Molecular basis of reproductive senescence: insights from model organisms

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.

Section: Introductionmentioning

confidence: 99%

Reproductive Aging in Caenorhabditis elegans: From Molecules to Ecology

Scharf

Pohl

Egan

et al. 2021

“…As more women opt to have children later in life, addressing the issue of female reproductive aging has become increasingly important. Recently, the nematode Caenorhabditis elegans has been developed as a model to study reproductive capacity decline with age ( Hughes et al, 2007 ; Andux and Ellis, 2008 ; Luo et al, 2010 ; Quesada-Candela et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Aging Negatively Impacts DNA Repair and Bivalent Formation in the C. elegans Germ Line

Raices

Bowman

Smolikove

et al. 2021

Self Cite

Defects in crossover (CO) formation during meiosis are a leading cause of birth defects, embryonic lethality, and infertility. In a wide range of species, maternal aging increases aneuploidy and decreases oocyte quality. In C. elegans which produce oocytes throughout the first half of adulthood, aging both decreases oocytes quality and increases meiotic errors. Phenotypes of mutations in genes encoding double-strand break (DSB)-associated proteins get more severe with maternal age suggesting that early meiosis reflects a particularly sensitive node during reproductive aging in the worm. We observed that aging has a direct effect on the integrity of C. elegans meiotic CO formation, as observed by an increase of univalent chromosomes and fusions at diakinesis, with a considerable increase starting at 4 days. We also characterize the possible causes for the age-related changes in CO formation by analyzing both steady-state levels and kinetics of the ssDNA binding proteins RPA-1 and RAD-51. Profound reductions in numbers of both RPA-1 and RAD-51 foci suggests that both DSB formation and early meiotic repair are compromised in aging worms. Using laser microirradiation and γ-irradiation to induce exogenous damage, we show specifically that recruitment of these homologous recombination proteins is altered. Repair defects can be seen in two-and-one-half day-old adults making the loss of germline repair capacity among the earliest aging phenotypes in the worm.

“…Stress during early life has also been associated with shorter telomeres and mitochondrial inefficiency (Casagrande et al, 2020; but see Brown et al, 2021). Drosophila (Drosophila melanogaster) reared on a poor diet show a higher rate of germline stem cell decline due to changes in insulin signaling (Hsu and Drummond-Barbosa, 2009), which is linked to reproductive senescence (Quesada-Candela et al, 2021). Linking physiological process with late-life fitness in natural conditions will be critical to understand the mechanisms of senescence.…”

Section: Discussionmentioning

confidence: 99%

Do Early-Life Conditions Drive Variation in Senescence of Female Bighorn Sheep?

Pigeon

Landes

Festa‐Bianchet

et al. 2021

The rate of senescence may vary among individuals of a species according to individual life histories and environmental conditions. According to the principle of allocation, changes in mortality driven by environmental conditions influence how organisms allocate resources among costly functions. In several vertebrates, environmental conditions during early life impose trade-offs in allocation between early reproduction and maintenance. The effects of conditions experienced during early life on senescence, however, remain poorly documented in wild populations. We examined how several early-life environmental conditions affected reproductive and survival senescence in wild bighorn sheep. We found long-term effects of high population density at birth, precipitations during the winter before birth, and temperature during the winter following birth that decreased survival after 7 years of age. High temperature during the first summer and autumn of life and high Pacific decadal oscillation decreased reproductive success at old ages. However, harsh early-life environment did not influence the rate of senescence in either survival or reproduction. Contrary to our expectation, we found no trade-off between reproductive allocation prior to senescence and senescence. Our results do show that early-life environmental conditions are important drivers of later survival and reproductive success and contribute to intra-specific variation in late-life fitness, but not aging patterns. These conditions should therefore be considered when studying the mechanisms of senescence and the determinants of variation in both survival and reproductive senescence at older ages.