Metabolic Rate and Oxygen Radical Levels Increase But Radical Generation Rate Decreases with Male Age in Drosophila melanogaster Sperm

Abstract

Oxidative damage increases with age in a variety of cell types, including sperm, which are particularly susceptible to attack by reactive oxygen species (ROS). While mitochondrial respiration is the main source of cellular ROS, the relationship between the rates of aerobic metabolism and ROS production, and how this relationship may be affected by age, both in sperm and in other cell types, is unclear. Here, we investigate in Drosophila melanogaster sperm, the effects of male age on (i) the level of hydrogen peroxide in the mitochondria, using a transgenic H2O2 reporter line; (ii) the in situ rate of non-H2O2 ROS production, using a novel biophysical method; and (iii) metabolic rate, using fluorescent lifetime imaging microscopy. Sperm from older males had higher mitochondrial ROS levels and a higher metabolic rate but produced ROS at a lower rate. In comparison, a somatic tissue, the gut epithelium, also showed an age-related increase in mitochondrial ROS levels but a decrease in metabolic rate. These results support the idea of a tissue-specific optimal rate of aerobic respiration balancing the production and removal of ROS, with aging causing a shift away from this optimum and leading to increased ROS accumulation. Our findings also support the view that pathways of germline and somatic aging can be uncoupled, which may have implications for male infertility treatments.