Salnikov Lev
AntiCA Biomed San Diego, CA 92111, USA.
Biochemistry (Mosc). 2022 Dec;87(12):1498-1503. doi: 10.1134/S0006297922120070.
The review presents a brief outline of the current state of the main theoretical approaches to the aging problem. The works of authors, supporting the theory of "accumulation of errors" and theories stating the presence of a hypothetical "aging program" in all multicellular organisms are reviewed. The role of apoptosis and its connection with phenoptosis, as well as the theory of "hyperfunction" are analyzed. Our own approach to this problem is presented, in which aging is explained by the redistribution of limited resources between the two main aims of the organism: its self-sufficiency, based on the function of the housekeeping genes (HG) group, and functional specialization, provided by the integrative genes (IntG) group. Agreeing with the inseparable connection between aging and the ontogenesis program, the main role in the aging mechanisms is assigned to the redistribution of resources from the HG self-sufficiency genes to the IntGs necessary for the operation of all specialized functions of the organism as a whole. The growing imbalance between HGs and IntGs with age, suggests that switching of cellular resources in favor of IntGs is a side effect of ontogenesis program implementation and the main reason for aging, inherent in the nature of genome functioning under conditions of highly integrated multicellularity. The hypothesis of functional subdivision of the genome also points to the leading role of slow-dividing and postmitotic cells, as the most sensitive to reduction of repair levels, for triggering and realization of the aging process.
这篇综述简要概述了衰老问题的主要理论方法的现状。回顾了支持“错误积累”理论以及表明所有多细胞生物中存在假设的“衰老程序”的理论的作者的著作。分析了细胞凋亡的作用及其与自然凋亡的联系,以及“功能亢进”理论。介绍了我们自己对这个问题的方法,其中衰老被解释为有限资源在生物体的两个主要目标之间的重新分配:基于管家基因组(HG)功能的自我维持,以及由整合基因组(IntG)提供的功能特化。认同衰老与个体发育程序之间不可分割的联系,衰老机制中的主要作用被归因于资源从HG自我维持基因重新分配到整个生物体所有专门功能运作所需的IntG。随着年龄增长,HG和IntG之间日益失衡,这表明细胞资源向IntG的转换是个体发育程序实施的副作用,也是衰老的主要原因,这是在高度整合的多细胞条件下基因组功能本质所固有的。基因组功能细分的假设也指出,缓慢分裂和有丝分裂后细胞作为对修复水平降低最敏感的细胞,在触发和实现衰老过程中起主导作用。