Santos-Otte Paula, Leysen Hanne, van Gastel Jaana, Hendrickx Jhana O, Martin Bronwen, Maudsley Stuart
Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, 01062 Dresden, Germany.
Receptor Biology Lab, University of Antwerp, 2610 Antwerp, Belgium.
Comput Struct Biotechnol J. 2019 Aug 23;17:1265-1277. doi: 10.1016/j.csbj.2019.08.005. eCollection 2019.
Aging is a complex biological process that is inevitable for nearly all organisms. Aging is the strongest risk factor for development of multiple neurodegenerative disorders, cancer and cardiovascular disorders. Age-related disease conditions are mainly caused by the progressive degradation of the integrity of communication systems within and between organs. This is in part mediated by, ) decreased efficiency of receptor signaling systems and ) an increasing inability to cope with stress leading to apoptosis and cellular senescence. Cellular senescence is a natural process during embryonic development, more recently it has been shown to be also involved in the development of aging disorders and is now considered one of the major hallmarks of aging. G-protein-coupled receptors (GPCRs) comprise a superfamily of integral membrane receptors that are responsible for cell signaling events involved in nearly every physiological process. Recent advances in the molecular understanding of GPCR signaling complexity have expanded their therapeutic capacity tremendously. Emerging data now suggests the involvement of GPCRs and their associated proteins in the development of cellular senescence. With the proven efficacy of therapeutic GPCR targeting, it is reasonable to now consider GPCRs as potential platforms to control cellular senescence and the consequently, age-related disorders.
衰老 是一个复杂的生物学过程,几乎对所有生物体来说都是不可避免的。衰老是多种神经退行性疾病、癌症和心血管疾病发生的最强风险因素。与年龄相关的疾病状况主要是由器官内部和器官之间通讯系统完整性的渐进性退化引起的。这部分是由以下因素介导的:(1)受体信号系统效率降低;(2)应对压力导致细胞凋亡和细胞衰老的能力日益下降。细胞衰老是胚胎发育过程中的一个自然过程,最近研究表明它也与衰老相关疾病的发生有关,现在被认为是衰老的主要标志之一。G蛋白偶联受体(GPCRs)构成了一个整合膜受体超家族,负责几乎所有生理过程中涉及的细胞信号事件。对GPCR信号复杂性的分子理解方面的最新进展极大地扩展了它们的治疗能力。新出现的数据表明GPCRs及其相关蛋白参与了细胞衰老的发生。鉴于治疗性靶向GPCR的已证实疗效,现在有理由将GPCRs视为控制细胞衰老以及由此产生的与年龄相关疾病的潜在平台。