Liang Ting, Bernal Belinda, Qi Wenbo, Ikeno Yuji, Salmon Adam B, Kwok Daisy, Michalek Joel, Zhou Mai, Bai Yidong
Department of Cell Systems and Anatomy.
Barshop Institute for Longevity and Aging Studies.
Organelle. 2025;1(2). doi: 10.61747/0ifp.202408002. Epub 2024 Nov 8.
Naked mole-rats (NMR, ) are the longest-lived rodent species, with a maximum life span of more than 30 years. These long-lived mammals exhibit delayed aging phenotypes and resistance to age-related pathologies including neurodegeneration. Multiple regulatory pathways have been proposed for the anti-aging mechanisms in NMR including enhanced mitochondrial function and suppressed oxidative stress. In this study, we investigated the assembly of the electron transfer chain (ETC) which constitutes the structural base for the regulation of both oxidative phosphorylation and the production of reactive oxygen species (ROS), in brains from young and old NMR and C57BL/6 mice. While ETC assembly declined with aging in C57BL/6 mice, we found that NMR display a robust respiratory chain assembly at older ages in both males and females. Among them, individual complex IV and supercomplexes containing complex I and III or complex III and IV showed the most pronounced differences between two species. Our results indicate that a preserved robust assembly of ETC during aging contributes to enhanced mitochondrial oxidative phosphorylation and suppressed oxidative stress, which may contribute to the longevity and resistance to age-related pathologies in NMR.
裸鼹鼠是寿命最长的啮齿动物物种，最长寿命超过30年。这些长寿哺乳动物表现出衰老延迟的表型，并对包括神经退行性变在内的与年龄相关的病理变化具有抵抗力。关于裸鼹鼠的抗衰老机制，已经提出了多种调控途径，包括增强线粒体功能和抑制氧化应激。在本研究中，我们调查了年轻和老年裸鼹鼠及C57BL/6小鼠大脑中电子传递链（ETC）的组装情况，电子传递链构成了氧化磷酸化和活性氧（ROS）产生调控的结构基础。虽然C57BL/6小鼠的ETC组装随年龄增长而下降，但我们发现裸鼹鼠在老年时，无论雄性还是雌性，都表现出强大的呼吸链组装。其中，单个复合物IV以及包含复合物I和III或复合物III和IV的超复合物在两个物种之间表现出最明显的差异。我们的结果表明，衰老过程中ETC的强大组装得以保留，有助于增强线粒体氧化磷酸化并抑制氧化应激，这可能有助于裸鼹鼠的长寿以及对与年龄相关病理变化的抵抗力。
