Association of Human Whole Blood NAD + Contents With Aging.
Level 4 - case-series / case-control
Cross-sectional observational study
PubMed 35388296 · doi:10.3389/fendo.2022.829658
What was done
A cross-sectional study evaluated 1,518 adults (mean age 43.0 years, 52.6% men) free of cardiovascular disease and cancer from the Jidong community between 2019 and 2020. Whole blood NAD+ concentrations were measured using cycling assays and liquid chromatography-mass spectrometry. Participants were stratified into five chronological age groups (≤29, 30–39, 40–49, 50–59, and ≥60 years). General linear regression models and sex-interaction analyses were used to assess the relationship between age and whole blood NAD+ levels.
What was found
Mean whole blood NAD+ across all participants was 33.0 ± 5.5 μmol/L, with higher levels in men than in women (34.5 vs. 31.3 μmol/L). In the overall cohort, NAD+ declined with age before 50 years, reaching significance in the 40–49 year group (β = -1.12; 95% CI, -2.18 to -0.06), but this trend disappeared after age 50. Sex significantly modified this relationship (p for interaction = 0.003). In men, NAD+ decreased with age compared to the ≤29 group, reaching significance in the ≥60 age group (adjusted β = -2.16; 95% CI, -4.16 to -0.15). In women, whole blood NAD+ did not significantly differ among the five age groups. Significant differences were also noted for meat diet across NAD+ quartiles (p = 0.01).
Why it matters
This study provides large-scale human whole blood NAD+ baseline data across adult age groups and indicates that age-related blood NAD+ depletion may be sex-specific, predominantly occurring in middle-aged and older men.
Limits
The cross-sectional design cannot determine longitudinal decline within individuals or establish causality. The study was conducted in a single Chinese community and excluded individuals with cancer or cardiovascular disease, limiting generalizability. Whole blood measurements primarily reflect blood cells rather than tissue-specific NAD+ concentrations in organs such as liver, muscle, or brain.