학술논문
Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila.
Document Type
Article
Author
Gabrawy, Mariann M.; Westbrook, Reyhan; King, Austin; Khosravian, Nick; Ochaney, Neeraj; DeCarvalho, Tagide; Wang, Qinchuan; Yu, Yuqiong; Huang, Qiao; Said, Adam; Abadir, Michael; Zhang, Cissy; Khare, Pratik; Fairman, Jennifer E.; Le, Anne; Milne, Ginger L.; Vonhoff, Fernando J.; Walston, Jeremy D.; Abadir, Peter M.
Source
Subject
*LIFE spans
*ANIMAL life spans
*TRYPTOPHAN
*KYNURENINE
*DROSOPHILA
*NAD (Coenzyme)
*PHYSICAL mobility
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Language
ISSN
1474-9718
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]