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Publication
Inducible chronic NAD deficiency in mice reveals multi-systemic phenotypical,
metabolic, and transcriptional changes.
Authors Benitez-Rosendo A, Feuz MB, Chini CCS, Warner GM, Ciccio Lopez GL, Souza GH,
Bueser KR, Kashyap S, Colman L, Thompson KL, Mazdeh DZ, Lopez SA, Miller LB,
Zwerdling AE, Wandersee MK, Peclat TR, Peixoto Rabelo S, Kanamori KS, Pereira
FC, Cordeiro HS, Strange JL, Lucredi NC, Palmieri Serrano L, Kaundal R, Doles
JD, Rowsey JL, Farr JN, Khosla S, Meyer RG, Meyer-Ficca ML, Chini EN
Submitted By Submitted Externally on 11/3/2026
Status Published
Journal Nature communications
Year 2026
Date Published 9/23/2026
Volume : Pages 17 : Not Specified
PubMed Reference 42918808
Abstract Nicotinamide adenine dinucleotide (NAD) is a metabolic cofactor regulating
energy metabolism, epigenetics, DNA repair, and signaling. Although NAD declines
with vitamin B3 deficiency, disease, and aging, systemic consequences of chronic
depletion remain unclear. Here, we characterize an in vivo model of inducible
NAD deficiency using acquired niacin dependency (ANDY) mice, in which NAD
synthesis becomes dependent on dietary niacin. On a niacin-free diet, ANDY mice
developed widespread tissue NAD depletion and sex-independent multisystem
abnormalities, including kyphosis, reduced bone, lean, and fat mass, impaired
exercise capacity, fur browning, frailty, cataracts, disrupted energy
homeostasis, and shortened lifespan. NAD depletion was accompanied by tissue
inflammation and cellular senescence. Transcriptomic analyses revealed broad
metabolic remodeling and only partial overlap with chronological aging.
Senolytic treatment partially improved functional decline without restoring NAD.
In contrast, dietary niacin repletion reversed phenotypic, biochemical,
senescence-associated, and transcriptional abnormalities, demonstrating that
recovery of tissue NAD levels restored systemic function.




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