Department of Cell Biology and Histology, Faculty of Medicine, University of the Basque Country UPV/EHU, Leioa, 48940 Vizcaya, Spain.
Department of Dermatology, Ophthalmology and Otorhinolaryngology, Basurto University Hospital, Faculty of Medicine, University of the Basque Country UPV/EHU, Gurtubay s/n, 48013 Bilbao, Spain.
Ageing Res Rev. 2015 Sep;23(Pt B):125-38. doi: 10.1016/j.arr.2015.03.004. Epub 2015 Apr 4.
Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing.
人类衰老与身体在多个层面的生理功能逐渐下降有关，它是许多疾病的关键风险因素，包括癌症。衰老过程与广泛的细胞衰老密切相关，其特征是增殖能力的不可逆转丧失和与端粒磨损、DNA 损伤积累以及线粒体和代谢功能受损相关的功能改变。肿瘤和衰老细胞可能是对相同刺激的反应产生的，其中细胞衰老或转化将构成同一退化过程的两种相反结果。本文旨在综述细胞衰老、衰老和癌症之间的生物分子关系的现有知识。重要的是，在细胞衰老和肿瘤发生过程中发现许多改变的细胞信号通路都通过共同的表观遗传机制进行调节，因此它们具有潜在的可逆转性。microRNAs 作为连接衰老和癌症的关键因素而备受关注。这些小分子 RNA 从癌症的未来临床治疗的角度来看引起了极大的兴趣，因为在动物模型中已经获得了成功的实验结果。针对癌症的 micro-RNA 疗法已经在临床试验阶段进行测试。这些发现对于老年人的癌症治疗具有潜在的重要性，尽管需要进一步的基于研究的知识才能将其转化为与衰老相关的癌症有效分子疗法。
