NAD+ and Aging: Understanding the Research
Takeaway: what the evidence shows
NAD+ is a cellular coenzyme, and age-related findings about it are tissue- and method-dependent. They do not support one universal decline for every person, and they do not establish that increasing NAD+ improves health for everyone.
NAD+ metabolism changes with age, but the size and meaning of any change depend on the tissue studied, the measurement method, and the study population. Findings from animal models, human samples, and different tissues should not be treated as interchangeable. The research therefore supports a careful discussion of age-related NAD+ biology rather than one universal percentage for every person or tissue.
The mechanisms discussed in the research
Reviews of NAD+ biology discuss several contributors to changes in NAD+ availability. Their relative importance can differ by tissue, age, model, and study design, so these mechanisms provide context for interpreting research rather than a clinical explanation for an individual.
The first contributor: NAD+ consumption
One area discussed is NAD+ consumption. NAD+ is a substrate for PARPs — poly(ADP-ribose) polymerases — enzymes involved in cellular responses to DNA damage. This provides one possible route by which cellular demand for NAD+ can change, but the size and importance of that effect depend on biological context and the evidence available for a particular tissue or model.
The second contributor: NAD+ biosynthesis
Another area is NAD+ biosynthesis. NAD+ can be produced through pathways involving tryptophan, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), with NAMPT discussed as a key enzyme in the salvage pathway. How these pathways vary with age, and how that variation differs across tissues and studies, remains an evidence question rather than a basis for personal treatment advice.
The third contributor: CD38 and NAD+ consumption
CD38 is another enzyme discussed in relation to NAD+ consumption. Research has examined whether changes in CD38 activity or expression contribute to age-related NAD+ differences, but the magnitude and relevance of that contribution can vary by tissue, model, and study. Terms such as an “NAD+ leak” should therefore be read as a research description, not a diagnosis.
What this means for interpreting interventions
These mechanisms help explain why researchers study NAD+ precursors and enzymes involved in NAD+ metabolism. They do not establish that a supplement, inhibitor, or combination is effective or appropriate for an individual. Animal, cellular, and human studies answer different questions, and interpretation requires attention to tissue measurements, study design, safety, and demonstrated clinical outcomes.
A strategy aimed at one pathway cannot automatically be judged less effective than a strategy aimed at several. Comparative human evidence would be needed before making that claim, and a mechanistic rationale should not be presented as a personal protocol or medical recommendation.
This essay is adapted from Chapter 3 of NAD+ vs MOTS-c: The Honest Comparison. Read more about the book →
Related reading: MOTS-c and Exercise: Understanding the Research →
References
Covarrubias et al., NAD+ metabolism and its roles in cellular processes during ageing. Read the PubMed record →
This article is for educational purposes and is not medical advice.
For a side-by-side explanation of the molecules and their evidence, read NAD+ vs MOTS-c: What’s the Difference?.