Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila.
Aging Cell
; 23(4): e14102, 2024 04.
Article
em En
| MEDLINE
| ID: mdl-38481042
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triptofano
/
Cinurenina
Limite:
Animals
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos