C. elegans males display a significant deterioration of mating behavior during 'early aging' prior to the structural dysfunction of neuromuscular circuitry. The mating deterioration is correlated with an increase of the excitability in the male mating circuitry(1). Here, we showed that the mating behavior of males with
sir-2.1 null mutation declines even prematurely compared to that of wild-type males, and the mating circuitry of
sir-2.1(
ok434) is more excitable than that of wild type males. Through Ca2+ imaging in mating males, we demonstrated that the hyper excitation of sex muscles during mating blocks the process of sperm transferring in 2-day-old
sir-2.1(
ok434) males, hence leading to the failure of mating. Furthermore, we illustrated that
sir-2.1(
ok434) males generate more reactive oxygen species (ROS) possibly due to enhanced catabolism in the mating circuits and/or reduced ability to scavenge ROS because of reduced expression of ROS-scavenger genes such as superoxide dismutase
sod-1and glutathione transferase
gsto-1. Meanwhile, we found that artificially increasing ROS stress by feeding males with paraquat elevates the excitability of the mating circuitry and reduces the mating potency. In addition, reducing ROS by feeding males with N-Acetyl Cysteine (NAC), an antioxidant reagent, lowers the excitability of the mating circuitry and improves mating. Taken together, we conclude that SIR-2.1, a histone deacetylase (HDAC) regulates the physiological state of the mating circuitry possibly through regulation of the oxidative stress. Reference: 1.Guo X, Navetta A, Gualberto DG, Garcia LR. Behavioral decay in aging male C. elegans correlates with increased cell excitability. Neurobiol Aging. 2012.