Association between whole-blood NAD+ concentration and frailty in community-dwelling older adults: the Itabashi Longitudinal Study on Aging
In 529 community-dwelling Japanese adults aged 65 and over, the 32 participants (6.0%) meeting revised J-CHS frailty criteria had lower median whole-blood NAD+ concentration than non-frail participants. Multivariable models adjusted for age, sex and fasting time, with restricted cubic spline, Firth penalised-likelihood and haematological sensitivity analyses. This is one of the few sizeable human datasets linking circulating NAD+ to a functional phenotype, but it is cross-sectional with a small frail subgroup and must be read alongside evidence that whole-blood NAD+ does not track chronological age.
Evidence
4/10
Emerging Evidence
Sample
529
subjects
Duration
Single cross-sectional wave (2025)
study period
Journal
GeroScience
Sep 2026
Full Abstract
NAD+ is central to energy metabolism, redox reactions and cellular signaling, but human evidence linking circulating NAD+ concentrations to frailty remains limited. This cross-sectional analysis included community-dwelling adults aged 65 years and over from the 2025 wave of the Itabashi Longitudinal Study on Aging. Frailty was assessed using the revised Japanese Cardiovascular Health Study criteria. Among 529 participants (54.3% women), 32 (6.0%) had frailty, and median whole-blood NAD+ concentration was lower among participants with frailty than among those without.
Key Findings
- 01
529 community-dwelling adults aged 65+ (54.3% women) from the 2025 ILSA wave
- 02
32 participants (6.0%) met revised Japanese Cardiovascular Health Study frailty criteria
- 03
Median whole-blood NAD+ concentration was lower in the frail group
- 04
Association persisted in multivariable models adjusted for age, sex and fasting time
- 05
Restricted cubic spline, Firth penalised-likelihood and haematological sensitivity analyses supported the association
Structured Methods
- Study Design
- Observational cross-sectional cohort
- Sample Size
- 529 subjects
- Study Duration
- Single cross-sectional wave (2025)
- Methodology
- Cross-sectional analysis of the 2025 wave of the Itabashi Longitudinal Study on Aging. Whole-blood NAD+ quantified and related to frailty status by multivariable linear and logistic regression adjusted for age, sex and fasting time, with restricted cubic spline modelling, Firth penalised-likelihood logistic regression and haematological sensitivity analyses.
- Limitations
- Cross-sectional design - cannot establish direction of causation, and frailty itself may lower NAD+ through reduced activity, nutrition or comorbidity. Only 32 frail participants, so estimates are imprecise. Single Japanese cohort, limiting generalisability. Provides no evidence that raising NAD+ by supplementation reduces frailty risk.
Citations & References
Itabashi Longitudinal Study on Aging investigators (2026). Association between whole-blood NAD+ concentration and frailty in community-dwelling older adults: the Itabashi Longitudinal Study on Aging. GeroScience. https://doi.org/10.1007/s11357-026-02545-9
Sample member
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