A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

By D. Friedman, T. Johnson. Genetics, 2002

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age-1(hx546) is a recessive mutant allele in Caenorhabditis elegans that results in an increase in mean life span averaging 40% and in maximal life span averaging 60% at 20 degrees; at 25 degrees age-1(hx546) averages a 65% increase in mean life span (25.3 days vs. 15.0 days) and a 110% increase in maximum life span (46.2 days vs. 22.0 days for wild-type hermaphrodites). Mutant males also show extended life spans. age-1(hx546) is associated with a 75% decrease in hermaphrodite self-fertility as compared to the age-1+ allele at 20 degrees. Using two novel strategies for following the segregation of age-1, we present evidence that longer life results from a mutation in a single gene that increases the probability of survival at all chronological ages. The long-life and reduced-fertility phenotypes cosegregate and are tightly linked to fer-15, a locus on linkage group II. age-1(hx546) does not affect the timing of larval molts, the length of embryogenesis, food uptake, movement, or behavior in any way tested. Although age-1(hx546) lowers hermaphrodite self-fertility, it does not markedly affect the length of the reproductive period with all the increase in life expectancy due to an increase in the length of postreproductive life. In so far as we are aware, this mutant in age-1 is the only instance of a well-characterized genetic locus in which the mutant form results in lengthened fife. It is likely that the action of age-1 in lengthening life results not from eliminating a programmed aging function but rather from reduced hermaphrodite self-fertility or from some other unknown metabolic or physiologic alteration.

Subfields: Aging, Physiology, Safety, Risk, Reliability and Quality

View Paper: https://www.semanticscholar.org/paper/4a0c84cfab2e6351313f154f40238bec7996e572

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Citations in the corpus

Life and death: metabolic rate, membrane composition, and life span of animals. (2007, neutral): “elegans (103, 172), Drosophila (62, 350), and mice (30, 149).”
The plasticity of aging: insights from long-lived mutants. (2005, background): “The DAF-2 receptor activates a conserved PI-3 kinase signaling pathway (Friedman and Johnson, 1988; Hertweck et al., 2004; Morris et al., 1996; Ogg and Ruvkun, 1998; Paradis et al., 1999; Paradis and Ruvkun, 1998; Wolkow et al., 2002) that affects life span, at least in part, by regulating the nucle”
Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans (2002, background): “age-1(hx546) animals live 60–100% longer than wild typ”
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism (2006, background): “elegans p110 was originally identified as age-1 , which is a gene involved in the regulation of development and lifespa”
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity (2003, background): “The positive control age-1 RNAi extended lifespan by 30%, compared with an age-1 mutant that extended lifespan by 100”
Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. (2008, neutral): “…both life-span and stress resistance can be increased by the alteration of several processes, including insulin/IGF-1- like signaling (IIS) (Friedman and Johnson, 1988; Gottlieb and Ruvkun, 1994; Kenyon et al., 1993; Larsen, 1993), caloric intake (Houthoofd et al., 2002), mitochondrial…”
A Transparent Window into Biology: A Primer on Caenorhabditis elegans (2015, neutral): “Recent advances in efficient genome-editing methods (TALEN and CRISPR/ Cas9) in C. elegans now allow investigators to create targeted mutations in nearly any location in the genome in any genetic background (Frøkjær-Jensen 2013; Waaijers and Boxem 2014).”
A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. (2006, methodology): “RNAi Plasmid Design Mammalian RNAi constructs were designed as described (Gaudilliere et al., 2002).”