Research

Energy balance

Aging in human tissue is associated with a significant decline in NAD+ levels, driven by PARP hyperactivation due to accumulated oxidative DNA damage, which subsequently reduces SIRT1 activity and energy production.

This research highlights that NAD+ levels naturally decline with age in humans, partly due to DNA repair demands (PARP activity). While this paper does not prescribe a specific intervention, it supports the theoretical basis for NAD+ boosting strategies (like NMN or NR supplementation) aimed at mitigating age-related metabolic decline. Focus on managing oxidative stress through diet and lifestyle to potentially spare NAD+ stores.

GoodSupportsHIGH confidence
This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD+ catabolism in human tissue. The resulting NAD+ depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling.
Hassina Massudi et al. · PLoS ONE · 2012

Why this rating

The study uses human tissue samples (n=49) with rigorous biochemical assays, though it is observational/cross-sectional rather than interventional.

Source

Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue

Hassina Massudi et al. · PLoS ONE · 2012

DOI 10.1371/journal.pone.0042357

cross_sectional · n=49Cited 544×
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DOI resolved against Crossref · corpus check 2026-06-10

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