Reed Rebecca, Miwa Satomi
Biosciences Institute, Faculty of Medical Sciences, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
Subcell Biochem. 2023;102:139-173. doi: 10.1007/978-3-031-21410-3_7.
Cellular senescence has become a subject of great interest within the ageing research field over the last 60 years, from the first observation in vitro by Leonard Hayflick and Paul Moorhead in 1961, to novel findings of phenotypic sub-types and senescence-like phenotype in post-mitotic cells. It has essential roles in wound healing, tumour suppression and the very first stages of human development, while causing widespread damage and dysfunction with age leading to a raft of age-related diseases. This chapter discusses these roles and their interlinking pathways, and how the observed accumulation of senescent cells with age has initiated a whole new field of ageing research, covering pathologies in the heart, liver, kidneys, muscles, brain and bone. This chapter will also examine how senescent cell accumulation presents in these different tissues, along with their roles in disease development. Finally, there is much focus on developing treatments for senescent cell accumulation in advanced age as a method of alleviating age-related disease. We will discuss here the various senolytic and senostatic treatment approaches and their successes and limitations, and the innovative new strategies being developed to address the differing effects of cellular senescence in ageing and disease.
在过去60年里,细胞衰老已成为衰老研究领域中备受关注的课题,从1961年伦纳德·海弗利克(Leonard Hayflick)和保罗·莫尔黑德(Paul Moorhead)在体外的首次观察,到有丝分裂后细胞中表型亚型和衰老样表型的新发现。它在伤口愈合、肿瘤抑制和人类发育的最初阶段起着至关重要的作用,同时随着年龄增长会造成广泛的损伤和功能障碍,导致一系列与年龄相关的疾病。本章将讨论这些作用及其相互关联的途径,以及随着年龄增长观察到的衰老细胞积累如何开启了一个全新的衰老研究领域,涵盖心脏、肝脏、肾脏、肌肉、大脑和骨骼中的病理学。本章还将研究衰老细胞在这些不同组织中的积累情况,以及它们在疾病发展中的作用。最后,人们非常关注开发针对老年期衰老细胞积累的治疗方法,作为减轻与年龄相关疾病的一种手段。我们将在此讨论各种衰老细胞溶解和衰老细胞静止治疗方法及其成功之处和局限性,以及为应对细胞衰老在衰老和疾病中的不同影响而正在开发的创新新策略。