Publication Date
1-16-2025
Journal
The Journals of Gerontology: Series A
DOI
10.1093/gerona/glae258
PMID
39492659
PMCID
PMC11788829
PubMedCentral® Posted Date
11-4-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Female, Male, Mice, Aging, Glutathione, Acetylcysteine, Mice, Inbred C57BL, Sex Factors, Oxidative Stress, Glycine, Heart, Antioxidants, Myocardium, Dietary Supplements, Diet, Biology of aging, Cardiovascular disease, Extracellular matrix, Mitochondria, Sex differences
Abstract
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.
Graphical Abstract
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Community Health and Preventive Medicine Commons, Dietetics and Clinical Nutrition Commons, Neurosciences Commons, Nutrition Commons, Pediatrics Commons
