Intervention with Multiple Micronutrients Including Dietary and Endogenous Antioxidants for Healthy Aging

Abstract

Many studies suggest that increased oxidative stress and chronic inflammation are associated with aging in all species, including humans. Growing evidence suggests that these two biological events contribute directly to age-associated decline in organ function. The degenerative changes in the cells are initiated by oxidative damage to mitochondria, which produce more free radicals, which reduce proteasome activity, length of telomere, and immune function and improve lysosomal proteolytic activity. The plasma levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) also increase with aging and contribute to the loss of muscle mass and muscle strength. Limited data show that an adaptive response of antioxidant enzymes to increased oxidative stress occurs in rodents but not in humans. In rodents, plasma vitamin C and tissue coenzyme Q10 levels decline, but plasma glutathione and vitamin E levels are elevated as a function of aging. In contrast, in humans the plasma level of vitamin E decreases and retinol does not change. The fact that increased activity of certain antioxidant enzymes and certain antioxidants exists in the presence of elevated levels of oxidative stress and chronic inflammation suggests that the increased levels of antioxidant systems within the physiologic range may not be sufficient to downregulate the level of oxidative stress and chronic inflammation. Doses of antioxidants higher than those within the physiologic range are needed to reduce oxidative stress and chronic inflammation. This is supported by the fact that the individual antioxidants at high doses reduce the rate of aging. For example, supplementation with individual antioxidants such as vitamin E, coenzyme Q10, carotenoids, melatonin, flavonoids, glutathione-elevating agents (N-acetylcysteine), α-lipoic acid, and acetyl-l-carnitine decreased the rate of age-related decline in organ function by reducing oxidative stress and chronic inflammation in rodents. Additional studies on the activities of antioxidant enzymes and levels of dietary and endogenous antioxidants as a function of aging are needed. In the meantime, the author recommends consumption of multiple micronutrients including high doses of dietary and endogenous antioxidants together with changes in diet and lifestyle for maintaining healthy aging. Multiple antioxidants are recommended because many different types of free radicals are produced, and each antioxidant has a different affinity for each of these free radicals, depending upon the cellular environment. In addition, they are distributed differently in different organs and in subcellular compartments within the same cell and exhibit different mechanisms of action.