Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

clinical paper · 2003

type:clinical paper

year:2003

citation:Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191-196. DOI: 10.1038/nature01960. PMID: 12939617.

LINK

https://pubmed.ncbi.nlm.nih.gov/12939617/

SUMMARY

The founding paper of the case. Reports the discovery of small-molecule activators of the yeast enzyme Sir2 and its human homolog SIRT1; resveratrol, the most potent, is shown to extend Saccharomyces cerevisiae replicative lifespan by approximately 70% in a Sir2-dependent manner and to stimulate SIRT1-dependent deacetylation of p53 in human cells. PMID and DOI both resolved directly on PubMed and via the DOI resolver; title and full author list, including senior author David A. Sinclair, match. Primary peer-reviewed research paper.

NOTES

This is the paper that started the case: a real, published, peer-reviewed result in yeast that was extrapolated, in Sinclair’s own promotional language and in Sirtris Pharmaceuticals’ subsequent $720 million sale to GlaxoSmithKline, into a human anti-aging therapeutic candidate years before the underlying SIRT1-activation mechanism was shown to be an assay artifact (Pacholec et al. 2010).