| dc.description.abstract | Aging has been a subject of interest throughout history. Scientific studies have focused on lifespan regulation, but ignored many other aspects of aging such as behavioral decline. Research using the model organism C. elegans has contributed significantly to the aging field. In this dissertation, I used C. elegans males to determine the molecular mechanisms of behavioral deterioration during aging. Through mating potency assays, I found that the mating behavior of C. elegans declines at early
adulthood, as the mating potency of 3-day-old wild-type males is significantly lower than 1-day-old males. Meanwhile, using both pharmacological tests and calcium imaging, I showed that the excitability of the mating circuit increased during early adulthood. This is consistent with the observation that old males exhibit reduced control over their ability to mate.
Caloric restriction is an efficient non-genetic intervention to increase lifespan. I demonstrated here that it also improves mating behavior in 3-day-old males, possibly through reducing the excitability of the mating circuitry by up-regulation of potassium channels and additional metabolic enzymes.
To explore the relationship between metabolic status and behavioral deterioration, I characterized the dynamics of male mating deterioration in males containing a deletion in the metabolism-regulator sir-2.1. sir-2.1 encodes a NAD^(+) dependent histone deacetylase, which might be involved in regulating aging. I discovered that sir-2.1(0) males have a premature decline in mating potency and an accelerated increase in the excitability of the mating circuitry. Direct mating behavior observations indicated that a significant proportion of 2-day-old sir-2.1(0) males cannot transfer their sperm into their hermaphrodite mates. Through Ca^(2+) imaging, I found that the genital sex muscles are hyper-contracted during sperm transfer. This hyper-contraction blocks the vas deferens
and obstructs sperm release. Furthermore, through qPCR, measurements of metabolites, and diet supplementation, I found that the potentially enhanced catabolism in 1-day-old sir-2.1(0) and 2-day-old wild-type males generates excess reactive oxygen species (ROS). ROS increases the excitability of the mating circuitry and leads to the mating potency decline in subsequent days. Meanwhile, anabolic processes such as gluconeogenesis/glyceroneogenesis are also elevated. These processes shunt pyruvate from oxidative processes to lipid synthesis, and serve as a potential compensatory mechanism to reduce energy and ROS production.
In conclusion, I demonstrated that a complex behavior in C. elegans deteriorated during early aging due to the physiological state change, which is possibly caused by ROS induced by both metabolic and stress-response alteration. | en |
