Life Extension Magazine®
NAD+ is a coenzyme found in all living cells. It is essential for energy production and DNA repair.1-3
In 2014, we introduced a NAD+ precursor called nicotinamide riboside.4 When you take nicotinamide riboside, it converts to NAD+ in your cells, where it facilitates regenerative processes.5
The most important NAD+ benefit is promoting rapid DNA repair and fueling beneficial longevity proteins.2,3,6,7
Resveratrol favorably enhances the activation of cellular sirtuin proteins.8 NAD+ is required for our sirtuins to function.7,9,10
As we age, NAD+ levels plummet, which impedes the ability of resveratrol to deliver its benefits.11-14
In 2003, we introduced resveratrol based on its ability to activate sirtuin longevity factors.15,16
Genetic research we conducted back then indicated that biologically meaningful resveratrol dosing for humans might be as low as 20 mg a day.16,17 Subsequent studies suggested higher resveratrol intake.18,19
Based on our interpretation of emerging evidence, we have reformulated our premium supplements to provide more NAD+ precursor (nicotinamide riboside) with lower resveratrol.
You’re going to learn about potential age-reversal benefits of boosting cellular NAD+ later this year. This article will provide a summary of what’s been uncovered in recent published studies.
NAD+ is required for healthy cellular functions including DNA repair.1-3
The amount of damage inflicted to cellular DNA is grossly underestimated. Be it background radiation or normal metabolic processes, our DNA is constantly “broken” and then “repaired” using specialized coenzymes like NAD+.
Failure to repair damaged DNA can result in cell death or transformation into malignant or senescent states.
NAD+ levels markedly decline with age.11-14 NAD+ deficit manifests clinically in the form of degenerative disorders of the brain,20-23 heart,24-26 and other tissues.27,28
In animal studies, regenerative effects have been observed in the brain when NAD+ is restored.29,30
Sleep quality deteriorates with normal aging in many people. Restoring youthful NAD+ levels in the brain may support a healthy circadian rhythm.31
Loss of NAD+ activity is linked to type II diabetes. In mice, administration of an NAD+ precursor restores insulin sensitivity and protects against the diabetic impact of a high-fat diet.6,32,33
Resveratrol and NAD+
Resveratrol has become a popular dietary supplement because of its ability to activate sirtuin proteins in our cells.34
When sirtuins are activated, the effect is delayed aging, which has been demonstrated in a wide spectrum of experimental models, including mammals.35-44
Sirtuins that are activated by resveratrol require NAD+ as their energy substrate. Loss of NAD+ impedes beneficial sirtuin function.7,10,45
Younger people have high NAD+ levels that enable them to benefit from the sirtuin-boosting effects of resveratrol.
To improve the functionality of sirtuin proteins, it makes sense for maturing individuals to boost their NAD+ levels.
The good news is that a precursor to NAD+ can be found in nicotinamide riboside supplements. New dosage recommendations can enable older people to restore cellular NAD+ to more youthful profiles.
NAD+ Benefits More Than Just Sirtuins
The favorable effect of resveratrol in promoting sirtuin activity is well established. For sirtuins to function properly, they must have sufficient NAD+ to fuel their activity.7,10
Protecting against pathological aging, however, requires more than securing sirtuin structure-function. We must also ensure the following two types of DNA damage are repaired:
- Single-strand DNA breaks occur often and are usually fixed by nutrients that most of you supplement with today.
- Double-strand DNA breaks are more difficult to restore. Left unrepaired, double-strand breaks create cellular havoc that can lead to systemic degeneration.
A critical enzyme that repairs double-strand DNA breaks is PARP1.46-48 For the PARP1 enzyme to function it requires lots of NAD+.49,50
When it comes to protecting against cancer, a tumor suppressor called p53 protects against runaway cell propagation.
NAD+ supports p53 activation to help thwart malignant transformation.51-53
Nutrients That Facilitate DNA Repair
People seeking to extend their lifespans today avoid toxins (such as tobacco smoke and overcooked food) that damage DNA.
Vitamin D has been shown to play an important role in DNA repair, which helps explain why people with higher levels of vitamin D show lower rates of most degenerative diseases.70,76-78
Folic acid also plays a role in maintaining certain DNA repair mechanisms.79-85
Many of the supplements we take daily help facilitate DNA repair. The box below provides a partial listing of these nutrients.
Up until now, no nutrient could accelerate DNA repair to the magnitude needed to induce possible age-reversal benefits. That may have changed based on data showing remarkable DNA repair occurring when the amount of NAD+ (nicotinamide adenine dinucleotide) is increased in our cells.3,86
DNA Repair Activators |
||||
Fish Oil87-89 | Vitamin B1290 | Vitamin E91 | Vitamin C92 | Nicotinamide86 |
CoQ1093 | Zinc94 | Magnesium95,96 | Selenium97 | Polyphenols98-100 |
Grape Seed Extract101,102 | Curcumin103,104 | Carotenoids105-107 | Vitamin B6108,109 |
Magnitude of Daily DNA Damage
Few people understand the degree of daily damage inflicted to their cellular DNA.
To put this into perspective, a study analyzed how many double-stranded DNA breaks occur per cell each day. The number turned out to be 10 DNA breaks per cell every day.54
Your cells require NAD+ to facilitate repair of DNA breaks. Sufficient NAD+ is needed for the PARP1 repair enzyme to function.49,50,55
Imagine every dividing cell in your body undergoing ten double-stranded DNA breaks per day and NOT being repaired because your NAD+ is depleted from aging, or from outside abuse such as excess alcohol and toxic food ingestion.
It explains many degenerative pathologies that occur as aging cells lose their NAD+.
Repairing DNA breaks will probably go a long way towards preventing cells from turning malignant. That’s because NAD+ helps maintain activity of cell division regulators like p53.51-53
Restoring Youthful Cell Functionality
As we age, beneficial genes that support cell health “turn off” while detrimental genes overexpress.
Nutrients like curcumin help suppress genes that generate system-wide inflammation.56-59
Likewise, omega-3s60-66 and vitamin D67-70 favorably impact hundreds of genes that protect against degenerative illnesses.
To reverse the accumulation of damage inflicted to cellular DNA, we should support the efficient function of PARP1 enzymes.
PARP1 facilitates DNA repair via multiple mechanisms.
Higher NAD+ cell levels enable PARP1 to function properly.49,71,72
Aging creates a chaotic environment in the brain that can make sound sleep difficult.73 As DNA is repaired, we regain youthful cell functionality that can result in improved overall health.
Combining resveratrol with more nicotinamide riboside supports healthy cellular NAD+ levels,73 which are important to support anti-aging enymes like PARP1 and BubR1.71,74,75
BubR1 is an enzyme that protects against chromosome instability. According to one study, sustained high-level expression of BubR1 “provides a unique opportunity to extend healthy lifespan”.75
Some of you may find these new acronyms like PARP1 a bit confusing.
I hope you appreciate (as I do) how rapidly our understanding of aging is expanding, along with accessible ways to reverse many degenerative changes.
Take Control by Boosting Your NAD+
George Church, PhD, is a Harvard professor pioneering CRISPR/Cas9 gene editing technology.110,111
Once perfected, Dr. Church has publicly stated that this will enable aging humans to “edit” their genes in a way that will empower them to regain youth.
We’ve reported on Dr. Church’s research in past issues of Life Extension Magazine®.110,111 This age-reversal gene-editing technology is predicted to be perfected in the next 5-10 years.
In the meantime, we can exert significant control over cellular health factors by taking more nicotinamide riboside. This will boost NAD+ blood levels several fold.5
How our genes are expressed and their stability determines whether we retain healthy vitality or suffer relentless degeneration.
Nutrients like curcumin,112,113 fish oil,60-63 folate,114-116 and vitamin D70,117-119 promote youthful genomic stability.
The box below displays additional benefits one can obtain by boosting cellular NAD+.
This can be accomplished by supplementing with 250 mg each day of nicotinamide riboside that converts to NAD+ in your body.
We may recommend higher nicotinamide riboside doses in coming months as scientific data emerges.
For longer life,
William Faloon, Co-Founder
Life Extension Foundation
Buyers Club
What Should Cancer Patients Being Treated With Chemo or Radiation Therapy Do?
Cancer chemotherapy drugs function via several destructive mechanisms, but the ultimate objective is to inflict massive damage to DNA so that cancer cells are destroyed. Radiation does this by directly breaking DNA strands.
One way cancer cells escape complete eradication after exposure to chemotherapy or radiation is to repair damaged DNA via a wide range of survival mechanisms.
Some studies suggest adding “DNA repair inhibitor” drugs might enable conventional chemo/radiation therapies to kill more cancer cells.
The downside to DNA repair inhibitors is they might increase the toxicity of chemo/radiation therapy to healthy cells and thus create more serious side effects. To cite a conclusion from a published study on this topic:
“With the addition of DNA repair inhibitors, standard chemotherapy could become more effective but also more toxic.”120
What the above conclusion alludes to is that adding drugs that impede DNA repair might make chemotherapy more effective, but in the process make the chemotherapy more toxic. A major limiting factor to chemotherapy is toxicity so severe that patients are forced to discontinue therapy even when it is demonstrating efficacy.
For example, one of many toxic side effects of chemotherapy is painful neuropathy.121-124 Cancer patients who take steps to boost their NAD+ levels have experienced relief from fatigue.125 Animals given nicotinamide riboside experienced reductions in chemotherapy-induced neuropathy.126
Another side effect of certain chemotherapy drugs and radiation to the chest is heart failure.127-132 Nutrients like coenzyme Q10 have been shown to protect against this cardiac damage133-135 and improve survival in cancer patients.136-139 Conventional oncologists are largely unaware of this clinical research.
As it relates to supplementation with higher-dose nicotinamide riboside, we’ve reviewed numerous published studies and it is not possible to reach a rational consensus as to what actively-treated cancer patients should do as it relates to boosting their cellular NAD+.
Out of an abundance of caution, we suggest cancer patients undergoing chemotherapy or radiation avoid higher-dose NAD+ during therapy and for a reasonable period after.
The conundrum cancer patients have faced for decades are arguments from many oncologists to take no supplements during chemo/radiation therapy. The concern is the nutrients might protect malignant cells from destruction.
Opposing this conventional view are numerous studies demonstrating that nutritional and herbal supplements do not interfere with the effectiveness of chemotherapy or radiation therapy. Furthermore, a myriad of controlled studies show marked survival improvements when cancer patients supplement with nutrients that boost immune function and protect against treatment side effects.140-159
Stated simply, malignant cells can preferentially “hijack” many of the same factors healthy cells require for survival. There is thus a delicate theoretical balance as to what cancer patients should do during conventional treatment. For updated guidance on nutrients, hormones and off-label drugs that actively-treated cancer patients should consider, refer to our updated protocols at:
www.LifeExtension.com/Chemotherapy
and
www.LifeExtension.com/Radiation
References
- Busso N, Karababa M, Nobile M, et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One. 2008;3(5):e2267.
- Canto C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. (References continued on page 12.)
- Satoh MS, Poirier GG, Lindahl T. NAD(+)-dependent repair of damaged DNA by human cell extracts. J Biol Chem. 1993;268(8):5480-7.
- Available at: http://www.lifeextension.com/Magazine/2014/11/The-Youth-Restoring-Benefits-Of-NAD/Page-01. Accessed June 15, 2017.
- Trammell SA, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948.
- 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.
- Canto C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev. 2012;64(1): 166-87.
- Lekli I, Ray D, Das DK. Longevity nutrients resveratrol, wines and grapes. Genes Nutr. 2010;5(1):55-60.
- Landry J, Sutton A, Tafrov ST, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000;97(11):5807-11.
- Villalba JM, Alcain FJ. Sirtuin activators and inhibitors. Biofactors. 2012;38(5):349-59.
- Guest J, Grant R, Mori TA, et al. Changes in oxidative damage, inflammation and [NAD(H)] with age in cerebrospinal fluid. PLoS One. 2014;9(1):e85335.
- Massudi H, Grant R, Braidy N, et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357.
- Stein LR, Imai S. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. Embo j. 2014;33(12):1321-40.
- Braidy N, Guillemin GJ, Mansour H, et al. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One. 2011;6(4):e19194.
- Available at: http://www.lifeextension.com/Magazine/2008/2/Living-Longer-Healthier-Lives-With-Resveratrol/Page-01. Accessed June 15, 2015.
- Available at: http://www.lifeextension.com/magazine/2007/3/report_resveratrol/page-01. Accessed June 15, 2017.
- Available at: http://www.lifeextension.com/magazine/2006/7/report_longevity/Page-01. Accessed July 5, 2017.
- Dash S, Xiao C, Morgantini C, et al. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013;33(12):2895-901.
- Kennedy DO, Wightman EL, Reay JL, et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91(6):1590-7.
- Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-71.
- Liu D, Pitta M, Mattson MP. Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restriction. Ann N Y Acad Sci. 2008;1147:275-82.
- Min SW, Sohn PD, Cho SH, et al. Sirtuins in neurodegenerative diseases: an update on potential mechanisms. Front Aging Neurosci. 2013;5:53.
- Anekonda TS, Reddy PH. Neuronal protection by sirtuins in Alzheimer’s disease. J Neurochem. 2006;96(2):305-13.
- Borradaile NM, Pickering JG. NAD(+), sirtuins, and cardiovascular disease. Curr Pharm Des. 2009;15(1):110-7.
- Hsu CP, Oka S, Shao D, et al. Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circ Res. 2009;105(5):481-91.
- Pillai VB, Sundaresan NR, Kim G, et al. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem. 2010;285(5):3133-44.
- 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):269-82.
- Zhou CC, Yang X, Hua X, et al. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016;173(15):2352-68.
- Zhao Y, Guan YF, Zhou XM, et al. Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase-Nicotinamide Adenine Dinucleotide Cascade. Stroke. 2015;46(7):1966-74.
- 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.
- Imai S. “Clocks” in the NAD World: NAD as a metabolic oscillator for the regulation of metabolism and aging. Biochim Biophys Acta. 2010;1804(8):1584-90.
- Yoshino J, Mills KF, Yoon MJ, et al. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-36.
- Trammell SA, Weidemann BJ, Chadda A, et al. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016;6:26933.
- Higashida K, Kim SH, Jung SR, et al. Effects of resveratrol and SIRT1 on PGC-1alpha activity and mitochondrial biogenesis: a reevaluation. PLoS Biol. 2013;11(7):e1001603.
- Rehan L, Laszki-Szczachor K, Sobieszczanska M, et al. SIRT1 and NAD as regulators of ageing. Life Sci. 2014;105 (1-2):1-6.
- Imai S-i, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017.
- Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013;154(2):430-41.
- Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13(19):2570-80.
- Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004;101(45):15998-6003.
- Giblin W, Skinner ME, Lombard DB. Sirtuins: guardians of mammalian healthspan. Trends Genet. 2014;30(7):271-86.
- Satoh A, Brace CS, Rensing N, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 2013;18(3):416-30.
- Satoh A, Imai S. Systemic regulation of mammalian ageing and longevity by brain sirtuins. Nat Commun. 2014;5:4211.
- Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004;305(5686):1010-3.
- Schmeisser K, Mansfeld J, Kuhlow D, et al. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol. 2013;9(11):693-700.
- Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253-95.
- Mao Z, Hine C, Tian X, et al. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011;332(6036):1443-6.
- Hochegger H, Dejsuphong D, Fukushima T, et al. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. Embo j. 2006;25(6):1305-14.
- Paddock MN, Buelow BD, Takeda S, et al. The BRCT domain of PARP-1 is required for immunoglobulin gene conversion. PLoS Biol. 2010;8(7):e1000428.
- Kim MY, Zhang T, Kraus WL. Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev. 2005;19(17):1951-67.
- Siegel C, McCullough LD. NAD+ depletion or PAR polymer formation: which plays the role of executioner in ischaemic cell death? Acta Physiol (Oxf). 2011;203(1):225-34.
- Langley E, Pearson M, Faretta M, et al. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. Embo j. 2002;21(10):2383-96.
- Pfister NT, Yoh KE, Prives C. p53, DNA damage, and NAD+ homeostasis. Cell Cycle. 2014;13(11):1661-2.
- McLure KG, Takagi M, Kastan MB. NAD+ modulates p53 DNA binding specificity and function. Mol Cell Biol. 2004;24(22):9958-67.
- Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:181-211.
- El Ramy R, Magroun N, Messadecq N, et al. Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes. Cell Mol Life Sci. 2009;66(19):3219-34.
- Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995;270(42):24995-5000.
- Ranjan D, Chen C, Johnston TD, et al. Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFkappaB activation, and IL-2 signaling. J Surg Res. 2004;121(2):171-7.
- Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2004;1030:434-41.
- Kumar A, Dhawan S, Hardegen NJ, et al. Curcumin (Diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation. Biochem Pharmacol. 1998;55(6):775-83.
- Bouwens M, van de Rest O, Dellschaft N, et al. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009;90(2):415-24.
- Weaver KL, Ivester P, Seeds M, et al. Effect of dietary fatty acids on inflammatory gene expression in healthy humans. J Biol Chem. 2009;284(23):15400-7.
- Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr. 2001;131(4):1129-32.
- Gillies PJ, Bhatia SK, Belcher LA, et al. Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil. J Lipid Res. 2012;53(8):1679-89.
- Thomas J, Thomas CJ, Radcliffe J, et al. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease. Biomed Res Int. 2015;2015:172801.
- Dyall SC, Michael GJ, Michael-Titus AT. Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. J Neurosci Res. 2010;88(10):2091-102.
- Kitajka K, Puskas LG, Zvara A, et al. The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci U S A. 2002;99(5):2619-24.
- Chakraborti CK. Vitamin D as a promising anticancer agent. Indian J Pharmacol. 2011;43(2):113-20.
- Li H, Stampfer MJ, Hollis JB, et al. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007;4(3):e103.
- Bao BY, Yao J, Lee YF. 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis. 2006;27(9):1883-93.
- Hossein-nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725.
- Schiewer MJ, Knudsen KE. Transcriptional roles of PARP1 in cancer. Mol Cancer Res. 2014;12(8):1069-80.
- Everson CA, Henchen CJ, Szabo A, et al. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats. Sleep. 2014;37(12):1929-40.
- Mouchiroud L, Houtkooper RH, Auwerx J. NAD(+) metabolism, a therapeutic target for age-related metabolic disease. Critical reviews in biochemistry and molecular biology. 2013;48(4):10.3109/10409238.2013.789479.
- North BJ, Rosenberg MA, Jeganathan KB, et al. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. The EMBO Journal. 2014;33(13):1438-53.
- Baker DJ, Dawlaty MM, Wijshake T, et al. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nat Cell Biol. 2013;15(1):96-102.
- Halicka HD, Zhao H, Li J, et al. Attenuation of constitutive DNA damage signaling by 1,25-dihydroxyvitamin D3. Aging (Albany NY). 2012;4(4):270-8.
- Available at: http://www.lifeextension.com/magazine/2013/8/The-Overlooked-Importance-of-Vitamin-D-Receptors/Page-01. Accessed June 16, 2017.
- Fleet JC, DeSmet M, Johnson R, et al. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441(1):61-76.
- Ames BN. A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys. 2004;423(1): 227-34.
- Wei Q, Shen H, Wang LE, et al. Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomarkers Prev. 2003;12(10):963-9.
- Duthie SJ. Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis. J Inherit Metab Dis. 2011;34(1):101-9.
- Basten GP, Duthie SJ, Pirie L, et al. Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Br J Cancer. 2006;94(12):1942-7.
- Choi SW, Kim YI, Weitzel JN, et al. Folate depletion impairs DNA excision repair in the colon of the rat. Gut. 1998;43(1):93-9.
- Kruman, II, Kumaravel TS, Lohani A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci. 2002;22(5):1752-62.
- Sadik NA, Shaker OG. Dietary folate suppresses DMH-induced colon carcinogenesis in a rat model and affects DMH-induced expression of four DNA repair enzymes. Nutr Cancer. 2012;64(8):1196-203.
- Surjana D, Halliday GM, Damian DL. Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair. Journal of Nucleic Acids. 2010;2010:13.
- Hong MY, Lupton JR, Morris JS, et al. Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation. Cancer Epidemiol Biomarkers Prev. 2000;9(8):819-26.
- Ghorbanihaghjo A, Safa J, Alizadeh S, et al. Protective effect of fish oil supplementation on DNA damage induced by cigarette smoking. J Health Popul Nutr. 2013;31(3):343-9.
- Stephenson JA, Al-Taan O, Arshad A, et al. The multifaceted effects of omega-3 polyunsaturated Fatty acids on the hallmarks of cancer. J Lipids. 2013;2013:261247.
- Alzoubi K, Khabour O, Hussain N, et al. Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone. Mutat Res. 2012;748(1-2):48-51.
- Sweetman SF, Strain JJ, McKelvey-Martin VJ. Effect of antioxidant vitamin supplementation on DNA damage and repair in human lymphoblastoid cells. Nutr Cancer. 1997;27(2):122-30.
- Cooke MS, Evans MD, Podmore ID, et al. Novel repair action of vitamin C upon in vivo oxidative DNA damage. FEBS Lett. 1998;439(3):363-7.
- Tomasetti M, Alleva R, Borghi B, et al. In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage. Faseb j. 2001;15(8):1425-7.
- Song Y, Leonard SW, Traber MG, et al. Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats. J Nutr. 2009;139(9):1626-31.
- Hartwig A. Role of magnesium in genomic stability. Mutat Res. 2001;475(1-2):113-21.
- Mahabir S, Wei Q, Barrera SL, et al. Dietary magnesium and DNA repair capacity as risk factors for lung cancer. Carcinogenesis. 2008;29(5):949-56.
- de Rosa V, Erkekoglu P, Forestier A, et al. Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCaP prostate cancer cells. Free Radic Res. 2012;46(2):105-16.
- Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010;302(2):71-83.
- Zattra E, Coleman C, Arad S, et al. Polypodium leucotomos extract decreases UV-induced Cox-2 expression and inflammation, enhances DNA repair, and decreases mutagenesis in hairless mice. Am J Pathol. 2009;175(5):1952-61.
- Tan X, Zhao C, Pan J, et al. In vivo non-enzymatic repair of DNA oxidative damage by polyphenols. Cell Biol Int. 2009;33(6):690-6.
- Katiyar SK, van Steeg H, Sharma SD. Abstract 1875: Dietary grape seed proanthocyanidins induce rapid repair of DNA damage via nucleotide excision repair genes in preventing UV-induced immunosuppression. Cancer Research. 2010;70(8 Supplement):1875-.
- Mansouri E, Khorsandi L, Abedi HA. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats. Iran J Basic Med Sci. 2014;17(6):460-4.
- Roy M, Sinha D, Mukherjee S, et al. Curcumin prevents DNA damage and enhances the repair potential in a chronically arsenic-exposed human population in West Bengal, India. Eur J Cancer Prev. 2011;20(2):123-31.
- Mukherjee S, Roy M, Dey S, et al. A Mechanistic Approach for Modulation of Arsenic Toxicity in Human Lymphocytes by Curcumin, an Active Constituent of Medicinal Herb Curcuma longa Linn. J Clin Biochem Nutr. 2007;41(1):32-42.
- Astley SB, Elliott RM, Archer DB, et al. Increased cellular carotenoid levels reduce the persistence of DNA single-strand breaks after oxidative challenge. Nutr Cancer. 2002;43(2):202-13.
- Lorenzo Y, Azqueta A, Luna L, et al. The carotenoid beta-cryptoxanthin stimulates the repair of DNA oxidation damage in addition to acting as an antioxidant in human cells. Carcinogenesis. 2009;30(2):308-14.
- Astley SB, Elliott RM, Archer DB, et al. Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage: repair balance in human lymphocytes. Br J Nutr. 2004;91(1):63-72.
- Chou YC, Chu CH, Wu MH, et al. Dietary intake of vitamin B(6) and risk of breast cancer in Taiwanese women. J Epidemiol. 2011;21(5):329-36.
- Le Marchand L, White KK, Nomura AM, et al. Plasma levels of B vitamins and colorectal cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2009;18(8):2195-201.
- Available at: http://www.lifeextension.com/Magazine/2014/6/The-2013-SENS-Foundation-Conference/Page-01. Accessed June 16, 2017.
- Available at: http://www.lifeextension.com/Magazine/2016/7/Age-Reversal-Research-at-Harvard-Medical-School/Page-01. Accessed June 16, 2017.
- Thomas P, Wang YJ, Zhong JH, et al. Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for Alzheimer’s disease. Mutat Res. 2009;661(1-2):25-34.
- Shu L, Khor TO, Lee JH, et al. Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells. Aaps j. 2011;13(4):606-14.
- Bistulfi G, Vandette E, Matsui S, et al. Mild folate deficiency induces genetic and epigenetic instability and phenotype changes in prostate cancer cells. BMC Biol. 2010;8:6.
- Duthie SJ, Narayanan S, Sharp L, et al. Folate, DNA stability and colo-rectal neoplasia. Proc Nutr Soc. 2004;63(4):571-8.
- James SJ, Pogribny IP, Pogribna M, et al. Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis. J Nutr. 2003;133(11 Suppl 1):3740s-7s.
- Palmer HG, Sanchez-Carbayo M, Ordonez-Moran P, et al. Genetic signatures of differentiation induced by 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res. 2003;63(22):7799-806.
- Fernandez-Garcia NI, Palmer HG, Garcia M, et al. 1alpha,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells. Oncogene. 2005;24(43):6533-44.
- Stefanska B, Salame P, Bednarek A, et al. Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 2012;107(6):781-90.
- Kelley MR, Logsdon D, Fishel ML. Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncol. 2014;10(7):1215-37.
- Park HJ. Chemotherapy induced peripheral neuropathic pain. Korean J Anesthesiol. 2014;67(1):4-7.
- Piccolo J, Kolesar JM. Prevention and treatment of chemotherapy-induced peripheral neuropathy. Am J Health Syst Pharm. 2014;71(1):19-25.
- Visovsky C, Collins M, Abbott L, et al. Putting evidence into practice: evidence-based interventions for chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs. 2007;11(6):901-13.
- Stubblefield MD, McNeely ML, Alfano CM, et al. A prospective surveillance model for physical rehabilitation of women with breast cancer: chemotherapy-induced peripheral neuropathy. Cancer. 2012;118(8 Suppl):2250-60.
- Feedback from chemotherapy patients using nicotinamide riboside dietary supplements. Life Extension Wellness Specialist Report. June 2017.
- Hamity MV, White SR, Walder RY, et al. Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats. Pain. 2017;158(5): 962-72.
- Available at: http://www.health.harvard.edu/heart-health/cancer-treatments-may-harm-the-heart. Accessed June 16, 2017.
- Available at: https://www.texasoncology.com/cancer-treatment/side-effects-of-cancer-treatment/long-term-side-effects/cardiac-toxicity. Accessed June 16, 2017.
- Svoboda M, Poprach A, Dobes S, et al. Cardiac toxicity of targeted therapies used in the treatment for solid tumours: a review. Cardiovasc Toxicol. 2012;12(3):191-207.
- Marinko T, Dolenc J, Bilban-Jakopin C. Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. Radiol Oncol. 2014;48(2):105-12.
- Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-98.
- Yusuf SW, Sami S, Daher IN. Radiation-induced heart disease: a clinical update. Cardiol Res Pract. 2011;2011:317659.
- Cortes EP, Gupta M, Chou C, et al. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep. 1978;62(6):887-91.
- Iarussi D, Auricchio U, Agretto A, et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol Aspects Med. 1994;15 Suppl:s207-12.
- Albini A, Pennesi G, Donatelli F, et al. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102(1):14-25.
- Rusciani L, Proietti I, Paradisi A, et al. Recombinant interferon alpha-2b and coenzyme Q10 as a postsurgical adjuvant therapy for melanoma: a 3-year trial with recombinant interferon-alpha and 5-year follow-up. Melanoma Res. 2007;17(3):177-83.
- Folkers K, Brown R, Judy WV, et al. Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun. 1993;192(1):241-5.
- Lockwood K, Moesgaard S, Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun. 1994;199(3):1504-8.
- Lockwood K, Moesgaard S, Hanioka T, et al. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med. 1994;15 Suppl:s231-40.
- Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol. 1997;8(6):569-73.
- Lissoni P, Chilelli M, Villa S, et al. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003;35(1):12-5.
- Israel L, Hajji O, Grefft-Alami A, et al. Vitamin A augmentation of the effects of chemotherapy in metastatic breast cancers after menopause. Randomized trial in 100 patients. Ann Med Interne (Paris). 1985;136(7):551-4.
- Zou YH, Liu XM. Effect of astragalus injection combined with chemotherapy on quality of life in patients with advanced non-small cell lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003;23(10):733-5.
- Beer TM, Ryan CW, Venner PM, et al. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol. 2007;25(6):669-74.
- Pace A, Giannarelli D, Galie E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology. 2010;74(9):762-6.
- Rouse K, Nwokedi E, Woodliff JE, et al. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg. 1995;221(4):420-6.
- Kim SR, Jo SK, Kim SH. Modification of radiation response in mice by ginsenosides, active components of Panax ginseng. In Vivo. 2003;17(1):77-81.
- Xie FY, Zeng ZF, Huang HY. Clinical observation on nasopharyngeal carcinoma treated with combined therapy of radiotherapy and ginseng polysaccharide injection. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001;21(5):332-4.
- Kiremidjian-Schumacher L, Roy M, Glickman R, et al. Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res. 2000;73(2):97-111.
- Malmberg KJ, Lenkei R, Petersson M, et al. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin Cancer Res. 2002;8(6):1772-8.
- Kumar B, Jha MN, Cole WC, et al. D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells. J Am Coll Nutr. 2002;21(4):339-43.
- Kennedy RS, Konok GP, Bounous G, et al. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study. Anticancer Res. 1995;15(6b):2643-9.
- Todorova VK, Harms SA, Kaufmann Y, et al. Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats. Breast Cancer Res Treat. 2004;88(3):247-56.
- Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy. Cancer Lett. 2004;215(2):129-40.
- Hillman GG, Wang Y, Kucuk O, et al. Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model Mol Cancer Ther. 2004;3(10):1271-9.
- Yashar CM, Spanos WJ, Taylor DD, et al. Potentiation of the radiation effect with genistein in cervical cancer cells. Gynecol Oncol. 2005;99(1):199-205.
- Kotowski U, Heiduschka G, Brunner M, et al. Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane. Strahlenther Onkol. 2011;187(9):575-80.
- He H, Zhou X, Wang Q, et al. Does the couse of astragalus-containing chinese herbal prescriptions and radiotherapy benefit to non-small-cell lung cancer treatment: a meta-analysis of randomized trials. Evid Based Complement Alternat Med. 2013;2013:426207.
- Kwan ML, Greenlee H, Lee VS, et al. Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2011;130(1):195-205.