Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167470. doi: 10.1016/j.bbadis.2024.167470. Epub 2024 Aug 15.
Aging disrupts brain function, leading to cognitive decline and neurodegenerative diseases. Senescent astrocytes, a hallmark of aging, contribute to this process through unknown mechanisms. This study investigates how senescence impacts astrocytic mitochondrial dynamics, which are critical for brain health. Our research, conducted using aged mouse brains, represents the first evidence of morphologically damaged mitochondria in astrocytes, along with functional alterations in mitochondrial respiration. In vitro experiments revealed that senescent astrocytes exhibit an increase in mitochondrial fragmentation and impaired mitophagy. Concurrently, there was an upregulation of mitochondrial biogenesis, indicating a compensatory response to mitochondrial damage. Importantly, these senescent astrocytes were more susceptible to mitochondrial stress, a vulnerability reversed by rapamycin treatment. These findings suggest a potential link between senescence, impaired mitochondrial quality control, and increased susceptibility to mitochondrial stress in astrocytes. Overall, our study highlights the importance of addressing mitochondrial dysfunction and senescence-related changes in astrocytes as a promising approach for developing therapies to counter age-related neurodegeneration and improve brain health.
衰老是大脑功能紊乱的主要原因，会导致认知能力下降和神经退行性疾病。衰老星形胶质细胞是衰老的标志之一，但其通过未知机制促进这一过程。本研究调查了衰老如何影响星形胶质细胞的线粒体动力学，这对大脑健康至关重要。我们的研究使用衰老的老鼠大脑，首次证明了星形胶质细胞中线粒体形态受损，以及线粒体呼吸功能改变。体外实验表明衰老的星形胶质细胞中线粒体碎片化增加，自噬受损。同时，线粒体生物发生增加，表明这是对线粒体损伤的一种代偿反应。重要的是，这些衰老的星形胶质细胞对线粒体应激更敏感，雷帕霉素治疗可逆转这种脆弱性。这些发现表明衰老、受损的线粒体质量控制以及星形胶质细胞中线粒体应激易感性增加之间可能存在联系。总的来说，我们的研究强调了解决星形胶质细胞中线粒体功能障碍和衰老相关变化的重要性，这是开发治疗方法以对抗与年龄相关的神经退行性变和改善大脑健康的有前途的方法。
