西湖大学最新Nature Aging论文：线粒体tRNA突变会在肾脏中积累，导致严重肾病

Core Viewpoint - The study highlights the age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys, which is linked to mitochondrial kidney diseases, emphasizing the importance of monitoring kidney function in mitochondrial disease patients, especially the elderly [3][4]. Group 1: Research Findings - The research utilized a mitochondrial base editor, DdCBE, to create pathogenic mitochondrial tRNA point mutation mouse models, revealing that these mutations accumulate with age in the kidneys, leading to severe renal defects that mimic human mitochondrial kidney disease [3][6]. - The study identified unique heterogeneity dynamics in different kidney cell types, where podocytes exhibited positive selection for mutated mtDNA, while renal tubular epithelial cells showed neutral drift of mutations during aging [6][7]. - A comprehensive analysis combining mtscATAC-seq, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (Stereo-seq) determined molecular changes in high mutation-defect cells, including enhanced AP-1 family transcription factor activity, renal tubular epithelial cell proliferation, and immune activation, which promote disease progression [7]. Group 2: Implications for Clinical Practice - The findings underscore the necessity for monitoring kidney function in elderly patients with mitochondrial diseases, establishing a reliable preclinical model to facilitate the development of therapeutic strategies [4].