Abstract
We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.—Si, H., Wang, X., Zhang, L., Parnell, L. D., Ahmed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.
Highlights
Aging is a progressive, systematic dysfunction of almost all organs and tissues, as well as an escalated vulnerability to environmental challenges
We found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle
We found that 791 genes in old control (OC) mice displayed significant expression changes (599 decreased, 192 increased) compared with young control (YC) mice, and 222 genes in EC mice were significantly different compared with OC mice
Summary
Systematic dysfunction of almost all organs and tissues, as well as an escalated vulnerability to environmental challenges. ABBREVIATIONS: BW, body weight; CR, calorie restriction; EC, epicatechin-treated; ECM, extracellular matrix; EGCG, epigallocatechin gallate; FPKM, fragments per kilobase of transcript per 106 mapped reads; H&E, hematoxylin and eosin; PPAR, peroxisome proliferator–activated receptor; NAD, nicotinate and nicotinamide; OC, old control; PAS, periodic acid–Schiff; SkM, skeletal muscle; UPLC-MS/MS, ultra-high-performance liquid chromatography–tandem mass spectroscopy; USDA, U.S Department of Agriculture; YC, young control Resveratrol, a well-known phytochemical, has been shown to improve health and extend life span by mimicking CR in obese mice induced by feeding of a highfat diet [5] but not in mice fed a standard chow diet [6] These findings indicate that the resveratrol effect is mediated by favorable modulation of the increased vulnerability to the physiologic and metabolic alterations of major organs and tissues induced by feeding of a high-fat diet or obesity but not via directly targeting antiaging molecules within healthy aging processes. Identifying safe, bioactive compounds with robust antiaging effects in rodents and humans remains an elusive goal
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