The Connection Between Aging and a Reduced Level of NAD+ in the Body
The human body is made of 30-40 trillion cells, and all of them rely on a coenzyme called nicotinamide adenine dinucleotide (NAD+) to work properly and carry out their day-to-day functions.1 This makes NAD+ a fundamental determinant of health and wellness – or lack thereof.
Research shows that NAD+ levels decline with age. This decline plays a crucial role in the development of age-related conditions such as diabetes, Alzheimer's disease, obesity, heart disease, and loss of muscle tone.1-3
Scientists around the world are exploring how boosting NAD+ levels in the body can improve aging by delaying the onset of disease and disability to live a healthier, higher quality life.
What is NAD+ and What Does it Do in the Body?
Scientists have known about nicotinamide adenine dinucleotide for at least 100 years. As a coenzyme, or “helper” molecule, NAD+ binds to other enzymes to help enable reactions on a cellular level. Although a helper molecule might not sound important, NAD+ is vital to countless bodily functions; without it, the human body couldn't work properly and living wouldn’t be possible.1
NAD+ has two general and fundamental roles in the human body:
- Creation of energy. NAD+ is key to cellular metabolism and helps turn food into the energy the body needs to function.1,2
- Regulation of cellular processes. As a helper molecule, NAD+ directly and indirectly influences numerous cellular functions, including DNA repair, gene expression, and immune function.1,2,4
How NAD+ Affects Aging
NAD+ declines with age, the primary reason for which is twofold. First, as the body ages, it produces less NAD+. Second, damage from inflammation, oxidative stress, and malfunctioning DNA depletes NAD+ from the body. As a result, numerous biological processes that are dependent on NAD+ are altered.1-3
Low NAD+ is a central aspect of many age-related problems. The reduction in NAD+ results in a decline in healthy cellular metabolism. This, in turn, results in the familiar signs of aging – loss of muscle tone, reduction in exercise capacity, obesity, frailty, etc. The decline in NAD+ is also linked with many age-related diseases.1-4
Since NAD+ is fundamental to cellular operation, there aren't many bodily functions it doesn’t affect. Research is exploring the connection between declining NAD+ and the hallmarks of cellular aging. These hallmarks are considered the underlying core of how the body ages.
The cellular hallmarks of aging are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis (protein stability), deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.2,5,6,
Don't worry – you don't have to understand what they mean – and this article isn't going to subject you to lengthy explanations. Here's what we know about the influence of NAD+ on several of the hallmarks and how boosting NAD+ levels in the body might offset and improve the effects of aging.
1. Genomic Instability
Genomic instability means there are defects in the processes that control the way a cell divides. As a result, the genome is altered during cell division and doesn't make an exact copy of the original pattern. When DNA doesn't replicate correctly or repair damage, it causes mutations in the genetic code.5,6
A decline in NAD+ inhibits the cell's ability to divide and facilitate DNA repair. Research shows that replenishing NAD+ in aged mice increased the cell’s capacity to repair damaged DNA.2,7
2. Telomere Attrition
At the end of every chromosome is a protective cap called a telomere. Each time a cell divides, telomeres become shorter. When telomeres get too short, cells can no longer reproduce, which causes tissues to degenerate and eventually die.5,6 Shortened telomeres are linked to many chronic conditions associated with age.8
Telomere length and function are protected by a family of proteins called sirtuins. Among their many functions, sirtuins regulate and delay cellular aging – and they are dependent on NAD+ to function properly.3,9,10 A recent study on mice showed that boosting NAD+ is associated with an increase in sirtuin activity. Increasing sirtuin activity stabilizes telomeres, reduces DNA damage, and improves telomere-dependent conditions.11
3. Cellular Senescence
Another biological process of aging is called cellular senescence. Senescence literally means "the process of growing old." When aging and damaged cells die, your immune system normally clears them from your body. 5,6 Senescent cells, on the other hand, are malfunctioning cells that have stopped dividing but don’t die and remain in the body. They accumulate with age and contribute to adverse conditions associated with aging.12,13
Studies have shown that boosting levels of NAD+ in older mice rejuvenated and prevented senescence of muscle stem cells and increased overall lifespan.14,15
4. How Do You Increase NAD+ in the Body?
Many of the wellness strategies and habits that support a healthy lifestyle increase NAD+ in the body. Getting adequate exercise, intermittent fasting, eating a healthy diet, getting adequate sleep, and avoiding physical stressors like toxins and excess sun exposure can increase NAD+.1,3
If adhering to a healthy lifestyle is difficult due to age or health status, then taking a supplement like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) is the next best option. Both are a form of vitamin B3 (niacin) and are converted by the body into NAD+.
Lab studies show that supplementing with NR or NMN improves multiple physiological functions in mice and other organisms.16-18 One study showed that adding NMN to drinking water improved cardiovascular function in older mice.19 Another study in mice showed that supplementing with NR can support impaired cognitive function associated with aging.20
Most of the studies on how NAD+ impacts aging have been done in the lab and on small mammals. A 12-month study on mice showed that supplementing with NMN was well-tolerated without any ill effects.17 Long-term data on supplementing NMN in humans isn't available yet. At this point, because there isn't enough data to demonstrate absolute safety, it's best to avoid supplementation if you are pregnant or breastfeeding.
Aging is a complicated series of interconnected processes. Boosting NAD+ in the body has emerged as a potential approach to improve age-related conditions and extend the human lifespan. Much research is currently underway to determine if increasing NAD+ will benefit aging humans.
A Note from Thorne
Several Thorne products contain NR to potentially increase NAD+ levels.
- Chini CCS, Tarragó MG, Chini EN. NAD and the aging process: Role in life, death and everything in between. Mol Cell Endocrinol 2017;455:62-74.
- Covarrubias A, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 2021;22(2):119-141.
- Braidy N, Berg J, Clement J, et al. Role of nicotinamide adenine dinucleotide and related precursors as therapeutic targets . . . : rationale, biochemistry, pharmacokinetics, and outcomes. Antioxid Redox Signal 2019;30(2):251-294.
- Amjad S, Nisar S, Bhat AA, et al. Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Metab 2021;49:101195.
- Guerville F, De Souto Barreto P, Ader I, et al. Revisiting the hallmarks of aging to identify markers of biological age. J Prev Alzheimers Dis 2020;7(1):56-64.
- López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell 2013;153(6):1194-217.
- Fang EF, Kassahun H, Croteau DL. NAD+ replenishment improves lifespan and healthspan . . . via mitophagy and DNA repair. Cell Metab 2021;24(4):566-581.
- Shammas MA. Telomeres, lifestyle . . . and aging. Curr Opin Clin Nutr Metab Care. 2011;14(1):28-34.
- Kane AE, Sinclair DA. Sirtuins and NAD+ . . . . Circ Res 2018;123(7):868-885.
- Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis 2016;2:16017.
- Amano H, Chaudhury A, Rodriguez-Aguayo C, et al. Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease. Cell Metab 2019;29(6):1274-1290.e9.
- van Deursen J. The role of senescent cells in ageing. Nature 2014;509(7501):439-446.
- Kirkland J, Tchkonia T. Cellular senescence: A translational perspective. EBioMedicine 2017;21:21-28.
- Gomes AP, Price NL, Ling AJ, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013;155(7):1624-1638.
- Zhang H, Ryu D, Wu Y, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 2016;352(6292):1436-1443.
- Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, . . . Cell Metab 2011;14(4):528-536.
- Mills KF, Yoshida S, Stein LR, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab 2016;24(6):795-806.
- Frederick DW, Loro E, Liu L, et al. Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab 2016;24(2):269-282.
- de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 2016;15(3):522-530.
- Gong B, Pan Y, Vempati P, et al. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression . . .. Neurobiol Aging 2013;34(6):1581-1588.