Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome.

Autor: Sember E; Department of Biology, University of Louisville, Louisville, KY 40292, USA., Chennakesavula R; Department of Biology, University of Louisville, Louisville, KY 40292, USA., Beard B; Department of Biology, University of Louisville, Louisville, KY 40292, USA., Opoola M; Department of Biology, University of Louisville, Louisville, KY 40292, USA., Hwangbo DS; Department of Biology, University of Louisville, Louisville, KY 40292, USA.
Jazyk: angličtina
Zdroj: G3 (Bethesda, Md.) [G3 (Bethesda)] 2024 May 07; Vol. 14 (5).
DOI: 10.1093/g3journal/jkae056
Abstrakt: Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in the WRN gene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS. In this study, using the null mutant flies (WRNexoΔ) for the gene WRNexo (CG7670), homologous to the exonuclease domain of WRN in humans, we examined how diets affect the lifespan, stress resistance, and sleep/wake patterns of a Drosophila model of WS. We observed that dietary restriction (DR), one of the most robust nongenetic interventions to extend lifespan in animal models, failed to extend the lifespan of WRNexoΔ mutant flies and even had a detrimental effect in females. Interestingly, the mean lifespan of WRNexoΔ mutant flies was not reduced on a protein-rich diet compared to that of wild-type (WT) flies. Compared to WT control flies, the mutant flies also exhibited altered responses to DR in their resistance to starvation and oxidative stress, as well as changes in sleep/wake patterns. These findings show that the WRN protein is necessary for mediating the effects of DR and suggest that the exonuclease domain of WRN plays an important role in metabolism in addition to its primary role in DNA-repair and genome stability.
Competing Interests: Conflicts of interest The authors declare no conflict of interest.
(© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje