Diastolic dysfunction in the aged population is multifactorial. Common features of the aging heart are dysregulated metabolism, elevated oxidative stress, inflammation and fibrosis, where each of these conditions can linked together and further promote the altered phenotype. It becomes increasingly apparent that aged male and female hearts are phenotypically different and these basic differences dictate their responses to treatments such as a response to antioxidants. We used Glycine and N-Acetyl-Cysteine (GlyNAC, precursors of glutathione)- supplemented diet to monitor its effect on cardiac function and exercise performance. We found that this pharmacological intervention was beneficial for male but not female aged mice and the small but significant changes were observed not only on cardiac functions but also on molecular levels where fatty acid metabolism was improved and cardiac matrix stiffness was reduced.