Longevity & Aging
aging decreases cellular NAD+
In plain terms: Does NAD+, a key cellular energy molecule, fall with age?
Leans support Longevity & Aging 🔬 Includes disconfirming
Part of: • Aging
RefutedContestedStrong support
consensus score 0.49
Yes, agreed across many labs, though it's an observed link and the human drop varies by tissue.
📅 Last reviewed: 2026-07-14 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Population patterns (Observational)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
6 support 0 contradict 4 tested null 2 mixed · 12 sources, 6 independent groups
What the evidence shows
Tissue/blood NAD+ falls with age across multiple independent labs - one of Sinclair's better-evidenced premises, though the human magnitude is heterogeneous and tissue-specific (more robust in rodents).
The evidence (15)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Migliavacca E, Tay SKH, Patel HP, Sonntag T, Civiletto G, McFarlane C, Forrester T, Barton SJ, Leow MK, Antoun E, Charpagne A, Seng Chong Y, Descombes P, Feng L, Francis-Emmanuel P, Garratt ES, Giner MP, Green CO, Karaz S, Kothandaraman N, Marquis J, Metairon S, Moco S, Nelson G, Ngo S, Pleasants T, Raymond F, Sayer AA, Ming Sim C, Slater-Jefferies J, Syddall HE, Fang Tan P, Titcombe P, Vaz C, Westbury LD, Wong G, Yonghui W, Cooper C, Sheppard A, Godfrey KM, Lillycrop KA, Karnani N, Feige JN 2019 · Nat Commun | observational | mixed | moderate | Muscle NAD+ biosynthesis (NAMPT) and mitochondrial capacity reduced in human sarcopenia across three independent cohorts (n=119) |
| Benjamin C, Crews R 2024 · Nutrients | observational | supports | low | Reviews NMN trials; notes age-related NAD+ decline is real but human magnitude is variable and inconsistently measured |
| Yusri K, Jose S, Vermeulen KS, Tan TCM, Sorrentino V 2025 · npj Metab Health Dis | observational | supports | low | Review synthesizing multi-lab evidence that tissue NAD+ metabolism declines with age and modulates mitochondrial function |
| Zhu XH, Chen W 2018 · Front Aging Neurosci | observational | supports | low | Methods review, no new data. NAD–age evidence is reproduced from prior work: 'Figure 9 shows an application of the NAD assay in healthy subjects, which detected strong age-dependent changes in [NAD+], [NADH], [NAD]total ... and RXNAD'; groups 'young (21–26 year, n = 7), middle (33–36 year, n = 4) and old (59–68 year, n = 6) subjects. Figure adapted from Zhu et al. (2015b).' Review — zero weight; Zhu 2015b (PNAS) is the primary. |
| Katsyuba E, Mottis A, Zietak M, De Franco F, van der Velpen V, Gariani K, Ryu D, Cialabrini L, Matilainen O, Liscio P, Giacchè N, Stokar-Regenscheit N, Legouis D, de Seigneux S, Ivanisevic J, Raffaelli N, Schoonjans K, Pellicciari R, Auwerx J 2018 · Nature | animal | tested-null | moderate | De novo NAD+ synthesis (ACMSD inhibition) raises NAD+ and improves mitochondrial function - supports functional importance of declining NAD+ |
| Chini CCS, Peclat TR, Warner GM, Kashyap S, Espindola-Netto JM, de Oliveira GC, Gomez LS, Hogan KA, Tarragó MG, Puranik AS, Agorrody G, Thompson KL, Dang K, Clarke S, Childs BG, Kanamori KS, Witte MA, Vidal P, Kirkland AL, De Cecco M, Chellappa K, McReynolds MR, Jankowski C, Tchkonia T, Kirkland JL, Sedivy JM, van Deursen JM, Baker DJ, van Schooten W, Rabinowitz JD, Baur JA, Chini EN 2020 · Nat Metab | animal | supports | moderate | CD38 ecto-enzyme rises in aging immune cells and drives age-related NAD+ and NMN decline - mechanism for tissue NAD+ fall |
| Tran T, Pencina KM, Schultz MB, Li Z, Ghattas C, Lau J, Sinclair DA, Montano M 2022 · JAIDS | observational | supports | low | JAIDS 2022 muscle NAD decline driven by HIV/HCV/CMV NOT age; tangential confounded-by-infection |
| Roichman A, Elhanati S, Aon MA, Abramovich I, Di Francesco A, Shahar Y, Avivi MY, Shurgi M, Rubinstein A, Wiesner Y, Shuchami A, Petrover Z, Lebenthal-Loinger I, Yaron O, Lyashkov A, Ubaida-Mohien C, Kanfi Y, Lerrer B, Fernández-Marcos PJ, Serrano M, Gottlieb E, de Cabo R, Cohen HY 2021 · Nat Commun | animal | supports | moderate | SIRT6 over-expression restores NAD+-linked energy homeostasis and extends healthy lifespan in mice - supports declining NAD+ economy with age |
| Cuenoud B, Ipek Ö, Shevlyakova M, Beaumont M, Cunnane SC, Gruetter R, Xin L 2020 · Front Aging Neurosci | observational | tested-null | low | In-vivo 31P-MRS shows brain NAD declines and tracks ATP production in humans - independent human measurement of NAD decline |
| Oblong JE, Bowman A, Rovito HA, Jarrold BB, Sherrill JD, Black MR, Nelson G, Kimball AB, Birch-Machin MA 2020 · Aging Cell | observational | tested-null | low | Aging human skin shows declining mitochondrial/metabolic output; nicotinamide restores integrity - consistent with cutaneous NAD+ decline |
| Bertoldo MJ, Listijono DR, Ho WJ, Riepsamen AH, Goss DM, Richani D, Jin XL, Mahbub S, Campbell JM, Habibalahi A, Loh WN, Youngson NA, Maniam J, Wong ASA, Selesniemi K, Bustamante S, Li C, Zhao Y, Marinova MB, Kim LJ, Lau L, Wu RM, Mikolaizak AS, Araki T, Le Couteur DG, Turner N, Morris MJ, Walters KA, Goldys E, O'Neill C, Gilchrist RB, Sinclair DA, Homer HA, Wu LE 2020 · Cell Rep | animal | supports | moderate | Oocyte NAD+ falls with reproductive aging in mice; NAD+ repletion rescues fertility - tissue-specific age decline |
| de Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, Imai S, Seals DR 2016 · Aging Cell | animal | tested-null | moderate | NMN supplementation reverses age-associated vascular dysfunction in mice, consistent with an age-related NAD+ deficit |
| Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL, Cartwright DM, Oakey L, Burley CV, Jenkinson N, Wilson M, Lucas SJE, Akerman I, Seabright A, Lai YC, Tennant DA, Nightingale P, Wallis GA, Manolopoulos KN, Brenner C, Philp A, Lavery GG 2019 · Cell Rep | RCT | mixed | low | Elhassan 2019 NR RCT raises muscle NAD+ but human age-decline data sparse; indirect |
| Chubanava S, Treebak JT 2023 · Exp Gerontol | mechanism | supports | low | Narrative review despite a results-style title: 'Here, we review the published data on the role of NAD metabolism in exercise'; 'Data from preclinical studies show that aging of various tissues is accompanied by a decrease in the concentration of nicotinamide adenine dinucleotide (NAD)'. Review — zero weight. |
| Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ 2012 · PLoS ONE | observational | supports | moderate | Massudi 2012 direct human tissue NAD+ neg correlated with age + PARP/oxidative link |
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