Perturbation of NAD(P)H metabolism with the <i>Lb</i>NOX xenotopic tool extends lifespan and mitigates age-related changes.

ABSTRACT: Aging involves widespread metabolic dysregulation, including a decline in total nicotinamide adenine dinucleotide (NAD) levels. While NAD precursor supplementation elevates total NAD levels, it does not reveal tissue-specific effects of an altered NADH [reduced form of NAD⁺ (oxidized NAD)]/NAD⁺ balance. To address this, we generated transgenic Drosophila expressing the genetically encoded xenotopic enzyme LbNOX, which converts NADH to NAD⁺. LbNOX expression modulated both NAD(H) and NADP(H) (reduced form of NAD phosphate) metabolites in a sex-dependent manner and rescued neuronal cell death induced by mutant αB-crystallin-associated reductive stress. We demonstrate that tissue-specific targeting of redox NAD metabolism shows distinct ou

SUBMITTER: Yadav S 

PROVIDER: S-EPMC12758502 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature