Balasubramanyam M, Adaikalakoteswari A, Monickaraj S Finny, Mohan V
Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, Chennai, India.
Indian J Med Res. 2007 Mar;125(3):441-50.
Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during ageing. Over the past decade, emerging evidence has shown that the telomeres are essential regulators of cellular life span and chromosome integrity in a dynamic fashion. By inducing genomic instability, replicative senescence and apoptosis, shortening of telomeres is thought to contribute to organismal ageing. While the aetiology of cardiovascular diseases and diabetes represent a complex interaction between various risk factors overlaid on different genetic backgrounds, the conventional risk factors often did not explain the inter-individual variability related to predisposition of disease states. This underscores the need for biological indicators of ageing in evaluating the aetiology of several age-related disorders, and recent studies indicate that telomere length could qualify as an ideal marker of biological ageing. Short telomeres have been detected in senescent endothelial cells and vascular smooth muscle cells from human atherosclerotic plaque as well as in myocardial tissue from patients with end-stage heart failure and cardiac hypertrophy. In addition, telomere shortening has been demonstrated in WBCs from patients with coronary heart disease, premature myocardial infarction, hypertension and diabetes mellitus. In this review, we discuss the telomere hypothesis of ageing as well as human studies that address the role of telomeres in cardiovascular, diabetes and other cardio-metabolic pathologies.
端粒是位于真核染色体末端的特殊DNA-蛋白质结构，在大多数体细胞衰老过程中其长度会逐渐缩短。在过去十年中，新出现的证据表明，端粒以动态方式对细胞寿命和染色体完整性起着至关重要的调节作用。端粒缩短被认为会通过诱导基因组不稳定、复制性衰老和细胞凋亡，从而导致机体衰老。虽然心血管疾病和糖尿病的病因代表了在不同遗传背景下各种风险因素之间的复杂相互作用，但传统风险因素往往无法解释与疾病易感性相关的个体间差异。这凸显了在评估几种与年龄相关疾病的病因时，需要生物学衰老指标，最近的研究表明端粒长度可能是生物学衰老的理想标志物。在人类动脉粥样硬化斑块的衰老内皮细胞和血管平滑肌细胞以及终末期心力衰竭和心肌肥大患者的心肌组织中，均检测到了短端粒。此外，在冠心病、早发性心肌梗死、高血压和糖尿病患者的白细胞中也证实了端粒缩短。在这篇综述中，我们讨论了衰老的端粒假说以及探讨端粒在心血管、糖尿病和其他心脏代谢疾病中作用的人体研究。
