Subject(s)
Insurance Coverage/statistics & numerical data , Patient Discharge/statistics & numerical data , Spinal Cord Stimulation/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Patient Discharge/economics , Retrospective Studies , Spinal Cord Stimulation/economics , Young AdultABSTRACT
There is evidence implicating oxidative stress (OS) as the cause of the deleterious effects of aging. In this study, we evaluated the capacity of the flavanol (-)-epicatechin (Epi) to reduce aging-induced OS and restore mitochondrial biogenesis, as well as, structural and functional endpoints in aged mice. Senile (S; 26-month-old) C57BL/6 male mice were randomly assigned to receive either water (vehicle) or 1mg/kg of Epi via oral gavage (twice daily) for 15 days. Young (Y; 6-month-old) mice were used as controls. In S brain, kidney, heart, and skeletal muscle (compared with Y animals) an increase in OS was observed as evidenced by increased protein-free carbonyls and decreased reduced glutathione levels as well as sirtuin 3, superoxide dismutase 2, catalase, thioredoxin and glutathione peroxidase protein levels. Well-recognized factors (eg, sirtuin 1) that regulate mitochondrial biogenesis and mitochondrial structure- and/or function-related endpoints (eg, mitofilin and citrate synthase) protein levels were also reduced in S organs. In contrast, the aging biomarker senescence-associated ß-galactosidase was increased in S compared with Y animals, and Epi administration reduced levels towards those observed in Y animals. Altogether, these data suggest that Epi is capable of shifting the biology of S mice towards that of Y animals.
Subject(s)
Aging/drug effects , Aging/physiology , Catechin/pharmacology , Organelle Biogenesis , Oxidative Stress/drug effects , Oxidative Stress/physiology , Age Factors , Animals , Brain/metabolism , Brain/pathology , Citrate (si)-Synthase/metabolism , Kidney/metabolism , Kidney/pathology , Male , Mice , Mice, Inbred C57BL , Mitochondrial Proteins/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Myocardium/metabolism , Myocardium/pathology , Oxidoreductases/metabolism , beta-Galactosidase/metabolismABSTRACT
Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (-)-epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (-)-Epicatechin may thus hold promise as treatment for sarcopenia. We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated ß-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (-)-Epicatechin decreases myostatin and ß-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and ß-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (-)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, and the consumption of modest amounts of the flavanol (-)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia.
