Regulation of somatic aging by the hyperactive germline

The National Institute on Aging awarded the University of New Orleans $149,000 on May 1, 2026, under the Aging Research program (CFDA 93.866) to investigate mechanistic links between elevated reproductive activity and reduced lifespan in Caenorhabditis elegans.

The research addresses a gap in understanding how increased reproduction influences somatic aging by studying mated worms with hyperactive germlines. The investigator recently identified hedgehog signaling in mated worms as the first known germline-to-soma pro-aging signal in any model organism; this award funds two specific aims to understand downstream mechanisms. Aim 1 will identify somatic transcriptional targets of germline-derived hedgehog signaling that mediate lifespan shortening. Aim 2 will examine how germline hyperactivity influences lipid metabolism and determine whether mating-induced fat loss in mated worms reflects passive resource reallocation or active lipid-based signaling between germline and soma. The research holds potential to uncover conserved mechanisms of lipid metabolism, germline-soma communication, fertility maintenance, and lifespan extension across animal species, including humans.

Performance runs from May 1, 2026, through April 30, 2028, at the University of New Orleans in New Orleans, Louisiana.

Abstract

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.