A GlyNAC-supplemented diet for 12 weeks modestly improved cardiac diastolic function in 21-month-old male mice but not females, who surprisingly showed a decline in exercise performance.
Does a diet supplemented with glycine and N-acetyl cysteine (GlyNAC) improve cardiac function and exercise performance in 21-month-old mice?
GlyNAC supplementation improves cardiac diastolic function in aged male mice but not females, highlighting significant sex differences in response to antioxidant interventions in the aging heart.
Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a subunit of the mitochondrial respiratory chain complex), and higher enzymatic activity for CPT1b and CrAT, 2 carnitine acyltransferases that are critical to cardiomyocyte metabolism. Although no quantifiable change of collagen turnover was detected, hearts from GlyNAC-fed old males exhibited a slight but significant enrichment in Fmod, a protein that can inhibit collagen fibril formation, possibly reducing extracellular matrix stiffness and thus improving diastolic function. Cardiac diastolic function was modestly improved in males but not females, and surprisingly GlyNAC-fed female mice showed a decline in exercise performance. In summary, our work supports the concept that aged male and female hearts are phenotypically different. These basic differences may affect the response to pharmacological and diet interventions, including antioxidants.
Angelini et al. (Mon,) conducted a other in Cardiac aging. GlyNAC (glycine and N-acetyl cysteine) supplemented diet vs. Control diet was evaluated on Heart function and exercise performance. A GlyNAC-supplemented diet for 12 weeks modestly improved cardiac diastolic function in 21-month-old male mice but not females, who surprisingly showed a decline in exercise performance.