Gabrawy, Mariann M.Westbrook, ReyhanKing, AustinKhosravian, NickOchaney, NeerajDeCarvalho, TagideWang, QinchuanYu, YuqiongHuang, QiaoSaid, AdamAbadir, MichaelZhang, CissyKhare, PratikFairman, Jennifer E.Le, AnneMilne, Ginger L.Vonhoff, Fernando JWalston, Jeremy D.Abadir, Peter M.2024-04-022024-04-022024-03-13Gabrawy, Mariann M., Reyhan Westbrook, Austin King, Nick Khosravian, Neeraj Ochaney, Tagide DeCarvalho, Qinchuan Wang, et al. “Dual Treatment with Kynurenine Pathway Inhibitors and NAD+ Precursors Synergistically Extends Life Span in Drosophila.” Aging Cell n/a, no. n/a (n.d.): e14102. https://doi.org/10.1111/acel.14102.https://doi.org/10.1111/acel.14102http://hdl.handle.net/11603/32792Tryptophan 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.18 pagesen-USCreative Commons Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/agingkyneurninelongevity regulationNADtryptophanText