C. elegans as a premier longevity and aging model

and aging model Aging studies in mammals are challenging owing to relatively long life spans and a limited set of genetic tools that are capable of assessing the genome-wide changes associated with disease. By contrast, C. elegans lives for only 2-3 weeks and is easily propagated in culture, facilitating rapid genetic analyses. Genetic resources for C. elegans include hundreds of publicly available mutant strains; full-genome RNA interference (RNAi) libraries, which allow efficient knockdown of gene expression by simply feeding worms with bacteria expressing double-stranded RNAs (dsRNAs); genedeletion strains, which are being generated for each of the ~19,000 genes; and >2000 promoter::gfp strains, which allow characterization of cellular and sub-cellular gene expression patterns. Moreover, all of the 959 lineage-invariant somatic cells of C. elegans are post-mitotic, making the worm an attractive model for aging in non-dividing cells such as mammalian muscle cells and neurons that depend on maintenance instead of cell turnover for their longevity. The mitotically dividing C. elegans germline, which also ages (Garigan et al., 2002), provides an excellent model for the study of age-related reproductive decline (Hughes et al., 2007). Although signals from the germline influence life span (Hsin and Kenyon, 1999), and life span and reproductive span are linked (Luo et al., 2009), postmitotic somatic cell integrity limits the overall life span of the animal (Herndon et al., 2002). Importantly, C. elegans shares many similarities with mammals and humans, including aging and functional senescence (Fig. 1). Aging worms experience a decline in mobility (Herndon et al., 2002; Huang et al., 2004; Hsu et al., 2009), chemotaxis (Murakami and Murakami, 2005) and reproductive capacity (Hughes et al., 2007), and become increasingly susceptible to lethal infections (Garigan et al., 2002; Garsin et al., 2003). Exogenous expression of proteins such as amyloid beta (1-42) [A(1-42)] and poly glutamine (polyQ) also make the worm a model for late-onset diseases such as Alzheimer’s disease and Huntington’s disease (Link, 1995; Faber et al., 1999). These features make C. elegans an excellent system to study conserved aging pathways and age-related diseases in mammals.