Exercise improves aging-induced cardiac dysfunction and prolongs lifespan via Hmgcr

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-08-14 DOI:10.1016/j.lfs.2025.123897

Zhengwen Yu , Qiufang Li , Meng Ding , Xu Ping , Wenzhi Gu , Qin Yi , Jin Dai , Rui Tian , Zhihao Pan , Lan Zheng

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引用次数: 0

Abstract

Since the incidence of cardiovascular disease increases dramatically with age, it is crucial to understand the molecular mechanisms of heart damage in aging and how to reduce the damage caused by aging to the heart. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR) is the rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of HMG-CoA to mevalonate (MVA). Hmgcr not only affects cholesterol synthesis during the development process, but also regulates primordial germ cell migration and affects heart development. We investigated the expression and function of Hmgcr during cardiac development and aging. Changes during cardiac development may affect its entire life cycle. We used the Drosophila aging model to explore the expression changes of Hmgcr in the aging heart. The results showed that aging led to a significant decrease in the expression level of Hmgcr in cardiac tissue, accompanied by impaired cardiac function. Specific upregulation of cardiac Hmgcr expression can significantly improve aging-related cardiac dysfunction and extend lifespan. Interestingly, exercise can improve cardiac function and extend lifespan by upregulating Hmgcr expression levels in the aging heart. This finding provides a new theoretical basis for exercise to improve aging heart function and lifespan.

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运动通过Hmgcr改善老年性心功能障碍，延长寿命。

由于心血管疾病的发病率随着年龄的增长而急剧增加，因此了解衰老过程中心脏损伤的分子机制以及如何减少衰老对心脏的损伤是至关重要的。3-羟基-3-甲基戊二酰辅酶A （HMG-CoA）还原酶（HMGCR）是胆固醇生物合成的限速步骤，并催化HMG-CoA转化为甲羟戊二酸（MVA）。Hmgcr不仅影响发育过程中胆固醇的合成，还调节原始生殖细胞的迁移，影响心脏发育。我们研究了Hmgcr在心脏发育和衰老过程中的表达和功能。心脏发育过程中的变化可能影响其整个生命周期。我们采用果蝇衰老模型，探讨衰老心脏中Hmgcr的表达变化。结果显示，衰老导致心肌组织Hmgcr表达水平显著降低，并伴有心功能受损。特异性上调心脏Hmgcr表达可显著改善衰老相关性心功能障碍，延长寿命。有趣的是，运动可以通过上调衰老心脏中Hmgcr的表达水平来改善心脏功能并延长寿命。这一发现为运动改善衰老心脏功能和延长寿命提供了新的理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.