Article

Caenorhabditis elegans reproductive aging: Regulation and underlying mechanisms

Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jeresy, USA.
genesis (Impact Factor: 2.04). 02/2011; 49(2):53-65. DOI: 10.1002/dvg.20694
Source: PubMed

ABSTRACT Female reproductive decline is one of the first aging phenotypes in humans, manifested in increasing rates of infertility, miscarriage, and birth defects in children of mothers over 35. Recently, Caenorhabditis elegans (C. elegans) has been developed as a model to study reproductive aging, and several studies have advanced our knowledge of reproductive aging regulation in this organism. In this review, we describe our current understanding of reproductive cessation in C. elegans, including the relationship between oocyte quality, ovulation rate, progeny number, and reproductive span. We then discuss possible mechanisms of oocyte quality control, and provide an overview of the signaling pathways currently identified to be involved in reproductive span regulation in C. elegans. Finally, we extend the relevance of C. elegans reproductive aging studies to the issue of human female reproductive decline, and we discuss ideas concerning the relationship between reproductive aging and somatic longevity.

Full-text

Available from: Coleen Murphy, Apr 27, 2015
1 Follower
 · 
183 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interactions between the germline and the soma help optimize reproductive success. We discovered a new phenomenon linking reproductive status to longevity: in both hermaphroditic and gonochoristic Caenorhabditis, mating leads to female shrinking and death, compressing post-reproductive lifespan. Male sperm induces germline- and DAF-9/DAF-12-dependent shrinking, osmotic stress susceptibility, and subsequent lifespan decrease, while seminal fluid induces DAF-16-dependent lifespan decrease and fat loss. Our study provides new insight into the communication between males and the female germline and soma to regulate reproduction and longevity, revealing a high-reproduction/low lifespan state induced by mating. Post-mating somatic collapse may be an example of the sexually antagonistic influence that males in many species exert on female behavior to maximize their own reproductive success.
    Science 12/2013; 343(6170). DOI:10.1126/science.1242958
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with a large number of both phenotypic and molecular changes, but for most of these, it is not known whether these changes are detrimental, neutral, or protective. We have identified a conserved Caenorhabditis elegans GATA transcription factor/MTA-1 homolog egr-1 (lin-40) that extends lifespan and promotes resistance to heat and UV stress when overexpressed. Expression of egr-1 increases with age, suggesting that it may promote survival during normal aging. This increase in expression is dependent on the presence of the germline, raising the possibility that egr-1 expression is regulated by signals from the germline. In addition, loss of egr-1 suppresses the long lifespan of insulin receptor daf-2 mutants. The DAF-16 FOXO transcription factor is required for the increased stress resistance of egr-1 overexpression mutants, and egr-1 is necessary for the proper regulation of sod-3 (a reporter for DAF-16 activity). These results indicate that egr-1 acts within the insulin signaling pathway. egr-1 can also activate the expression of its paralog egl-27, another factor known to extend lifespan and increase stress resistance, suggesting that the two genes act in a common program to promote survival. These results identify egr-1 as part of a longevity-promoting circuit that changes with age in a manner that is beneficial for the lifespan of the organism.
    Aging cell 12/2013; DOI:10.1111/acel.12179
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In C. elegans, mutations in the conserved insulin/IGF-1 signaling (IIS) pathway lead to a robust extension in lifespan, improved late life health, and protection from age-related disease. These effects are mediated by the FoxO transcription factor DAF-16 which lies downstream of the IIS kinase cascade. Identifying and functionally testing DAF-16 target genes has been a focal point of ageing research for the last 10 years. Here, I review the recent advances in identifying and understanding IIS/DAF-16 targets. These studies continue to reveal the intricate nature of the IIS/DAF-16 gene regulation network and are helping us to understand the mechanisms that control lifespan. Ageing and age related disease is an area of intense public interest, and the biochemical characterization of the genes involved will be critical for identifying drugs to improve the health of our ageing population.
    Biogerontology 08/2014; 16(2). DOI:10.1007/s10522-014-9527-y