Reproductive Aging in Caenorhabditis elegans: From Molecules to Ecology

Abstract

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism Caenorhabditis elegans, hermaphrodites reach a peak of progeny production on day 2 of adulthood and then display a rapid decline; progeny production typically ends by day 8 of adulthood. Since animals typically survive until day 15 of adulthood, there is a substantial post reproductive lifespan. Here we review the molecular and cellular changes that occur during reproductive aging, including reductions in stem cell number and activity, slowing meiotic progression, diminished Notch signaling, and deterioration of germ line and oocyte morphology. Several interventions have been identified that delay reproductive aging, including mutations, drugs and environmental factors such as temperature. The detailed description of reproductive aging coupled with interventions that delay this process have made C. elegans a leading model system to understand the mechanisms that drive reproductive aging. While reproductive aging has dramatic consequences for individual fertility, it also has consequences for the ecology of the population. Population dynamics are driven by birth and death, and reproductive aging is one important factor that influences birth rate. A variety of theories have been advanced to explain why reproductive aging occurs and how it has been sculpted during evolution. Here we summarize these theories and discuss the utility of C. elegans for testing mechanistic and evolutionary models of reproductive aging.

Conserved neuropeptidergic regulation of intestinal integrity in invertebrate models of aging

“…Interestingly, this DAF-28 secretion profile mirrored the reproductive span ( Fig. 4D ) 56,57 , consistent with its function in promoting reproduction 58 .…”

Pollutants corrupt resilience pathways of aging in the nematode C. elegans

“…The capacity of the proteostasis network to resolve misfolded and damaged proteins declines in early adulthood in C. elegans (Ben-Zvi et al, 2009) and causes an age-related increase in protein aggregation manifested in an old age aggregation phenotype. The decline of the proteostasis network is most likely temporally fine-tuned to secure reproduction which peaks on day 2/3 of adulthood under normal condition (Scharf et al, 2021). This conclusion is supported by the observation, that most somatic age-related changes occur after the decline of reproduction (Pickett et al, 2013).…”

Notch signaling in germ line stem cells controls reproductive aging in C. elegans

“…Most aging research focuses on the decline of life support systems that result in death and determine adult lifespan. However, there is growing appreciation that the age-related decline of the reproductive system, which results in infertility, is an important dimension of aging (Scharf et al, 2021). Because female reproduction typically declines well before the maximum adult lifespan, reproductive aging offers the possibility to experimentally investigate an aging organ in the context of a relatively intact animal.…”

“…The nematode worm Caenorhabditis elegans is an experimentally powerful model for reproductive aging that is relevant to mammals (Athar and Templeman, 2022; Scharf et al, 2021). From a fertilized egg, the C. elegans hermaphrodite develops its entire soma and both arms of its reproductive tract, then begins laying eggs at ∼65 hours at 20°C (Byerly et al, 1976).…”

“…A detailed description of the molecular and cellular changes that occur during reproductive aging is important for generating hypotheses about the sequence of events that cause these changes (Scharf et al, 2021). This description is an essential foundation to comprehensively understand how genetic mutations influence this phenotype.…”