Macedo Joana Catarina, Vaz Sara, Logarinho Elsa
Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
Adv Exp Med Biol. 2017;1002:153-188. doi: 10.1007/978-3-319-57127-0_7.
Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.
衰老 是一个生物学过程，其特征在于生理功能的逐渐衰退，而生理功能衰退是已知的慢性疾病和健康状况下降的主要风险因素。衰老与非整倍体（染色体数目异常）之间的联系日益显现，尽管与年龄相关的非整倍体背后的分子机制在很大程度上仍不清楚。近年来，已经确定了几个控制衰老速度的遗传途径和生化过程，并将其作为衰老的标志提出。导致细胞损伤积累的主要标志包括基因组不稳定、端粒磨损、表观遗传改变和蛋白质稳态丧失（López-Otín等人，《细胞》153:1194 - 1217，2013年）。在这里，我们回顾了这些衰老标志与细胞分裂过程中染色体分离保真度丧失之间的引发性联系，这可能支持过去几十年来所观察到的衰老与非整倍体之间的相关性。其次，我们回顾了非整倍体对细胞生理学的系统性影响，并强调这些影响如何包括一些衰老的主要标志。基于这些证据，我们提出衰老与非整倍体之间存在相互因果关系，并建议调节有丝分裂保真度作为改善健康寿命的一种潜在手段。
