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早期饮食限制可维持衰老过程中心左室的线粒体健康、自噬和内质网功能。

Early-onset dietary restriction maintains mitochondrial health, autophagy and ER function in the left ventricle during aging.

机构信息

Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.

General Research Service Center & Department of Animal Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.

出版信息

J Nutr Biochem. 2022 Mar;101:108944. doi: 10.1016/j.jnutbio.2022.108944. Epub 2022 Jan 10.

DOI:10.1016/j.jnutbio.2022.108944
PMID:35017002
Abstract

Dietary restriction (DR) exerts healthy benefits, including heart functions. However, the cardioprotective role of DR is till controversial among researchers due to the variation of DR conditions. The present study focuses on the protective effect of early-onset DR on cardiac injury using mitochondrial structure and expression of protein associated with mitochondrial homeostasis, autophagy and endoplasmic reticulum (ER) function as measures. 2-month-old mice were fed with a breeding diet ad libitum (AL) or DR (60% of AL) for 3 (Young) or 20 (Aged) months. Body weight increased with aging, whereas DR treatment kept body weight consistent. DR mice exhibited a higher relative heart weight than AL mice. DR mice displayed lower plasma glucose levels, compared with AL groups. Furthermore, Aged-AL, but not Aged-DR mice, had increased collagen content and morphological distortions in the left ventricle (LV). Aged-DR mice had a higher ATP and lower TBARS in the LV than Aged-AL mice. Mitochondrial morphology was detected by electron microscopy; Aged-AL mice had increased abnormal morphology of mitochondria. Treatment with DR reduced abnormal mitochondrial accumulation. Aging elevated the protein expressions of mitochondrial functions and ER-induced apoptosis. Aging downregulated autophagy related proteins and chaperones in the heart. Dietary restriction reversed those protein expressions. The present study demonstrated a beneficial effect of early onset DR on cardiac aging. The age-dependent mitochondrial dysfunction and protein quality control dysregulation was significantly reversed by long-term DR, demonstrating a concordance with the beneficial effect in the heart.

摘要

饮食限制(DR)发挥健康益处,包括心脏功能。然而,由于 DR 条件的变化,DR 对心脏的保护作用在研究人员中仍存在争议。本研究以线粒体结构和与线粒体稳态、自噬和内质网(ER)功能相关的蛋白质表达为指标,研究早期 DR 对心脏损伤的保护作用。2 月龄小鼠自由进食(AL)或 DR(AL 的 60%)3(幼年期)或 20(老年期)个月。体重随年龄增长而增加,而 DR 处理保持体重一致。DR 小鼠的相对心脏重量高于 AL 小鼠。DR 小鼠的血浆葡萄糖水平低于 AL 组。此外,与 Aged-DR 小鼠相比,Aged-AL 小鼠左心室(LV)胶原含量增加,形态扭曲。与 Aged-AL 小鼠相比,Aged-DR 小鼠 LV 中的 ATP 更高,TBARS 更低。通过电子显微镜检测线粒体形态;Aged-AL 小鼠的线粒体形态异常增加。DR 治疗减少了异常线粒体的积累。衰老增加了与线粒体功能和 ER 诱导细胞凋亡相关的蛋白质表达。衰老下调了心脏中的自噬相关蛋白和伴侣蛋白。DR 逆转了这些蛋白质的表达。本研究表明早期 DR 对心脏衰老有有益的影响。长期 DR 显著逆转了与年龄相关的线粒体功能障碍和蛋白质质量控制失调,与心脏的有益作用一致。

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