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, two 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 (ECM) 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.

中文翻译：

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衰老心脏对富含谷胱甘肽前体的饮食的反应的性别差异


心脏衰老的常见特征是新陈代谢失调、炎症和纤维化。氧化应激升高是心脏衰老的另一个标志，它会加剧这些情况。我们假设通过增加天然抗氧化剂水平（谷胱甘肽），我们将改善心脏功能。21 个月大的小鼠饲喂补充甘氨酸和 N-乙酰半胱氨酸 （GlyNAC） （谷胱甘肽前体）或对照饮食 12 周。纵向监测心脏功能，并在研究结束时确定运动表现。我们发现 GlyNAC 饮食对老年雄性小鼠有益，但对老年雌性小鼠无益处，导致 Ndufb8 表达增加（线粒体呼吸链复合物的一个亚基），以及 CPT1b 和 CrAT 的酶活性更高，这两种肉碱酰基转移酶对心肌细胞代谢至关重要。虽然没有检测到胶原蛋白周转的可量化变化，但 GlyNAC 喂养的老年男性的心脏表现出轻微但显着的 Fmod 富集，Fmod 是一种可以抑制胶原蛋白原纤维形成的蛋白质，可能降低细胞外基质 （ECM） 刚度，从而改善舒张功能。雄性心脏舒张功能适度改善，但雌性未得到改善，令人惊讶的是，GlyNAC 喂养的雌性小鼠运动表现下降。总之，我们的工作支持老年男性和女性心脏表型不同的概念。这些基本差异可能会影响对药物和饮食干预（包括抗氧化剂）的反应。