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A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span.
Dev Cell 2005; 9(5):605-15DC

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.

Authors+Show Affiliations

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16256736

Citation

Viswanathan, Mohan, et al. "A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. Elegans Life Span." Developmental Cell, vol. 9, no. 5, 2005, pp. 605-15.
Viswanathan M, Kim SK, Berdichevsky A, et al. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell. 2005;9(5):605-15.
Viswanathan, M., Kim, S. K., Berdichevsky, A., & Guarente, L. (2005). A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Developmental Cell, 9(5), pp. 605-15.
Viswanathan M, et al. A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. Elegans Life Span. Dev Cell. 2005;9(5):605-15. PubMed PMID: 16256736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. AU - Viswanathan,Mohan, AU - Kim,Stuart K, AU - Berdichevsky,Ala, AU - Guarente,Leonard, PY - 2005/05/17/received PY - 2005/08/24/revised PY - 2005/09/28/accepted PY - 2005/11/1/pubmed PY - 2006/1/18/medline PY - 2005/11/1/entrez SP - 605 EP - 15 JF - Developmental cell JO - Dev. Cell VL - 9 IS - 5 N2 - 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. SN - 1534-5807 UR - https://www.unboundmedicine.com/medline/citation/16256736/A_role_for_SIR_2_1_regulation_of_ER_stress_response_genes_in_determining_C__elegans_life_span_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1534-5807(05)00379-5 DB - PRIME DP - Unbound Medicine ER -