Regulation of somatic aging by the hyperactive germline

The trade-off between reproduction and somatic longevity has been observed in animals across the evolutionary spectrum, suggesting the existence of conserved regulators of these two processes. However, most studies have predominantly focused on models with germline removal or limited reproductive capacity, leaving a critical gap in our understanding of how increased reproduction influences somatic aging. This project aims to address that gap by investigating the mechanistic links between elevated reproductive activity and reduced lifespan using mated Caenorhabditis elegans with hyperactive germlines. We recently identified Hedgehog signaling in mated worms as the first known germline-to-soma pro-aging signal in any model organism. Yet, the downstream somatic mechanisms remain largely unknown. In Aim 1, we will identify the somatic transcriptional targets of germline-derived Hedgehog signaling that mediate lifespan shortening. Given that mated worms show pronounced somatic fat loss, Aim 2 will examine how germline hyperactivity influences lipid metabolism and determine whether mating-induced fat loss reflects passive resource reallocation or active lipid-based signaling between the germline and soma. Together, we anticipate that these investigations will offer unprecedented understanding of how increased reproduction influences somatic health and longevity. Due to the universality of the reproduction-longevity trade-off, this research holds strong potential to uncover novel and conserved mechanisms of lipid metabolism, germline-soma communications, fertility maintenance, and lifespan extension in all animals, including humans. Project Number: 1R03AG101241-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Cheng Shi | Institution: UNIVERSITY OF NEW ORLEANS, NEW ORLEANS, LA | Award Amount: $149,000 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 CDB-H (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11355794