articleScience AdvancesJan 2, 2026GOLD OA

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

SYShweta YadavXPXingxiu PanSLShengxi LiPLPaige LaRae MartinNHNgoc Hoang

UPMC Health System · University of Pittsburgh Medical Center · +5 more institutions

PubMed
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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 Lb NOX, which converts NADH to NAD + . Lb NOX 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…

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Topics & keywords

Topics
Keywords
  • NAD+ kinase
  • Redox
  • Oxidative stress
  • Metabolism
  • Nicotinamide adenine dinucleotide
  • Enzyme
  • Transgene
  • Mutant
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