Journal
PLOS ONE
Volume 12, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0176371
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Funding
- Israeli Academy of Sciences
- I-Core
- Binational US-Israel Science Foundation
- Israel Cancer Association
- Koret Foundation
- Israel Cancer Research Fund
- Israel Ministry of Health
- Lir'ot association
- TEVA NNE program
- EFSD
- D- Cure
- ERC: European Research Council
- Yedidut Research Fund
- European Foundation for the Study of Diabetes [MSD 2014_1] Funding Source: researchfish
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The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging phenotype and metabolic defects, and die before four weeks of age. Thus, the effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6 (-/-)mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed background, at 200 days of age, more than 80% of the female knock-out mice were alive whereas only 10% of male knock-out mice survived. In comparison to their wild-type littermates, SIRT6 deficient mice have reduced body weight, increased glucose uptake and exhibit an age-dependent progressive impairment of retinal function accompanied by thinning of retinal layers. Together, these results demonstrate a role for SIRT6 in metabolism and age-related ocular changes in adult mice and suggest a gender specific regulation of lifespan by SIRT6.
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