Growing Old With Zinc

If you read—and were enlightened by—the newsletter about aging and omega-3 fatty acids, you’ll likely be interested in this one about zinc and its relationship to aging and disease. For a long time, zinc has been associated with a strong immune system, but its connection to aging is a relatively new exploration. Whether zinc deficiency promotes aging or results from it matters little to those who endure its aftermath in their “golden” years.

What Is This Stuff?

Zinc is a mineral essential to all life. In humans, it plays a functional role in immunity, in growth and development, in neurological mechanisms, and in reproduction, as well as in several avenues of cellular metabolism. It performs a structural role in some proteins as a stabilizer and in cell membranes as a guard against oxidative insults and functional impairment (O’Dell, 2000). Additionally, zinc is a component of “zinc fingers,” which are structural domains that are wrapped around a zinc ion and regulate gene expression by acting as transcription factors by cleaving to DNA. Zinc has been found to be integral to programmed cell death, called apoptosis (Truong-Tran, 2000).

Do I Have Enough?

Possibly not. The World Health Organization (WHO) suggests that zinc deficiency is widespread and affects the health and well-being of populations worldwide. The International Zinc Nutrition Consultative group (IZiNCG) has determined that zinc intake is inadequate based on the presence and bioavailability of this micro-nutrient in each country’s food supply. Deficiency in children, especially, raises the risk for diarrheal diseases, pneumonia and malaria, the latter a defined danger for populations so exposed (WHO, 2008). Conservative estimates posit that one-fourth of the world’s population is deficient in zinc (Maret, 2006).

Although zinc deficiency is typically diet-related, it can spring from malabsorption, chronic liver and kidney disease, sickle-cell disease, diabetes, malignancy, and as a result of bariatric surgery, heavy metal exposure and possibly the ingestion of FD&C Yellow #5, known as tartrazine (GPN, 2012). The problem of zinc deficiency has been known for decades, but has received scant attention because it was believed that it could never occur in humans (Prasad, 2003). Yet its burden is outstanding and simply resolved with supplementation. The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because meat is not part of the vegan regimen. The legumes and plants common to vegetarian diets contain phytates that bind zinc and inhibit its absorption (Hunt, 2003) (Sandstrom, 1997) (Wise, 1995). Considering that poor agricultural, storage, shipping and kitchen practices can take a toll on any food’s nutritional profile, it can readily be seen that deficit is not the impossibility it once was thought to be. Eleven milligrams a day for an adult male and nine for a female is enough to meet nutritional requirements. Doses for children and pregnant women may be retrieved from the Office of Dietary Supplements at the National Institute of Health website (IOM, 2001).

What About Aging?

As we age, our DNA replication may become increasingly undependable because of shortened telomeres, possibly setting the stage for chronic, debilitating diseases, including cancer. There is a substantial body of evidence suggesting that a significant percentage of cancer deaths could be avoided by paying attention to proper nutrition.  Only in this century has zinc been tagged as a vital element in host defense against the initiation and progression of this disease, based partly on zinc’s character as supporting more than three hundred mammalian proteins (Ho, 2004). Because cancer is a disease mostly of the middle and older years, it is fitting to maintain a healthy nutritional intake, including supplementation if needed, noting that the elder population is vulnerable to zinc deficiency.

The pertinence of zinc to the entire immune system is well-documented. The presence of chronic inflammation, whether from physical illness, oxidative stress or the mental challenges of daily asperities, may induce sub-optimal zinc levels for most of us. From this was born the recommendation that zinc be supplemented to at-risk populations, notably the aged (Mocchegiani, 2006). It has been proposed that genetic screening for response to zinc intake be considered in order to maintain a healthy immune system, to ensure the activity of anti-oxidant proteins, and to avoid the frailty and degeneration that often accompany old age (Mocchegiani, 2007).

Among the environmental bombardments suffered by the immune system is cadmium exposure, largely from fossil fuels combustion, but also from some fertilizers, metal refining, and tobacco use. Smokers have four times the cadmium levels as non-smokers, and this may be causative of early atherosclerosis and hypertension, both being risk factors for CVD, but also attenuated by high zinc concentrations (Messner, 2009). The long biological half-life of cadmium only compounds the concerns by presenting a cumulative effect, resulting in sterilizing, teratogenic and carcinogenic ramifications (Bin, 1994). The physical attack from cadmium and cohort environmental insults may lead to a state termed immunosenescence, the gradual deterioration of the immune system brought on by natural age advancement. As soon as you agree that, “Hey, this is just the way it is,” you have already decided to lose the race by a considerable margin. A large part of the aging drama can be explained by an imbalance between pro- and anti-inflammatory complexes, most often resulting in low-grade chronic inflammation. This condition is a driving force behind the frailty and the more common conditions associated with aging (Franceschi, 2007).  The Third Zinc Age Meeting in Madrid offered that zinc supplementation presents a strong case in the management of healthy aging (Mocchegiani, 2006), since  zinc deficiency is constantly observed in the chronic inflammation of old age (Vasto, 2007) (Fabris, 1995).

The absolute requirement for zinc is not known to be higher in the elderly, buttheir intake tends to be low. There are social factors that can interfere withsound dietary habits, loneliness being paramount. Insufficient intake of zinc(from food or supplements) may lead to loss of taste sensation, which leads tounwillingness to eat, which continues the vicious cycle. Drugs that promote zincexcretion (including some diuretics), poor absorption and chronic diseases contributeto the deficit. Although it might not turn back the clock, zinc may be able toslow its forward progression.

Bin QH, Garfinkel D. The cadmium toxicity hypothesis of aging: a possible explanation for the zinc deficiency hypothesis of aging. Med Hypotheses. 1994 Jun;42(6):380-4.

Daaboul D, Rosenkranz E, Uciechowski P, Rink L. Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells. Metallomics. 2012 Oct 1;4(10):1088-97. Epub 2012 Sep 14.

Fabris N, Mocchegiani E. Zinc, human diseases and aging. Aging (Milano). 1995 Apr;7(2):77-93.

Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007 Jan;128(1):92-105. Epub 2006 Nov 20.

Garfinkel D. Is aging inevitable? The intracellular zinc deficiency hypothesis of aging. Med Hypotheses. 1986 Feb;19(2):117-37.

GPN--General Practice Notebook--a UK Medical reference http://www.gpnotebook.co.uk/simplepage.cfm?ID=886046736 Accessed 15 October, 2012

Emily Ho Zinc deficiency, DNA damage and cancer risk The Journal of Nutritional Biochemistry. Vol 15, Iss 10 , PP 572-578, Oct 2004

Andrea Hönscheid, Svenja Dubben, Lothar Rink, Hajo Haas Zinc differentially regulates mitogen-activated protein kinases in human T cells The Journal of Nutritional Biochemistry. Vol 23, Iss 1 , Pp 18-26, Jan 2012

Hunt JR. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr. 2003 Sep;78(3 Suppl):633S-639S. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001. http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/#en2

Mahoney MG, Brennan D, Starcher B, Faryniarz J, Ramirez J, Parr L, Uitto J. Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis. Exp Dermatol. 2009 Mar;18(3):205-11.

Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol. 2006;20(1):3-18. Epub 2006 Feb 21.

Messner B, Knoflach M, Seubert A, Ritsch A, Pfaller K, Henderson B, Shen YH, Zeller I, Willeit J, Laufer G, Wick G, Kiechl S, Bernhard D. Cadmium is a novel and independent risk factor for early atherosclerosis mechanisms and in vivo relevance. Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1392-8.

Mocchegiani E, Malavolta M, Marcellini F, Pawelec G. Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing. Immun Ageing. 2006 Jun 26;3:6.

Mocchegiani E. Zinc and ageing: third Zincage conference. Immun Ageing. 2007 Sep 20;4:5.

O'Dell BL. Role of zinc in plasma membrane function. J Nutr. 2000 May;130(5S Suppl):1432S-6S.

Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M. Zinc deficiency in elderly patients. Nutrition. 1993 May-Jun;9(3):218-24.

Prasad AS. Zinc deficiency. BMJ. 2003 Feb 22;326(7386):409-10.

Sandström B. Bioavailability of zinc. Eur J Clin Nutr. 1997 Jan;51 Suppl 1:S17-9.

Truong-Tran AQ, Ho LH, Chai F, Zalewski PD. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J Nutr. 2000 May;130(5S Suppl):1459S-66S.

Vasto S, Mocchegiani E, Malavolta M, Cuppari I, Listì F, Nuzzo D, Ditta V, Candore G, Caruso C. Zinc and inflammatory/immune response in aging. Ann N Y Acad Sci. 2007 Apr;1100:111-22.

Wise A. Phytate and zinc bioavailability. Int J Food Sci Nutr. 1995 Feb;46(1):53-63.

Carmen P. Wong, Kathy R. Magnusson, Emily Ho Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation The J of Nutr Biochem. Article in Press--published online 17 September 2012.

World health Organization. Published Online: 17 January 2008 Comparative Quantification of Health Risks Childhood and maternal undernutrition Chapter 5: Zinc deficiency Laura E. Caulfield and Robert E. Black http://www.who.int/publications/cra/chapters/volume1/part2/en/index.html

Zatta P, Lucchini R, van Rensburg SJ, Taylor A. The role of metals in neurodegenerative processes: aluminum, manganese, and zinc. Brain Res Bull. 2003 Nov 15;62(1):15-28.