Every organism ages, and during aging, the function of the organism deteriorates including behaviors such as locomotion, mating and feeding. Many studies have focused on the molecular signaling, which can extend or shorten lifespan. But little is known about why a specific behavior deteriorates during aging. In our study, we are trying to figure out the mechanism by which C.elegans males mating behavior declines during aging. Through mating potency analyses, we find that wild-type C. elegans virgin males' mating behavior begins to decline at day 3 of adulthood. 80%, 70% and 40% males can mate at day 1, day 2 and day 3, respectively. Sir-2.1 null mutant males cannot mate well from day 2. 75% and 10%
sir-2.1 null males can mate at day 1 and day 2, respectively. Since caloric restriction can extend the lifespan of C. elegans, we hypothesize that starvation can also prolong the mating potency of males. Indeed, when we starve L4 wild-type males for 20hrs and then re-fed them, those males mating potency can be prolonged. Then we ask if the caloric restriction works through SIR-2.1 to prolong mating potency. To our surprise, caloric restriction during L4 can actually rescue the
sir-2.1 null males mating potency at day 2. Cycloheximide – a translational inhibitor can also extend the lifespan of C. elegans, so we check if cycloheximide can affect mating potency. It can prolong the mating potency of wild type, but not
sir-2.1 null mutant males. Because the neuromuscular mating circuit of C. elegans males is mainly regulated by ACh signaling. We check the sensitivity of acetylcholine signaling during aging by exposing males to ACh agonist such as levamisole and arecoline, we find that males become more sensitive to Ach agonist when they are aged, which is a possible explanation for why aged males cannot mate well. Indeed, males that have decreased Ach signaling due to having one copy of functional ACh receptors genes
unc-29,
acr-16,
acr-18 and
gar-3, can mate better at day 3 than wild type. For
sir-2.1 null mutant males, we find that they are more sensitive to ARE than age-matched
him-5 males, which is consistent with their accelerated decline in mating behavior. Considering that all three factors that can affect mating potency can down-regulate gene expression: 1. SIR-2.1 is a histone deacetylase histone that can promote the chromosome condensation, thus attenuate gene transcription; 2. Starvation can reduce translation; And 3. Cycloheximide can inhibit elongation process during translation. We hypothesize that during aging more Ach receptors are expressed so that males become more sensitive to Ach agonist. And SIR-2.1, starvation, or cycloheximide can down-regulate the Ach receptors expression so that aged wild type males can mate more efficiently.