One of the most discussed observations in modern ageing research is deceptively simple: levels of NAD+, the coenzyme central to cellular energy, appear to decline as we get older. This pattern shows up in tissues ranging from skin and muscle to liver and brain, and across many species, humans included.
The finding matters precisely because NAD+ is so fundamental. If a molecule that powers energy production and repair becomes less available over time, it is fair to ask whether that decline is connected to some of the changes we associate with ageing, and whether supporting NAD+ levels could help. This article sums up what researchers have found, while being careful to separate established observations from open questions.
What the studies report
Across a range of laboratory studies, measured NAD+ concentrations in older tissues are frequently lower than in younger tissues. Some human studies suggest the decline may be substantial across adulthood, though exact figures vary widely depending on the tissue examined and the measurement method used.
- The decline is observed in multiple tissues, not just one organ system.
- It has been reported in several species, suggesting a conserved biological pattern.
- The magnitude reported differs between studies, partly because measuring NAD+ accurately is technically demanding.
An important caveat
Showing that NAD+ declines with age is not the same as proving that the decline causes ageing. Correlation and causation are distinct, and good science treats them that way.
Why might NAD+ fall over time?
Researchers generally describe the decline as a balance problem: a shift between how quickly NAD+ is made and how quickly it is consumed. Several contributing factors have been proposed.
- Increased consumption: enzymes such as CD38, which use up NAD+, tend to become more active with age and during inflammation.
- Reduced recycling: the efficiency of the salvage pathway that regenerates NAD+ may decline over time.
- Accumulated stress: ongoing DNA repair demand keeps PARP enzymes busy, and they too draw on the NAD+ pool.
In other words, the ageing cell may be spending NAD+ faster while replenishing it more slowly, and that combination gradually lowers the available pool.
Why scientists are so interested
The reason NAD+ decline attracts so much attention is that, unlike many features of ageing, it is potentially modifiable. In animal studies, raising NAD+ availability using precursor molecules such as NMN and NR has been associated with improvements in various measures of metabolic and tissue function. This has driven intense interest in whether similar approaches could support healthy ageing in humans.
Restoring NAD+ has emerged as one of the most promising and most scrutinised strategies in the biology of ageing.
Synthesised from reviews of NAD+ precursor research
What we still do not know
It is important to be measured. Much of the most striking evidence comes from cell and animal studies, which do not always translate directly to people. Human clinical trials of NAD+ precursors are ongoing, and while several have reported that precursors can raise blood NAD+ markers and are generally well tolerated, the long-term effects on health outcomes are still being investigated.
The honest summary is this: the decline of NAD+ with age is a well-supported observation, the biology behind it is increasingly well understood, and the therapeutic potential is genuinely exciting. Even so, this is still an active field, and strong claims deserve a healthy measure of caution.
KEY TAKEAWAYS
- Multiple studies report that NAD+ levels decline with age across many tissues and species.
- The decline likely reflects faster consumption and slower regeneration of NAD+.
- A correlation with ageing is well documented, but causation is not fully established.
- Human trials of NAD+ precursors are ongoing; long-term outcomes are still being studied.
References & further reading
- Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22, 119–141.
- Camacho-Pereira, J., et al. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127–1139.
- Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metabolism, 27(3), 529–547.
This article is educational background on the underlying science and is not connected to the intended use of any NadGo™ product.
