Wu, Lindsay E. and Fiveash, Corrine E. and Bentley, Nicholas L. and Kang, Myung‐Jin and Govindaraju, Hemna and Barbour, Jayne A. and Wilkins, Brendan P. and Hancock, Sarah E. and Madawala, Romanthi and Das, Abhijit and Massudi, Hassina and Li, Catherine and Kim, Lynn‐Jee and Wong, Ashley S. A. and Marinova, Maria B. and Sultani, Ghazal and Das, Abhirup and Youngson, Neil A. and Le Couteur, David G. and Sinclair, David A. and Turner, Nigel (2023) SIRT2 transgenic over‐expression does not impact lifespan in mice. Aging Cell, 22 (12). ISSN 1474-9718
Full text not available from this repository.Abstract
The NAD(+) -dependent deacylase family of sirtuin enzymes have been implicated in biological ageing, late-life health and overall lifespan, though of these members, a role for sirtuin-2 (SIRT2) is less clear. Transgenic overexpression of SIRT2 in the BubR1 hypomorph model of progeria can rescue many aspects of health and increase overall lifespan, due to a specific interaction between SIRT2 and BubR1 that improves the stability of this protein. It is less clear whether SIRT2 is relevant to biological ageing outside of a model where BubR1 is under-expressed. Here, we sought to test whether SIRT2 over-expression would impact the overall health and lifespan of mice on a nonprogeroid, wild-type background. While we previously found that SIRT2 transgenic overexpression prolonged female fertility, here, we did not observe any additional impact on health or lifespan, which was measured in both male and female mice on standard chow diets, and in males challenged with a high-fat diet. At the biochemical level, NMR studies revealed an increase in total levels of a number of metabolites in the brain of SIRT2-Tg animals, pointing to a potential impact in cell composition; however, this did not translate into functional differences. Overall, we conclude that strategies to enhance SIRT2 protein levels may not lead to increased longevity.
Item Type: | Article |
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Subjects: | R Medicine > R Medicine (General) |
Depositing User: | Repository Administrator |
Date Deposited: | 02 May 2024 06:42 |
Last Modified: | 02 May 2024 06:42 |
URI: | http://eprints.victorchang.edu.au/id/eprint/1497 |
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