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年龄和饮食限制可调节雄性小鼠股四头肌中线粒体的质量。

Age and dietary restriction modulate mitochondrial quality in quadriceps femoris muscle of male mice.

机构信息

Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei, 10672, Taiwan.

出版信息

Biogerontology. 2024 Jun;25(3):447-459. doi: 10.1007/s10522-023-10086-3. Epub 2024 Jan 6.

Abstract

Dietary restriction (DR) is a potential intervention for ameliorating ageing-related damages. Mitochondrial quality control is the key mechanism for regulating cellular functions in skeletal muscle. This study aimed to explore the effect of age and DR on the homeostasis of mitochondrial quality control in skeletal muscle. To study the effect of age on mitochondrial homeostasis, young (3 months old) male C57BL/6J mice were fed ad libitum (AL) until 7 (Young), 14 (Middle), and 19 months (Aged) of age. For the DR intervention, 60% of AL intake was given to the mice at 3 months of age until they reached 19 months of age (16 months). The quadriceps femoris muscle was collected for further analysis. Significant changes in the skeletal muscle were noticed during the transition between middle age and the elderly stages. An accumulation of collagen was observed in the muscle after middle age. Compared with the Middle muscle, Aged muscle displayed a greater expression of VDAC, and lower expressions of mitochondrial dynamic proteins and OXPHOS proteins. The DR intervention attenuated collagen content and elongated the sarcomere length in the skeletal muscle during ageing. In addition, DR adjusted the abnormalities in mitochondrial morphology in the Aged muscle. DR downregulated VDAC expression, but upregulated OPA1 and DRP1 expressions. Taken together, greater pathological changes were noticed in the skeletal muscle during ageing, especially in the transition between middle age and the elderly, whereas early-onset DR attenuated the muscular ageing via normalising partial functions of mitochondria.

摘要

饮食限制(DR)是改善与衰老相关损伤的一种潜在干预措施。线粒体质量控制是调节骨骼肌细胞功能的关键机制。本研究旨在探讨年龄和 DR 对骨骼肌中线粒体质量控制的动态平衡的影响。为了研究年龄对线粒体动态平衡的影响,将年轻(3 个月大)雄性 C57BL/6J 小鼠进行自由喂养(AL),直到 7(年轻)、14(中年)和 19 个月(老年)。对于 DR 干预,在 3 个月大时,将 60%的 AL 摄入量给予小鼠,直到它们达到 19 个月大(16 个月)。收集股四头肌进行进一步分析。从中年到老年阶段的过渡过程中,骨骼肌发生了显著变化。中年后肌肉中观察到胶原蛋白的积累。与中年肌肉相比,老年肌肉的 VDAC 表达增加,线粒体动态蛋白和 OXPHOS 蛋白的表达降低。DR 干预减弱了衰老过程中骨骼肌中的胶原蛋白含量,并延长了肌节长度。此外,DR 调整了老年肌肉中线粒体形态的异常。DR 下调了 VDAC 的表达,但上调了 OPA1 和 DRP1 的表达。总之,在衰老过程中骨骼肌发生了更大的病理变化,尤其是从中年到老年的过渡阶段,而早期 DR 通过使线粒体的部分功能正常化来减轻肌肉衰老。

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