Meiotic dysfunction accelerates somatic aging in Caenorhabditis elegans

Abstract

An expanding body of evidence, from studies in model organisms to human clinical data, reveals that reproductive health influences organismal aging. However, the impact of germline integrity on somatic aging is poorly understood. Moreover, assessing the causal relationship of such an impact is challenging to address in human and vertebrate models. Here, we demonstrate that disruption of meiosis, a germline restricted process, shortened lifespan, impaired individual aspects of healthspan, and accelerated somatic aging in Caenorhabditis elegans. Young meiotic mutants exhibited transcriptional profiles that showed remarkable overlap with the transcriptomes of old worms and shared similarities with transcriptomes of aging human tissues as well. We found that meiosis dysfunction caused increased expression of functionally relevant longevity determinants whose inactivation enhanced the lifespan of normal animals. Further, meiotic mutants manifested destabilized protein homeostasis and enhanced proteasomal activity partially rescued the associated lifespan defects. Our study demonstrates a role for meiotic integrity in controlling somatic aging and reveals proteostasis control as a potential mechanism through which germline status impacts overall organismal health.

Epigenetic clocks and female fertility timeline: A new approach to an old issue?

“…One of the most stimulating theories supports a new concept of age-related infertility as the first sign of an “accelerated aging disease” ( Llarena and Hine, 2021 ; Loose et al, 2022 ). In other words, ovaries could be the first compartment to show signs of a general process of accelerated aging.…”

Effects of reactive oxygen species and mitochondrial dysfunction on reproductive aging

“…Healthcare advances and the distribution of vaccines have contributed to the increase in life expectancy from 35 years in the 18th century to 72.6 years today (Nakamura et al, 2017;Mansouri Torghabeh et al, 2022). Based on numerous observations, it has been hypothesized that the poor quality of reproductive cells can result in accelerated aging and a shorter healthspan (Loose et al, 2022). The state of the reproductive system is not only essential for fertility, but also for overall health.…”

“…Reproductive aging is a universal developmental process conserved across species coinciding with age-related fertility depletion and decline of gamete quality, culminating in infertility and deleterious consequences on the offspring (Drori and Folman, 1976;Drewry et al, 2011;Archie et al, 2014;Sinha and Rae, 2014). Reproduction is an energy-costly undertaking that profoundly impacts on multiple individual characteristics at molecular, cellular, and endocrine levels (Loose et al, 2022;Secomandi et al, 2022). Nevertheless, reproductive fitness also offers notable physiological benefits.…”