NAD+
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8 Great Reasons NAD+ is Anti-aging
Our cells use NAD+ to make sirtuin proteins work to regulate biological pathways and protect cells from age-related decline. Sirtuins play a crucial role in maintaining the length of telomeres, which are DNA strand end caps that keep our chromosomes from unraveling. Scientists have linked long telomeres with longevity.(1)
Unfortunately, our NAD+ levels drop as we age. One reason is that a compound called CD-38 destroys NAD+. This is a good thing if done modestly, because CD-38 keeps our NAD+ from getting too high and impinging on important biochemical processes, such as sleep-wake and hunger cycles. But as we get older, CD-38 gets too ambitious and destroys too much NAD+. The balance is upended, resulting in too much CD-38, and not enough NAD+.
#1 NAD+ Helps Lengthen Telomeres
Inside the nucleus of a cell, our genes are arranged along twisted, double-stranded molecules of DNA called chromosomes. At the ends of the chromosomes are stretches of DNA called telomeres, which protect our genetic data, make it possible for cells to divide, and hold some secrets to how we age.
Each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive (senescent) or it dies (apoptosis). This telomere shortening process is associated with aging, cancer, and a higher risk of death.
NAD+ is required for functioning of the sirtuin proteins that help maintain the length of telomeres.
Foods and supplements rich in polyphenols, such as resveratrol and pterostilbene, may activate sirtuins and contribute to extending lifespan, but emerging evidence suggests sirtuins function best when NAD+ is activated.(2)
#2 NAD+ Helps Repair Our DNA
DNA is highly vulnerable to damage, which can include broken DNA strands and gene mutations. As DNA damage accumulates, it contributes to the aging process and can result in specific lifespan-shortening diseases like cancer and weakened immunity.(3)
Our DNA can fight back. When damaged, DNA activates an enzyme known as PARP-1 that carries out DNA repair within cells. To do this, however, PARP-1 relies on NAD+. To carry out its function, PARP-1 consumes enormous amounts of NAD+. As we get older and our NAD+ becomes gradually depleted, the ability of PARP-1 to repair DNA is significantly compromised.(4)(5)
Replenishing NAD+ restores the DNA repair process and prevents cell death under stress.(6)(7) In two different animal models of neurodegenerative disease, increasing cellular NAD+ reduced the severity of the disorder, normalized neuromuscular function, delayed memory loss, and extended lifespan.(8)
#3 NAD+ Tunes Immune Cell Signaling
As we age, our immune cells become inconsistent––some become overactive (which can contribute to autoimmune disease) and others slow down (which increases the risk of infection). This process, called immunosenescence, is intimately related to mitochondrial function and energy balance, both of which depend on NAD+ activity.
Thus, adequate intracellular NAD+ is vital for youthful cellular energy, a critically important factor in fending off immunosenescence and maintaining defenses against infections and autoimmune disease.
#4 NAD+ Regulates the Energy Enzymes that Fuel Us
A universal feature of aging is the loss of cellular energy, which results in diminished ATP levels and inadequate cellular fuel necessary to power your body. ATP (Adenosine Triphosphate) is the main source of energy for most cellular processes. All living things, plants and animals, require a continual supply of energy in order to function. The energy is used for all the processes required to keep us alive.(9)
One cause of this energy loss is a breakdown in the efficiency of the electron transport chain, the main pathway through which we extract energy from food and of which NAD+ is an essential component. Disorders ranging from obesity and diabetes to bone loss have been associated with loss of this vital pathway.(10)(11)
Studies show that restoring electron transport chain function by raising levels of NAD+ is a rapid and efficient means of promoting the essential enzymes involved in energy extraction and sustaining youthful cell function. This helps to reduce physiological decline and provides protection from age-related disease.(12)(13)
#5 NAD+ Helps Stabilize Chromosomes
Our chromosomes are complex structures housing our DNA. Think of it this way: DNA is in genes; genes are on chromosomes.
Access to DNA strands for “reading out” genetic instructions requires biochemical control of those proteins to make sure each gene functions properly, but like any complex molecular structure, chromosomes can become unstable. Eventually, instability triggers errors in how genes are interpreted, which ultimately contribute to harmful changes in cell function and structure. Aging is accelerated in the presence of increased chromosome instability.(14)(15)(16).
The enzymes involved in sustaining stable chromosomal structures require NAD+ in order to function properly. When sufficiently present, NAD+ contributes to longevity in animal models showing that NAD+ contributes to longevity; whereas when enzymes that require NAD+ to function are inactive, chromosome structure suffers and cells replicate abnormally.(17)
#6 NAD+ Promotes Brain Health
NAD+ appears essential for sustaining brain health due to its effect on neurotransmitters; in fact, it meets the criteria for a neurotransmitter itself.(18)(19)
Neurotransmitters are brain chemicals that relay signals between nerve cells, and thereby help regulate body-wide functions such as mood, appetite, and stress.
#7 NAD+ Supports Cellular Energy Production
NAD+ was first discovered as an important part of the process that channels chemical energy from foods to the ATP fuel our cells require. Recent studies have revealed that NAD+ is itself a form of “energy currency” similar to ATP, the complex organic chemical that provides energy to drive many processes in living cells.(20)
NAD+ is also a functional signaling molecule in processes related to energy production, including PARP-1 and sirtuins. When DNA damage occurs, PARP-1 consumes large quantities of NAD+, leading to reduced energy production. In addition, high levels of NAD+ can activate sirtuins, permitting them to carry out their metabolic and stress-protective responses and contributing to longevity.(21)
Supporting efficient energy production and adequate ATP levels requires consistent and abundant NAD+. This is critical because as our cellular energy diminishes, so does our life force.
#8 NAD+ Activates Sirtuins, Regulators of Cellular Aging
Proteins called sirtuins are major regulators of cellular aging because they influence fundamental functions such as DNA repair and inflammatory responses. They also influence whether cells enter a replicative cycle or instead die a programmed death (apoptosis).(26)
Compounds that activate sirtuins are eagerly sought as chemical “fountains of youth.” Familiar supplements like resveratrol, pterbolene and quercetin have been evaluated as promising sirtuin activators. (22) (23)(24)
Sirtuin activation has shown great promise in fighting cardiovascular disease and preserving aging brain function, but these longevity-promoters cannot function without sufficient NAD+.(25)(26)
The bottom line is that NAD+ is needed for sirtuins to function.
Joe Garma has written more than 670 articles on his anti-aging blog, GarmaOnHealth, and is currently writing a book, The Ageproof Method, 12 Biohacks for A Long and Strong Life. Prohealth Longevity readers can get his four-part guide, Transform Your Body and Mind here.
References
- Courtney Sperlazza: Is NAD+ the Anti-aging Miracle Pill? Here’s What the Science Says.
- Shin-ichiro Imai, et al: NAD+ and Sirtuins in Aging and Disease.
- Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071-8.
- Ying W, Garnier P, Swanson RA. NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochem Biophys Res Commun. 2003;308(4):809-13.
- Burkle A, Beneke S, Muiras ML. Poly(ADP-ribosyl)ation and aging. Exp Gerontol. 2004;39(11-12):1599-601.
- Wang S, Xing Z, Vosler PS, et al. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008;39(9):2587-95.
- Pittelli M, Felici R, Pitozzi V, et al. Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol Pharmacol. 2011;80(6):1136-46.
- Fang EF, Kassahun H, Croteau DL, et al. NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab. 2016;24(4):566-81.
- Paul May, Bristol University: Adenosine Triphosphate (ATP).
- Ritov VB, Menshikova EV, Azuma K, et al. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab. 2010;298(1):E49-58.
- Shum LC, White NS, Nadtochiy SM, et al. Cyclophilin D Knock-Out Mice Show Enhanced Resistance to Osteoporosis and to Metabolic Changes Observed in Aging Bone. PLoS One. 2016;11(5):e0155709.
- Canto C, Houtkooper RH, Pirinen E, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-47.
- 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.
- Chen M, Huang JD, Deng HK, et al. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability. BMC Cancer. 2011;11:199.
- Lushnikova T, Bouska A, Odvody J, et al. Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene. 2011;30(46):4622-31.
- Rao CV, Asch AS, Yamada HY. Emerging links among Chromosome Instability (CIN), cancer, and aging. Mol Carcinog. 2017;56(3):791-803.
- Fatoba ST, Okorokov AL. Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation. Cell Cycle. 2011;10(14):2317-22.
- Mutafova-Yambolieva VN. Neuronal and extraneuronal release of ATP and NAD(+) in smooth muscle. IUBMB Life. 2012;64(10):817-24.
- Watroba M, Dudek I, Skoda M, et al. Sirtuins, epigenetics and longevity. Ageing Res Rev. 2017;40:11-9.
- Scitable: Cell Energy and Cell Functions.
- Oka S, Hsu CP, Sadoshima J. Regulation of cell survival and death by pyridine nucleotides. Circ Res. 2012;111(5):611-27.
- Rowlands BD, Lau CL, Ryall JG, et al. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism. J Neurosci Res. 2015;93(7):1147-56.
- Hung CH, Chan SH, Chu PM, et al. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res. 2015;59(10):1905-17.
- Xiao N, Mei F, Sun Y, et al. Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in adipocytes with regulation of AMP-activated kinase and/or sirtuin 1 activity. Planta Med. 2014;80(12):993-1000.
- Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017.
- Rowlands BD, Lau CL, Ryall JG, et al. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism. J Neurosci Res. 2015;93(7):1147-56.
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