Delayed parenthood in developed countries means more old dads. Who cares you ask? You should, as this trend doesn’t just increase early morning traffic at Starbucks, it can also increase the incidence of autism, bipolar disorders, schizophrenia, some forms of cancer, or other disorders that accompany the offspring of older fathers. Way to go Dad; we hope that four year globetrotting expedition after college to “find yourself” really paid off.
Though increased incidence of various disorders had already been correlated with advanced paternal age, the mechanism behind this effect is not known. To address this, a team of researchers from the University of Utah School of Medicine and the Howard Hughes Medical Institute investigated DNA methylation in mature human sperm by comparing the sperm methylome of two samples collected from 9 to 19 years apart from each of 17 donors.
When the donors were older, sperm showed the following characteristics:
- global hypermethylation
- strong regional hypomethylation (total of 110 genes)
- most hypomethylated sites are near regions of nucleosome retention sites in mature sperm
- many alterations are in regions of the genome thought to contribute to conditions with increased incidence in the offspring of older fathers
The authors are careful not to overstate their results. They acknowledge that they are identifying a correlation of an age-associated methylation profile change with disorders known to occur in the offspring of older males, but they do not claim to establish a causative relationship. They explicitly mention the limitations of their methods and use alternate methods to validate many of their results.
Despite these limitations, the authors believe that this work is “the first direct evidence suggesting the plausibility of epigenetic alterations in the sperm of aged fathers influencing, or even causing, disease in the offspring.”
Check out all the details in PLoS Genetics, July 2014