Department of Biological, Chemical and Physical Sciences, Roosevelt University, Chicago, IL 60605, USA.
Cancer Res Treat. 2009 Dec;41(4):187-95. doi: 10.4143/crt.2009.41.4.187. Epub 2009 Dec 31.
Cellular senescence is a mechanism that induces an irreversible growth arrest in all somatic cells. Senescent cells are metabolically active but lack the capacity to replicate. Evolutionary theories suggest that cellular senescence is related to the organismal decline occurring in aging organisms. Also, such theories describe senescence as an antagonistically pleiotropic process that can have beneficial or detrimental effect on the organism. Cellular senescence is believed to be involved in the cellular changes observed as aging progresses. Accumulation of senescent cells appears to occur widely as the organism ages. Furthermore, senescence is a key element of the tumor suppressor pathways. Therefore, it is part of the natural barrier against the uncontrolled proliferation observed in cellular development of malignancies in multicellular organisms. Activation of the senescence process guarantees a limited number of cellular replications. The genetic network led by p53 is responsible for activation of senescence in response to DNA damage and genomic instability that could lead to cancer. A better comprehension of the genetic networks that control the cell cycle and induce senescence is important to analyze the association of senescence to longevity and diseases related to aging. For these reasons, experimental research both in vitro and in vivo aims to develop anticancer therapies based on senescence activation. The last decade of research on role and function of senescence in aging and cancer are discussed in this paper.
细胞衰老(Cellular senescence)是一种诱导所有体细胞不可逆生长停滞的机制。衰老细胞代谢活跃,但缺乏复制能力。进化理论表明,细胞衰老与衰老生物体内发生的机体衰退有关。此外,这些理论将衰老描述为一种拮抗多效性过程,对生物体可能有有益或有害的影响。细胞衰老被认为与衰老过程中观察到的细胞变化有关。随着生物体的衰老,衰老细胞的积累似乎广泛发生。此外,衰老还是肿瘤抑制途径的关键要素。因此,它是多细胞生物中恶性肿瘤细胞不受控制增殖的天然屏障的一部分。衰老过程的激活保证了细胞复制的有限数量。p53 领导的遗传网络负责激活衰老,以应对可能导致癌症的 DNA 损伤和基因组不稳定性。更好地理解控制细胞周期并诱导衰老的遗传网络对于分析衰老与长寿和与衰老相关疾病的关联非常重要。出于这些原因,体外和体内的实验研究旨在基于衰老的激活来开发抗癌疗法。本文讨论了过去十年关于衰老和癌症中衰老作用和功能的研究。