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Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila.
- Source :
- Aging Cell; Apr2024, Vol. 23 Issue 4, p1-18, 18p
- Publication Year :
- 2024
-
Abstract
- Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, and in some animals, NAD+. Aging and inflammation are associated with increased levels of kynurenine pathway (KP) metabolites and depleted NAD+, factors which are implicated as contributors to frailty and morbidity. Contrastingly, KP suppression and NAD+ supplementation are associated with increased life span in some animals. Here, we used DGRP_229 Drosophila to elucidate the effects of KP elevation, KP suppression, and NAD+ supplementation on physical performance and survivorship. Flies were chronically fed kynurenines, KP inhibitors, NAD+ precursors, or a combination of KP inhibitors with NAD+ precursors. Flies with elevated kynurenines had reduced climbing speed, endurance, and life span. Treatment with a combination of KP inhibitors and NAD+ precursors preserved physical function and synergistically increased maximum life span. We conclude that KP flux can regulate health span and life span in Drosophila and that targeting KP and NAD+ metabolism can synergistically increase life span. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14749718
- Volume :
- 23
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Aging Cell
- Publication Type :
- Academic Journal
- Accession number :
- 176635916
- Full Text :
- https://doi.org/10.1111/acel.14102