Separation of reproductive decline from lifespan extension during methionine restriction.

Autor: Wei F; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA., Liu S; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA., Liu J; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA., Sun Y; Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA., Allen AE; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA., Reid MA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA., Locasale JW; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. dr.jason.locasale@gmail.com.; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA. dr.jason.locasale@gmail.com.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2024 Aug; Vol. 4 (8), pp. 1089-1101. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1038/s43587-024-00674-4
Abstrakt: Lifespan-extending interventions are generally thought to result in reduced fecundity. The generality of this principle and how it may extend to nutrition and metabolism is not understood. We considered dietary methionine restriction (MR), a lifespan-extending intervention linked to Mediterranean and plant-based diets. Using a chemically defined diet that we developed for Drosophila melanogaster, we surveyed the nutritional landscape in the background of MR and found that folic acid, a vitamin linked to one-carbon metabolism, notably was the lone nutrient that restored reproductive capacity while maintaining lifespan extension. In vivo isotope tracing, metabolomics and flux analysis identified the tricarboxylic cycle and redox coupling as major determinants of the MR-folic acid benefits, in part, as they related to sperm function. Together these findings suggest that dietary interventions optimized for longevity may be separable from adverse effects such as reproductive decline.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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