Age-associated changes in oxidative stress and NAD+ metabolism in human tissue
Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ, Sabharwal P
Key finding
Skin NAD+ declines with age in humans, correlating with rising oxidative stress and poly-ADP-ribose accumulation — direct human evidence of the age-related NAD+ deficit.
Summary
One of the earliest and most-cited demonstrations that tissue NAD+ declines with chronological age in humans. Massudi and colleagues analyzed skin biopsy samples from healthy male and female donors spanning a wide age range and quantified NAD+, NADH, and markers of oxidative stress by HPLC and biochemical assays. Total NAD+ content declined significantly with age in both sexes, with concurrent increases in oxidative stress markers (lipid peroxidation, protein carbonyls) and in poly-ADP-ribose accumulation — consistent with PARP hyperactivation consuming NAD+ in response to accumulating DNA damage. The study cohort was modest (n ≈ 30) and tissue-specific (dermal), but it provided the first direct human evidence for the age-associated NAD+ decline that had been documented in rodents. The findings anchored the hypothesis that PARP-driven NAD+ consumption is a causal contributor to the aging phenotype and motivated subsequent CD38- and PARP-inhibitor investigations.
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