The paternal age effect: a multifaceted phenomenon.

Birth rates for older fathers have increased 30% since 1980. When combined with the increased risk for genetic and multifactorial disorders in children conceived by older fathers, paternal age has become an important health issue for modern society. Laboratory research in this area has been minimal, perhaps because of significant experimental barriers, not the least of which is inadequate access to fresh, disease-free human testicular tissue. Regardless, progress has been made and intriguing models supported by experimental evidence have been proposed. The putative mechanisms range from reduced DNA repair activity, leading to increased mutagenesis, to positive selection of germ cells harboring specific disease-causing mutations. There remain many important venues for research in this increasingly relevant phenomenon that impacts future generations.