Golubev A G
N.N.Petrov National Medical Research Center of Oncology, 68, Leningradskaya srt., Pesochnyi, St. Petersburg, 197758, Russian Federation; e-mail:
Adv Gerontol. 2018;31(4):458-472.
The chemical properties of compounds involved in metabolic processes, even the core ones, such as glycolysis and Krebs cycle, are not limited to what is realized via enzymatic reactions, because the properties include the abilities to form spontaneousely covalent bonds with other compounds, incuding those incorporated in macromolecules. The effects of the gene that codes for an enzyme, which catalizes the formation of a metabolite, which features such extra properties, may be regarded as antagonistically pleiotropic. The effects that are realized via the product of the reaction catalysed by the enzyme coded by a gene are required for current viability. The effects that are mediated by the spontaneous formation of covalent bonds between the same product and slowly renewable macromolecules will be increasingly deleterious with increasing time of their accumulation provided by the positive effects. Thus, the antagonistically pleiotripic effects are not late-acting, as it is commonly believed, but rather they are cumulative. Since these effects are inseparable from metabolism, they may be labeled "parametabolic". The driving force produced by these effects is sufficient for aging to take place in any system that exists due to metabolic processes therein and proliferate due to information stored by components featuring much slower turnover compared with that of metabolites. Thus, we age because of the chemical properties of our constituents and do it so as it is determined by these properies realized within conditions of our bodies. Aging is neither a direct product of evolution (such as a program that determines the span of life), nor a byproduct (a delayed payment for current advantages). Aging results from limitations that the immanent physicochemical properties of metabolites impose on the capabilities and outcomes of evolution by natural selection, and this is what distinguishes aging from the tear and wear of inanimate objects.
参与代谢过程的化合物的化学性质,即使是核心过程(如糖酵解和三羧酸循环)中的化合物,也不限于通过酶促反应实现的性质,因为这些性质包括与其他化合物自发形成共价键的能力,包括那些并入大分子中的化合物。编码一种酶的基因的作用,该酶催化具有这种额外性质的代谢物的形成,可能被视为拮抗性多效性。通过由基因编码的酶催化的反应产物实现的作用是当前生存所必需的。由同一产物与缓慢可再生的大分子之间自发形成共价键介导的作用,随着其由积极作用提供的积累时间增加,将越来越有害。因此,拮抗性多效性作用并非如通常所认为的那样是后期起作用的,而是累积性的。由于这些作用与代谢不可分割,它们可被标记为“副代谢”。这些作用产生的驱动力足以使任何因其中的代谢过程而存在并因与代谢物相比周转慢得多的成分所储存的信息而增殖的系统发生衰老。因此,我们衰老的原因是我们身体成分的化学性质,并按照这些性质在我们身体条件下实现的方式进行衰老。衰老既不是进化的直接产物(如决定寿命跨度的程序),也不是副产品(对当前优势的延迟代价)。衰老是由代谢物固有的物理化学性质对自然选择进化的能力和结果所施加的限制导致的,这就是衰老与无生命物体的磨损的区别所在。