最近對(duì)端粒（染色體端部的保護(hù)性末端）和線粒體之間的一個(gè)功能聯(lián)系的揭示，提出這樣一個(gè)可能性：二者都可能涉及與衰老相關(guān)的過(guò)程?，F(xiàn)在,，對(duì)來(lái)自小鼠心臟和肝臟組織的造血干細(xì)胞的轉(zhuǎn)錄組（全部RNA內(nèi)容）所做的一項(xiàng)分析，表明存在一個(gè)“端粒- p53-PGC”軸線,，這個(gè)軸線將端粒功能喪失與器官功能降低聯(lián)系了起來(lái),，而且也可能與跟年齡相關(guān)的病變聯(lián)系了起來(lái)。在端粒喪失功能的小鼠中,，p53-調(diào)控的細(xì)胞生長(zhǎng)停滯被激活,，接著它又抑制PGC-1α 和 PGC-1β（代謝過(guò)程和線粒體過(guò)程的主要調(diào)控因子）。這會(huì)導(dǎo)致線粒體質(zhì)量減少,、線粒體功能喪失和ATP生成量減少,、糖生成受損、心肌功能受損和活性氧增加,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
