衰老细胞作为衰老相关疾病治疗靶点的价值-SCI医学论文-基础医学论文-医学论文.docxVIP

衰老细胞作为衰老相关疾病治疗靶点的价值-SCI医学论文-基础医学论文-医学论文 ——文章均为WORD文档，下载后可直接编辑使用亦可打印—— 　　摘 要：　衰老是一个新兴的重要研究领域，随着领域相关知识的积累和技术的进步，人们逐渐意识到衰老本身可以被针对性地干预，实现延长寿命并且延缓衰老相关疾病的发生发展，具有重要的科学和现实意义.在引起个体衰老的众多因素中，衰老细胞的积累被认为是导致器官衰老发生退行性变，最终引起衰老相关疾病的重要原因. 近年来，多项研究表明清除体内衰老细胞可以延缓多种衰老相关疾病的发生，直接证明了衰老细胞是导致衰老相关疾病的重要原因之一，为治疗衰老相关疾病提供了新靶点. 细胞衰老是由于损伤积累 发了细胞周期抑制通路的激活，细胞永久地退出细胞增殖周期. 衰老细胞会发生细胞形态、转录谱、蛋白质稳态、表观遗传以及代谢等系列特征的改变，同时衰老细胞对凋亡发生抵抗从而在体内多器官组织积累. 衰老细胞会激活炎症因子分泌通路，导致组织局部非感染性炎症微环境，进而导致器官退行性变及多种衰老相关疾病的发生发展. 因此针对衰老细胞对凋亡抵抗的特性，多个研究小组通过筛选小分子化合物库，发现某些化合物能够选择性清除衰老细胞，这些小分子化合物被称为senolytics，意为衰老细胞杀伤性化合物. 衰老细胞杀伤性化合物在多种衰老相关疾病动物模型中能够延缓疾病的发展并延长哺乳动物寿命. 因此，靶向杀伤衰老细胞对多种衰老相关疾病的治疗从而提高健康寿命具有重要的临床应用前景. 除靶向杀伤衰老细胞策略以外，干细胞移植、基因编辑、异体共生等策略在抗衰老研究发展中也具有重要意义，具有启发性. 本文通过汇总近期衰老细胞清除领域的重要进展和多种抗衰老策略，将细胞衰老研究发展史做简要梳理，就细胞衰老与衰老相关疾病的关系作一综述，重点讨论衰老细胞在多种衰老相关疾病中作为治疗靶点的应用潜力，并就其局限性和进一步的研究方向进行探讨. 　　关键词：　细胞衰老; 抗衰老; 老龄化疾病; 药物靶点; 　　Abstract：　Aging is an emerging and important research area. With the accumulation of knowledge in related fields and the advancement of technology, people gradually realized that aging itself can be intervened and it is of great scientific and practical significance to delay aging, especially delaying the occurrence and development of age-related diseases. Among the many factors that cause individual aging, the accumulation of senescent cells is considered to be an important reason that leads to organ aging and degeneration, and finally causes the age-related diseases. In recent years, a number of studies have shown that removing senescent cells in vivo can delay the occurrence of multiple age-related diseases, which directly proves that senescent cells are one of the important causes of age-related diseases, providing a new target for the treatment of age-related diseases. Cellular senescence is generally considered due to the activation of cell cycle inhibition pathway induced by accumulation of damages, and the cells permanently exit the proliferation cycle. Senescent cells undergo changes in cell morphology, transcriptional