Sirt6 regulates lifespan in Drosophila melanogaster

Author:

Taylor Jackson R.1ORCID,Wood Jason G.1ORCID,Mizerak Evan1,Hinthorn Samuel1ORCID,Liu Julianna1ORCID,Finn Matthew1ORCID,Gordon Sarah1ORCID,Zingas Louis1,Chang Chengyi1,Klein Mark A.2ORCID,Denu John M.2,Gorbunova Vera34,Seluanov Andrei34,Boeke Jef D.567ORCID,Sedivy John M.1,Helfand Stephen L.1

Affiliation:

1. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912

2. Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726

3. Department of Biology, University of Rochester, Rochester, NY 14627

4. Department of Medicine, University of Rochester, Rochester, NY 14627

5. Institute for Systems Genetics, NYU Langone Health, New York, NY 10016

6. Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016

7. Department of Biomedical Engineering, Tandon School of Engineering, Brooklyn, NY 11201

Abstract

Significance Sirt6 is well known for its role in regulating the aging process, particularly for its ability to extend lifespan in mice when overexpressed. However, the underlying molecular mechanisms responsible for lifespan regulation by Sirt6 are not well understood. Here, we characterized dSirt6 in fruit flies ( Drosophila melanogaster ). We found that dSirt6 functions very similarly to mammalian Sirt6 at the molecular and biochemical levels. Furthermore, overexpressing dSirt6 increased lifespan in flies. dSirt6 overexpression extends lifespan, in part, by opposing the activity of Myc, a master regulator of protein synthesis, which is associated with decreased protein synthesis. These findings have relevance for the treatment of age-related disease by modulating Sirt6 activity.

Funder

HHS | NIH | National Institute on Aging

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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