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Ageing

A midlife crisis for sirtuins

Nature Reviews Molecular Cell Biology volume 12, page 688 (2011)Cite this article

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Guarente and colleagues originally found in 1999 that increased expression of the protein silent information regulator 2 (Sir2) extended lifespan in budding yeast. They subsequently reported in Nature in 2001 that extra copies of the Sir2-related gene from Caenorhabditis elegans (sir-2.1) extended worm lifespan by up to 50%. Two approaches led to this conclusion. First, the authors obtained C. elegans strains with duplications of several different chromosomal regions and found that a duplication of chromosome IV that contained sir-2.1 extended worm lifespan, whereas a very similar duplication that lacked the region carrying the sir-2.1 locus did not. This suggested that sir-2.1 was responsible for the phenotype observed. In a second approach, the authors injected worms with a genomic fragment containing sir-2.1 to derive stable transgenic lines, and found that each line which had several extra copies of sir-2.1 showed a long lifespan. This work laid important foundations for other studies of sirtuins in ageing, although mixed reports of their roles have been the cause of some debate in the field.

sirtuins might primarily affect physiological homeostasis and stress responses

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References

ORIGINAL RESEARCH PAPERS

  1. Tissenbaum, H. A. & Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–230 (2001)

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  2. Burnett, C. et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482–485 (2011)

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  3. Viswanathan, M. & Guarente, L. Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature 477, E1–E2 (2011)

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FURTHER READING

  1. Lombard, D. B. et al. Ageing: longevity hits a roadblock. Nature 477, 410–411 (2011)

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Authors
  1. Kim Baumann
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Baumann, K. A midlife crisis for sirtuins. Nat Rev Mol Cell Biol 12, 688 (2011). https://doi.org/10.1038/nrm3218

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