NAD+ and aging: why do NAD+ levels decline as we get older?
Have you ever felt like your body doesn't have the same energy it used to? That your recovery takes longer, you're less sharp, or you simply find it harder to maintain the same level of performance?
Although aging is a complex process, scientific studies point to an important factor that may play a role: a decline in NAD+.
What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in virtually every cell of the body. It plays a central role in hundreds of biological processes.
NAD+ is involved in, among other things:
- The conversion of food into energy
- Mitochondrial function (the powerhouses of the cell)
- DNA repair processes
- Sirtuin activity
- Various metabolic processes
Mitochondrial function is central to cellular energy metabolism. Without sufficient NAD+, cells can carry out their functions less efficiently.
In addition, researchers pay a great deal of attention to the relationship between NAD+ and sirtuins, a group of proteins involved in cellular health and stress response.
Do NAD+ levels actually decline with age?
Scientific research suggests so.
Multiple studies show that NAD+-related metabolites decrease during the aging process. These changes fit within broader biological processes described in the 12 hallmarks of aging.
One of the first studies to investigate this in humans was published by Massudi et al. (2012). The researchers analyzed changes in NAD+ metabolism across different age groups and concluded that aging is accompanied by changes in NAD+-related compounds.
Although the exact decline varies between tissues, individuals, and measurement methods, multiple studies support the idea that NAD+ availability decreases as we age.
What happens when NAD+ declines?
Researchers suspect that lower availability of NAD+ may contribute to changes in various cellular processes.
Cellular energy production
Mitochondria use NAD+ to convert nutrients into usable energy. When NAD+ levels fall, the efficiency of these processes can decrease.
Because virtually every cell depends on energy, a decline in NAD+ can have consequences for overall cellular function.
Mitochondrial function
Mitochondria are often described as the cell’s powerhouses. Various studies suggest that a decline in NAD+ is associated with changes in mitochondrial performance during aging.
Mitochondrial health is now seen as an important part of research into longevity and healthy aging.
DNA repair
Small amounts of damage occur to our DNA every day. The body has various DNA repair mechanisms that depend on sufficient NAD+.
When more DNA damage needs to be repaired, more NAD+ may also be consumed.
Sirtuin activity
Sirtuins are enzymes involved in various processes related to cellular health. Their function depends on NAD+.
When NAD+ levels decline, this may affect the activity of these enzymes.
A key study: Gomes et al. (2013)
One of the most frequently cited studies in this field was published in the scientific journal Cell.
The researchers found that older mice had significantly lower NAD+ levels than young mice. In addition, they saw that restoring NAD+ levels led to improvements in various markers of mitochondrial function.
Although results from animal studies cannot automatically be translated to humans, this study has drawn a lot of attention to the possible role of NAD+ during the aging process.
Many of the well-known statements about age-related declines in NAD+ originate from studies like this.
Why does NAD+ decline during aging?
Scientists think multiple factors play a role in this.
Increased consumption of NAD+
As we get older, certain enzymes that consume NAD+ become more active.
Examples include PARP enzymes, which are involved in DNA repair, and CD38, an enzyme that breaks down NAD+.
More DNA damage
Because DNA repair processes require NAD+, a greater need for repair can lead to higher consumption of NAD+.
Changes in NAD+ production
The efficiency with which the body produces NAD+ can also change during aging.
The decline in NAD+ is likely the result of a combination of these factors.
What do recent review studies say?
Modern review articles confirm that a decline in NAD+ appears to be a recurring hallmark of aging.
A comprehensive review published in Nature Metabolism describes how NAD+ levels in various tissues decline during aging and what consequences this may have for cellular function.
More and more researchers consider a decline in NAD+ to be one of the mechanisms that may contribute to age-related changes in energy production, repair processes, and mitochondrial function.
The role of NMN
Because NAD+ itself is poorly absorbed, much research focuses on NAD+ precursors.
One of the best-known precursors is NMN (nicotinamide mononucleotide).
NMN is used by the body as a building block for the production of NAD+. As a result, NMN has been a major focus in research on healthy ageing in recent years.
Although much more research is needed to fully understand all effects, several human studies show that NMN can increase NAD+ levels in adults.
For example, a recent human NMN study showed that Uthever® NMN increased serum NAD+/NADH by 38% after 60 days.
In addition, a lot of research is being done into various NAD+ precursors, including NMN and nicotinamide riboside (NR).
For people exploring healthy ageing, NMN is therefore among the most studied compounds within the NAD+ domain.
Conclusion
NAD+ plays an essential role in energy production, mitochondrial function, DNA repair, and various other processes in the body.
Scientific research suggests that NAD+ levels decline during the ageing process, and that this decline may affect how our cells function.
Although ageing can never be completely stopped, scientific interest is growing in strategies aimed at supporting healthy NAD+ levels. NMN is one of the most studied NAD+ precursors within the broader field of longevity.
Sources
Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ.
Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
DOI: https://doi.org/10.1371/journal.pone.0042357
Gomes AP, Price NL, Ling AJY, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA.
Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging.
DOI: https://doi.org/10.1016/j.cell.2013.11.037
Covarrubias AJ, Perrone R, Grozio A, Verdin E.
NAD+ metabolism and its roles in cellular processes during ageing.
DOI: https://doi.org/10.1038/s41580-020-00313-x
