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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Abstract
In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults. Downregulation of this pathway activates a forkhead transcription factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults. In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2 mediates chromatin silencing through a histone deacetylase activity that depends on NAD (nicotinamide adenine dinucleotide) as a cofactor. We have surveyed the lifespan of C. elegans strains containing duplications of chromosomal regions. Here we report that a duplication containing sir-2.1-the C. elegans gene most homologous to yeast SIR2-confers a lifespan that is extended by up to 50%. Genetic analysis indicates that the sir-2.1 transgene functions upstream of daf-16 in the insulin-like signalling pathway. Our findings suggest that Sir2 proteins may couple longevity to nutrient availability in many eukaryotic organisms.
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“and subsequent reports indicated that enhanced expression of the worm (sir-2.1) and fly (dSir2) orthologs could extend lifespan in both invertebrate model systems (Rogina and Helfand, 2004; Tissenbaum and Guarente, 2001).”
From The Hallmarks of Aging (2013) · cites this paper as Tissenbaum and Guarente, 2001
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Regulation of SIRT1 activity by genotoxic stress
Yuan, J., Luo, K., Liu, T., & Lou, Z. (2012) · Genes & Development · doi:10.1101/gad.188482.112 · Cited by 79
Ha, C. W., & Huh, W.-K. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq895 · Cited by 77
Impacts of transcriptional regulation on aging and senescence
Roy, A. K., Oh, T., Rivera, O., Mubiru, J., Song, C. S., & Chatterjee, B. (2002) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00006-5 · Cited by 72
Regulation of Chemosensory Receptor Expression and Sensory Signaling by the KIN-29 Ser/Thr Kinase
Lanjuin, A., & Sengupta, P. (2002) · Neuron · doi:10.1016/s0896-6273(02)00572-x · Cited by 71
Individual histone deacetylases in Drosophila modulate transcription of distinct genes
Cho, Y., Griswold, A., Campbell, C., & Min, K.-T. (2005) · Genomics · doi:10.1016/j.ygeno.2005.07.007 · Cited by 71
Mechanisms of aging in senescence-accelerated mice
Carter, T. A., Greenhall, J. A., Yoshida, S., Fuchs, S., Helton, R., Swaroop, A., Lockhart, D. J., & Barlow, C. (2005) · Genome Biology · doi:10.1186/gb-2005-6-6-r48 · Cited by 64
Sirtuins at the Service of Healthy Longevity
Watroba, M., & Szukiewicz, D. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.724506 · Cited by 64
SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice
Nakamura, Y., Ogura, M., Ogura, K., Tanaka, D., & Inagaki, N. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.10.009 · Cited by 55
Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations
de Magalhães, J. P. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2004.05.003 · Cited by 54
Jankauskas, S. S., Pevzner, I. B., Andrianova, N. V., Zorova, L. D., Popkov, V. A., Silachev, D. N., Kolosova, N. G., Plotnikov, E. Y., & Zorov, D. B. (2017) · Scientific Reports · doi:10.1038/srep44430 · Cited by 41
Nagarajan, P., Agudelo Garcia, P. A., Iyer, C. C., Popova, L. V., Arnold, W. D., & Parthun, M. R. (2019) · Aging Cell · doi:10.1111/acel.12992 · Cited by 43
“…mitochondria, senescence modulate aging and lifespan (Kaeberlein, McVey, & Guarente, 1999; McDonnell, Peterson, Bomze, & Hirschey, 2015; Mostoslavsky et al., 2006; Rogina & Helfand, 2004; Tissenbaum & Guarente, 2001; Viswanathan & Guarente, 2011; Viswanathan, Kim, Berdichevsky, & Guarente, 2005).”
Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy
Bareja, A., Lee, D. E., & White, J. P. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00183 · Cited by 41
Why Is Longevity Still a Scientific Mystery? Sirtuins—Past, Present and Future
Ziętara, P., Dziewięcka, M., & Augustyniak, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010728 · Cited by 40
Between Scylla and Charybdis: p53 links tumor suppression and aging
Campisi, J. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00006-4 · Cited by 33
Do we age on Sirt1 expression?
Sedding, D., & Haendeler, J. (2007) · Circulation Research · doi:10.1161/01.res.0000269326.37165.3d · Cited by 21
Metadata
- Authors
- Tissenbaum, H. A., & Guarente, L.
- Venue
- Nature
- Published
- 2001-03
- Volume
- 410
- Issue
- 6825
- Pages
- 227-230
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 1,603
- References
- 4
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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