A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span

Abstract

C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span.

CCAR‐1 is a negative regulator of the heat‐shock response in Caenorhabditis elegans

“…The following C. elegans strains were used in this study: Bristol N2 (wild‐type), sir‐2.1Δ (LG339) (Viswanathan & Tissenbaum, 2013; Viswanathan, Kim, Berdichevsky, & Guarente, 2005), sir‐2.3Δ (RB654) (Barstead & Moerman, 2006), Q35::YFP (AM140) (38), HSF‐1::GFP (EQ73) (Chiang et al, 2012), and the pC12C8.1::GFP reporter strain (39). All strains were grown at 23°C and maintained on standard nematode growth media (NGM) containing the Escherichia coli strain OP50.…”

Autophagy and ageing: Insights from invertebrate model organisms

“…In higher eukaryotes, sirtuins have been implicated in ageing although their effect on lifespan remains controversial. Overexpression of sir-2.1 in C. elegans and dSir2 in Drosophila has been reported to extend lifespan (Tissenbaum and Guarente, 2001;Viswanathan et al, 2005;Rogina and Helfand, 2004). However, recent studies suggest that increased longevity observed in strains overexpressing sirtuin genes was due to unrelated mutations lurking in the genome and not to sirtuin overexpression per se.…”

Antioxidants reveal an inverted U‐shaped dose‐response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans

“…The effect of RSV on lifespan per se has also been widely tested and positive effects documented in both invertebrates and vertebrates (Bhullar & Hubbard, 2015). In C. elegans , a relatively small but reproducible lifespan‐extending effect has been documented by several groups (Wood et al ., 2004; Viswanathan et al ., 2005; Bass et al ., 2007; Agarwal & Baur, 2011; Morselli et al ., 2010; Zarse et al ., 2010). …”