Metabolism is often thought of as the way our bodies process the foods we eat. We’ve all heard that a slow metabolism may lead to weight gain and that those people who never seem to struggle with weight may have fast metabolisms, but what does the word metabolism even mean and what does it affect outside of our waistlines?
Technically speaking, the word metabolism refers to all the chemical reactions that occur throughout the entire body.
It is true that many of the body’s chemical reactions control the digestion of food, but chemical reactions control so much more than that. In addition to breaking down the food we eat, chemical reactions are responsible for building or making the building blocks for essential components of the body, including proteins, DNA, blood cells, cell membranes, hormones, and steroids. Chemical reactions also process and dispose of waste products, such as those that are eliminated from the body in urine.
With these many cellular reactions and roles encompassed by the term metabolism, you might think these reactions have nothing in common. In fact, all cellular metabolism depends on nicotinamide adenine dinucleotide, or NAD. NAD is a co-enzyme found in all cells, and, without NAD, cells couldn’t live.
So is NAD just necessary for cellular metabolism or can it regulate it?
We know that NAD levels in the body decline with age and that patients with certain premature aging syndromes have lowered NAD levels.1-5 Obesity and metabolic syndrome also alter NAD levels.6 Many environmental factors whose effects may accumulate with increased age are also known to reduce NAD levels. For example, sun exposure reduces NAD levels through chemical reactions that correct DNA damage.7 NAD levels also rise and fall in a 24-hour cycle known as a circadian rhythm.8, 9 This means that when we stay up late, work at night, or travel between time zones, we may be changing our NAD levels.
All of these various ways in which we can lower NAD levels, through lifestyle and environmental exposures can affect the function of the chemical reactions that protect us and correct damage incurred from the environment, making us more susceptible to age-related physiological changes and complications. For example, if we have to work nights, NAD levels can become disrupted. We may be at greater risk for weight gain and a reduction our bodies’ ability to fight DNA damage accumulated in various cells and tissues.
These factors, among others, contribute to the advice to eat in moderation, to exercise, to get good quality sleep, and to stay active. While aging and many forms of stress are inevitable, making healthy lifestyle choices is a step we can all take to help combat NAD decline. A healthy cellular metabolism helps us maintain our youthful resilience, which may be even more exciting than just being a tool to manage our waistline.
- Zhu XH, Lu M, Lee BY, Ugurbil K, Chen W. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A. 2015;112(9):2876-81. doi: 10.1073/pnas.1417921112. PubMed PMID: 25730862; PMCID: PMC4352772.
- Gomes AP, Price NL, Ling AJ, 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. Cell. 2013;155(7):1624-38. doi: 10.1016/j.cell.2013.11.037. PubMed PMID: 24360282; PMCID: PMC4076149.
- Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, Grant R. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One. 2011;6(4):e19194. doi: 10.1371/journal.pone.0019194. PubMed PMID: 21541336; PMCID: PMC3082551.
- Scheibye-Knudsen M, Mitchell SJ, Fang EF, Iyama T, Ward T, Wang J, Dunn CA, Singh N, Veith S, Hasan-Olive MM, Mangerich A, Wilson MA, Mattson MP, Bergersen LH, Cogger VC, Warren A, Le Couteur DG, Moaddel R, Wilson DM, 3rd, Croteau DL, de Cabo R, Bohr VA. A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014;20(5):840-55. doi: 10.1016/j.cmet.2014.10.005. PubMed PMID: 25440059; PMCID: PMC4261735.
- Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. PubMed PMID: 22848760; PMCID: PMC3407129.
- Kim HJ, Kim JH, Noh S, Hur HJ, Sung MJ, Hwang JT, Park JH, Yang HJ, Kim MS, Kwon DY, Yoon SH. Metabolomic analysis of livers and serum from high-fat diet induced obese mice. J Proteome Res. 2011;10(2):722-31. doi: 10.1021/pr100892r. PubMed PMID: 21047143.
- de Murcia JM, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M, Oliver FJ, Masson M, Dierich A, LeMeur M, Walztinger C, Chambon P, de Murcia G. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci U S A. 1997;94(14):7303-7. PubMed PMID: 9207086; PMCID: PMC23816.
- Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009;324(5927):654-7. doi: 10.1126/science.1170803. PubMed PMID: 19286518.
- Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, Takahashi JS, Imai S, Bass J. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009;324(5927):651-4. doi: 10.1126/science.1171641. PubMed PMID: 19299583; PMCID: PMC2738420.
- Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. doi: 10.1038/ncomms12948. PubMed PMID: 27721479; PMCID: PMC5062546