study Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm brings additional bad news for older would-be fathers. The study looked at 97 nonsmoking men aged 22-80 years. The researchers report: “Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos.”
Implicated in deterioration of sperm quality are some of the same factors that affect cell health and drive aging, for example Oxidative Damage and Cell DNA Damage. One study entitled Antioxidant intake is associated with semen quality in healthy men based on study of sperm from 97 men reports: “–, higher antioxidant intake was associated with higher sperm numbers and motility.” For another study of 114 subjects (60 infertile patients and 54 age-matched healthy workers), the researchers report: “Data from this study thus indicate that oxidative damage to sperm DNA may be important in the etiology of male infertility – .“ This review article looks more broadly at the relationship between oxidative stress and male infertility. “ — oxygen ions, free radicals and peroxides (ROS) — produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus.”
A very recent study looked at the Effect of parental age at birth on the accumulation of deficits, frailty and survival in older adults. “Data was collected on individuals aged 65 (or greater) using a Self-Assessed Risk Factor Questionnaire and screening interview. In this secondary analysis, 5112 participants had complete data for parental age, frailty status and 10-year survival. Parental age was divided into three groups, with cut-offs at 25 and 45 for fathers and at 25 and 40 for mothers. Frailty was defined by an index of deficits.” The researchers reported “There was no effect of maternal or paternal age on survival for either sons or daughters. Similarly, there was no association between parental age and subject frailty in old age.” This time the news was good. On the other hand since all the participants had already made it to age 65, the study does not tell us what effect parental age at time of birth might have on survival to 65.
The activities of DNA repair mechanisms seem to be age-dependent. This study Age-Dependent Usage of Double-Strand-Break Repair Pathways looks at DNA repair in the premeiotic germ cells of Drosophila (fruit flies) as a function of age. The results suggest that at least one repair pathway gets more active with age “We used Rr3, a repair reporter system in Drosophila to show that the relative usage of DSB repair mechanisms can change substantially as an organism ages. Homologous repair increased linearly in the male germline from 14% in young individuals to more than 60% in old ones, whereas two other pathways showed a corresponding decrease. Furthermore, the proportion of longer conversion tracts (>156 bp) also increased nearly 2-fold as the flies aged.” I speculate that a similar situation exists for humans: the older the person the more there is a need for repair and actual repair of germline cells.
Among the most widely recognized genetic disorders is Aneuploidy, a condition where there are missing or extra chromosomes. Testing for aneuploidy may be warranted for men with a serious record of infertility or where his mate has experienced unexplained recurrent pregnancy loss(ref).
This study investigated the impact of supplementation by zinc, folate, vitamin C, vitamin E and beta-carotene on aneuploidy using sperm samples from 89 healthy, non-smoking men. Interestingly, the researchers concluded: “Men with high folate intake had lower overall frequencies of several types of aneuploid sperm.” There did not seem to be a correlation of use of the other supplements with aneuploidy.
The research literature related to male fertility is extensive and growing and the nine citations above just scratch the surface. The most obvious implications for normal older men planning to have children are 1. Protect against oxidative stress and cell DNA damage. See the protective firewalls for the Oxidative Damage and the Cell DNA Damage theories of aging, 2. Include folic acid in your supplement regimen. And one more point: 3. Keep yourself young; in today’s world having a father around can be very useful until a child is 30 or older.
I will return to this topic it at a later time. It is bound to become more important when extraordinary longevity becomes possible and there will be a demand for interventions that make it possible, safe and easy for a man to father children at the age of 100, 150 or later.