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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #427276
Research Project: Regulatory Aspects of Nutritional Metabolism

Location: Children's Nutrition Research Center

Title: Sex differences in response to diet enriched with glutathione precursors in the aging heart

Author
item ANGELINI, AUDE - Houston Methodist Research Institute
item GARCIA MARQUEZ, GRECIA - Houston Methodist Research Institute
item MALOVANNAYA, ANNA - Baylor College Of Medicine
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)
item SALTZMAN, ALEXANDER - Baylor College Of Medicine
item JAIN, ANTRIX - Baylor College Of Medicine
item TRIAL, JOANN - Houston Methodist Research Institute
item TAFFET, GEORGE - Houston Methodist Research Institute
item CIESLIK, KATARZYNA - Houston Methodist Research Institute

Submitted to: Gerontological Society of America
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/2024
Publication Date: 11/4/2024
Citation: Angelini, A., Garcia Marquez, G., Malovannaya, A., Fiorotto, M.L., Saltzman, A., Jain, A., Trial, J., Taffet, G.E., Cieslik, K.A. 2024. Sex differences in response to diet enriched with glutathione precursors in the aging heart. Gerontological Society of America. 80(2). Article glae258. https://doi.org/10.1093/gerona/glae258.
DOI: https://doi.org/10.1093/gerona/glae258

Interpretive Summary: As we age, the heart tends to develop problems like poor metabolism, inflammation, and tissue stiffening. This study tested whether boosting natural antioxidants in older mice could help improve heart health. Aged male and female mice were fed a special diet for 3 months supplemented with the ingredients (GlyNAC) the body need to make the antioxidant, glutathione. Male mice improved their heart metabolism and exercise capacity, while female mice did not benefit and even had reduced exercise capacity. The results suggest that male and female hearts age differently and may respond differently to treatments. This highlights the importance of considering sex differences in developing therapies for aging hearts.

Technical 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.