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Journal List > PLoS Genet > v.3(2); Feb 2007

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PLoS Genet. 2007 February; 3(2): e25.
Published online 2007 February 16. Prepublished online 2006 December 28. doi: 10.1371/journal.pgen.0030025.
PMCID: PMC1797816
Copyright : © 2007 Hughes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Genetic and Pharmacological Factors That Influence Reproductive Aging in Nematodes
Stacie E Hughes,1¤ Kimberley Evason,1 Chengjie Xiong,2 and Kerry Kornfeld1*
1 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, United States of America
2 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Stuart K Kim, Editor
Stanford University, United States of America
* To whom correspondence should be addressed. E-mail: kornfeld/at/wustl.edu
Received July 27, 2006; Accepted December 27, 2006.
Small right arrow pointing to: See "The Role of Mitochondrial DNA Mutations in Mammalian Aging" , e24.
Small right arrow pointing to: See "An Age-Old Problem" , e37.
 
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Abstract
Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed.
Author Summary
In animals, aging is characterized by degenerative changes that progressively diminish the function of tissues and organs. Degenerative changes in life support systems eventually cause death, whereas degenerative changes in reproductive systems eventually cause the cessation of progeny production. Successful reproduction is the ultimate purpose of animal life, and therefore it is important to determine the causes of reproductive aging and the way reproductive aging has been sculpted by natural selection during evolution. Because most aging studies focus on somatic degeneration and lifespan, relatively little is known about the causes of reproductive aging. To identify and characterize factors that influence reproductive aging, we used the nematode worm C. elegans, which is a prominent model for studies of somatic aging. Our results indicate that reproductive aging in worms can be delayed by cold temperature, by restricting nutrient uptake, by diminishing insulin signaling, and by an anticonvulsant medicine that acts on the nervous system. These studies identify genetic pathways and environmental factors that influence reproductive aging. Surprisingly, reproductive aging was not influenced by progeny production early in the reproductive period, indicating that using the germ line to produce progeny does not accelerate degenerative changes. These results suggest that reproductive aging is not caused by use-dependent mechanisms.
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