Can NAD+ boosters extend lifespan?
NAD+ boosters are growing in popularity as anti-aging supplements, but might they even help to extend our lifespan?
In this article, we’ll be taking a deep dive into the scientific evidence on NAD+ supplements, helping you to make the best choices you can about how to live a longer and healthier life.
Aging has long been thought of as an inevitable process, but more recent research indicates that the speed and severity of aging differ a lot between individuals (Hayflick, 2000). The evidence shows that in fact, our choices have a significant influence on how we age.
Scientists now understand that aging is caused by a combination of biological, environmental, and lifestyle factors, including physical activity and nutrition (Shiels et al., 2019).
Crucially, if we know how to target these factors wisely, then healthy aging and a longer lifespan are a realistic possibility for each of us.
Understanding aging at the cellular level
Scientific research over the past few decades has identified “nine hallmarks of aging”, which characterize the biological progression of aging at the cellular level (Lopez-Otin et al., 2013). These nine hallmarks can be summarized into three major causes of aging:
- Decreased stability of genes and proteins in cells (DNA damage, epigenetic alterations, loss of proteostasis, telomere attrition);
- Dysfunctional metabolism and cell division (mitochondrial dysfunction, deregulated nutrient sensing at the cellular level, cellular senescence);
- Impaired cell functioning and renewal (stem cell exhaustion, altered intercellular communication).
One key change at the cellular level that drives aging is the natural decline in NAD+ levels with age (Massudi et al., 2012). NAD+ is a helper molecule (coenzyme) found inside our cells that counteracts the hallmarks of aging by contributing to the stability of our genes, healthy metabolism, and the renewal of bodily tissues.
Remarkably, NAD+ levels have been shown to drop by over a half in those over 50 compared with those aged 30–50. This means that if we want to age well and potentially live longer, we need to think about how to increase our NAD+ levels.
How do I increase my NAD+ levels?
Luckily, studies have shown that NAD+ levels can be safely increased by regularly taking NAD+ boosters (Irie et al., 2020; Yoshino et al., 2021), such as:
- Nicotinamide riboside (NR)
- Nicotinamide mononucleotide (NMN)
- Niacin (NA)
All of these boosters are different forms of “NAD+ precursors”, which are converted into NAD+ by the body. Animal experiments have shown that both NR and NMN prevent the typical decline of NAD+ levels with age (Mills et al., 2016; Zhang et al., 2016).
An alternative method of increasing NAD+ is to deliver it directly into the bloodstream using intravenous (IV) NAD+ injections.
How do NAD+ boosters increase longevity?
How do NAD+ levels affect longevity exactly? It turns out that NAD+ is the “molecular food” for a class of active biological molecules (enzymes) known as sirtuins.
Sirtuins are “universal regulators” of aging and longevity (Houtkooper et al., 2012). They have been shown to control lifespan in a wide range of experimental organisms, from single-celled yeast to mice.
For example, one key study found that mice given NR lived about 5% longer than mice who weren’t given a NAD+ booster (Zhang et al., 2016). In human terms, given the average life expectancy in the USA of around 80 years, this 5% increase in lifespan would equate to living 4 years longer.
Evidence for the effects of NMN or NA supplements on longevity is more limited, although NA has been shown to prolong lifespan in microscopic nematode worms (Schmeisser et al., 2013).
The connection between NAD+ levels and sirtuin activity means that maintaining healthy levels of NAD+ is key to aging well and enjoying a longer lifespan.
What about human longevity?
Although the increase of lifespan in mice given NR supplements suggests that NAD+ boosters could extend life in humans too, clinical studies need to be conducted to show that this really is the case.
Clinical studies are the “gold standard” in developing evidence-based therapies using NAD+ boosters on human participants. Over 30 clinical trials are currently underway to study the effects of NAD+ supplements on aging and aging-related diseases, including diabetes and Alzheimer’s disease (Reiten et al., 2021).
By helping to treat the cellular causes of aging and reducing premature death due to disease, NAD+ booster therapies hold great promise for prolonging lifespan in humans to its maximum natural potential. The question of whether life extension beyond this is possible remains an open and tantalizing topic for future investigation (Hayflick, 2000).
Hayflick, L. (2000). The future of ageing. Nature, 408(6809), 267-269. https://doi.org/10.1038/35041709
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012). Sirtuins as regulators of metabolism and healthspan. Nature Reviews Molecular Cell biology, 13(4), 225-238. https://doi.org/10.1038/nrm3293
Irie, J., Inagaki, E., Fujita, M., Nakaya, H., Mitsuishi, M., Yamaguchi, S., … & Itoh, H. (2020). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal, 67(2), 153-160. https://doi.org/10.1507/endocrj.EJ19-0313
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., & Guillemin, G. J. (2012). Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue. PLOS ONE, 7(7), e42357. https://doi.org/10.1371/journal.pone.0042357
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., … & Imai, S. I. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metabolism, 24(6), 795-806. https://doi.org/10.1016/j.cmet.2016.09.013
Reiten, O. K., Wilvang, M. A., Mitchell, S. J., Hu, Z., & Fang, E. F. (2021). Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing. Mechanisms of Ageing and Development, 111567. https://doi.org/10.1016/j.mad.2021.111567
Schmeisser, K., Mansfeld, J., Kuhlow, D., Weimer, S., Priebe, S., Heiland, I., … & Ristow, M. (2013). Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nature Chemical Biology, 9(11), 693-700. https://doi.org/10.1038/nchembio.1352
Shiels, P. G., Buchanan, S., Selman, C., & Stenvinkel, P. (2019). Allostatic load and ageing: linking the microbiome and nutrition with age-related health. Biochemical Society Transactions, 47(4), 1165-1172. https://doi.org/10.1042/BST20190110
Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., … & Klein, S. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224-1229. https://doi.org/10.1126/science.abe9985
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., … & Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. https://doi.org/10.1126/science.aaf2693