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: 2.02). 02/2011; 49(2):53-65. DOI: 10.1002/dvg.20694
Source: PubMed


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.

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    • "It is known that the germline and somatic reproductive system can signal to the rest of the soma to regulate lifespan through steroid hormones and the insulin signaling pathway (Hsin & Kenyon, 1999; Arantes-Oliveira et al., 2002; Yamawaki et al., 2010), and it is possible that EGR-1 is responding to these signals. As reproductive aging occurs relatively early in the worm lifespan (Luo & Murphy, 2011), it is likely that changes in signals from the germline represent an early molecular event in aging and could cause changes in many downstream genes in the soma. The fact that loss of egr-1 fully suppresses the longevity of germlineless mutants adds further evidence that egr-1 acts downstream of the germline to promote longevity. "
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    • "Some systems may change slowly, while others decline rapidly, and some may even show periods of increased function (Spirduso et al., 2005). Despite the extensive variability both between species, and within individuals, several tissues exhibit physiological senescence in both invertebrates and mammals, including a decline in muscle strength (Nair, 2005; Augustin and Partridge, 2009; Demontis and Perrimon, 2010), immune response (Hoffmann, 2003; Flajnik and Du Pasquier, 2004), stress resistance (Service et al., 1985; Rose, 1999; Murakami, 2006), reproduction (te Velde and Pearson, 2002; Novoseltsev et al., 2005; Tatar, 2010; Luo and Murphy, 2011), and cognition (Horiuchi and Saitoe, 2005; Grady, 2008). "
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    Frontiers in Physiology 04/2012; 3:106. DOI:10.3389/fphys.2012.00106 · 3.53 Impact Factor
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    ABSTRACT: Author Summary Dynamic response to changing conditions in the environment is an essential property of all biological systems. Whereas extensive research over the last several decades has elucidated numerous molecular responses to environmental stress, there is much less known how these translate into organismal-level responses. Two types of modeling approaches are often used to bridge this gap. Fine-grained models seek to explain phenomena as resulting from interactions of large numbers of individual components. This approach demands a highly detailed knowledge of the underlying molecular mechanisms and has an inherent difficulty in crossing spatial scales and organizational hierarchies. As an alternative, here we present a macro-level model of reproduction in C. elegans that uses fundamental engineering principles, together with a limited set of experimentally derived facts, to provide quantitatively accurate predictions of performance under a range of physiologically relevant conditions. One important finding is that individuals within a population display considerable heterogeneity in their response to heat stress. This could be a reflection of different strategies for coping with the ever-changing environment. Our study further demonstrates that dynamic behaviors of systems may be determined by a small number of key components that lead to the emergence of organismal phenomena.
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