最近对端粒（染色体端部的保护性末端）和线粒体之间的一个功能联系的揭示，提出这样一个可能性：二者都可能涉及与衰老相关的过程。现在，对来自小鼠心脏和肝脏组织的造血干细胞的转录组（全部RNA内容）所做的一项分析，表明存在一个“端粒- p53-PGC”轴线，这个轴线将端粒功能丧失与器官功能降低联系了起来，而且也可能与跟年龄相关的病变联系了起来。在端粒丧失功能的小鼠中，p53-调控的细胞生长停滞被激活，接着它又抑制PGC-1α 和 PGC-1β（代谢过程和线粒体过程的主要调控因子）。这会导致线粒体质量减少、线粒体功能丧失和ATP生成量减少、糖生成受损、心肌功能受损和活性氧增加。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09787
Telomere dysfunction induces metabolic and mitochondrial compromise
Ergün Sahin,1, 2 Simona Colla,1, 2, 10 Marc Liesa,3, 10 Javid Moslehi,2, 4 Florian L. Müller,1, 2 Mira Guo,5 Marcus Cooper,6 Darrell Kotton,3 Attila J. Fabian,7 Carl Walkey,8 Richard S. Maser,1, 2 Giovanni Tonon,1, 2 Friedrich Foerster,1, 2 Robert Xiong,1 Y. Alan Wang,1 Sachet A. Shukla,1 Mariela Jaskelioff,1, 2 Eric S. Martin,1, 2 Timothy P. Heffernan,1 Alexei Protopopov,1 Elena Ivanova,1 John E. Mahoney,1 Maria Kost-Alimova,1 Samuel R. Perry,1 Roderick Bronson,9
Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.
