Applied Zoology, Faculty Biology, Technische Universität Dresden, Germany.
J Gerontol A Biol Sci Med Sci. 2020 Nov 13;75(12):2278-2285. doi: 10.1093/gerona/glaa078.
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.
氧化损伤会在多种细胞类型中随年龄的增长而增加，包括精子，其特别容易受到活性氧（ROS）的攻击。虽然线粒体呼吸是细胞 ROS 的主要来源，但有氧代谢率和 ROS 产生率之间的关系，以及这种关系如何随年龄变化，无论是在精子还是其他细胞类型中，都不清楚。在这里，我们在黑腹果蝇的精子中研究了雄性年龄对（i）使用转基因 H2O2 报告系测量的线粒体中过氧化氢水平；（ii）使用新型生物物理方法测量的非 H2O2 ROS 原位产生率；以及（iii）使用荧光寿命成像显微镜测量的代谢率的影响。来自老年雄性的精子具有更高的线粒体 ROS 水平和更高的代谢率，但产生 ROS 的速度较低。相比之下，一种体组织，肠道上皮，也显示出与年龄相关的线粒体 ROS 水平增加，但代谢率下降。这些结果支持了这样一种观点，即有氧呼吸的组织特异性最佳速率可以平衡 ROS 的产生和清除，而衰老会导致这种最佳状态的偏离，并导致 ROS 积累增加。我们的研究结果还支持生殖系和体组织衰老途径可以解耦的观点，这可能对男性不育治疗有影响。
