Academic journal article Genetics

Identification of Mutations That Delay Somatic or Reproductive Aging of Caenorhabditis Elegans

Academic journal article Genetics

Identification of Mutations That Delay Somatic or Reproductive Aging of Caenorhabditis Elegans

Article excerpt

ABSTRACT Aging is an important feature of animal biology characterized by progressive, degenerative changes in somatic and reproductive tissues. The rate of age-related degeneration is genetically controlled, since genes that influence lifespan have been identified. However, little is known about genes that affect reproductive aging or aging of specific somatic tissues. To identify genes that are important for controlling these degenerative changes, we used chemical mutagenesis to perform forward genetic screens in Caenorhabditis elegans. By conducting a screen focused on somatic aging, we identified mutant hermaphrodites that displayed extended periods of pharyngeal pumping, body movement, or survival. One of these mutations is a novel allele of the age-1 gene. age-1 encodes a phosphatidylinositol-3-kinase (PI3K) that functions in the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway. age-1(am88) creates a missense change in the conserved PIK domain and causes dramatic extensions of the pharyngeal pumping and body movement spans, as well as a twofold extension of the lifespan. By conducting screens focused on reproductive aging in mated hermaphrodites, we identified mutants that displayed increased progeny production late in life. To characterize these mutations, we developed quantitative measurements of age-related morphological changes in the gonad. The am117 mutation delayed age-related declines in progeny production and morphological changes in the gonad. These studies provide new insights into the genetic regulation of age-related degenerative changes in somatic and reproductive tissues.

AGING is an important aspect of animal biology. As adult animals advance in chronological age, they display progressive degenerative changes that compromise the function of a wide range of organ systems. These changes affect neuromuscular activities associated with perception and motility, reproductive organs that mediate progeny production, and many other systems. Age-related degenerative changes in life support systems ultimately result in death. Human aging has enormous medical significance, since age-related degenerative changes contribute to functional impairments and mortality in elderly people (Vijg and Campisi 2008). In human females, reproductive aging is an important medical issue because the age-related decline in oocyte quality results in increased birth defects and decreased fertility that culminates in reproductive cessation at menopause (Hartge 2009).

The soil nematode Caenorhabditis elegans has emerged as an important model organism for studies of aging (Guarente and Kenyon 2000; Braeckman et al. 2001; Gershon and Gershon 2002; Olsen et al. 2006). C. elegans has a relatively short adult lifespan of ~2 weeks, and a number of agerelated degenerative changes have been characterized (Collins et al. 2007; Pincus and Slack 2010). Sophisticated genetic techniques have contributed to the identification of a large number of genes that modulate lifespan, and these studies have made important contributions to understanding the genetic control of longevity (Kenyon 2005). These studies have demonstrated that insulin/IGF-1 signaling, mitochondrial function, chemosensory function, dietary intake, and the sir-2 gene are important modulators of adult lifespan.

Many studies of C. elegans aging use lifespan as the primary measurement of aging. Because aging is characterized by widespread degenerative changes, including changes in the reproductive system that may not affect longevity, genes that are important for aging in specific organ systems may not have been identified using lifespan as an assay. To characterize the genetic control of age-related degenerative changes, we have focused on the somatic and reproductive tissues of C. elegans (Huang et al. 2004; Hughes et al. 2007). Two somatic tissues are well suited to analyzing age-related degeneration. The pharynx is the feeding organ of the animal, and the rhythmic contractions of this organ can be easily visualized and display progressive age-related declines (Croll et al. …

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