ProSoma, LLC, Clearwater, FL 33756, USA.
Cells. 2022 Mar 7;11(5):917. doi: 10.3390/cells11050917.
There is consensus among biogerontologists that aging occurs either as the result of a purposeful genome-based, evolved program or due to spontaneous, randomly occurring, maladaptive events. Neither concept has yet identified a specific mechanism to explain aging's emergence and acceleration during mid-life and beyond. Presented herein is a novel, unifying mechanism with empirical evidence that describes how aging becomes continuous with development. It assumes that aging emerges from deterioration of a regulatory process that directs morphogenesis and morphostasis. The regulatory system consists of a genome-wide "backbone" within which its specific genes are differentially expressed by the local epigenetic landscapes of cells and tissues within which they reside, thereby explaining its holistic nature. Morphostasis evolved in humans to ensure the nurturing of dependent offspring during the first decade of young adulthood when peak parental vitality prevails in the absence of aging. The strict redundancy of each morphostasis regulatory cycle requires sensitive dependence upon initial conditions to avoid initiating deterministic chaos behavior. However, when natural selection declines as midlife approaches, persistent, progressive, and specific DNA damage and misrepair changes the initial conditions of the regulatory process, thereby compromising morphostasis regulatory redundancy, instigating chaos, initiating senescence, and accelerating aging thereafter.
生物老年学家一致认为，衰老要么是基于有目的的基因组、进化而来的程序的结果，要么是由于自发的、随机发生的、适应不良的事件。这两个概念都没有确定一个特定的机制来解释衰老在中年及其后如何出现和加速。本文提出了一种新颖的、统一的机制，并提供了经验证据，描述了衰老如何与发育连续发生。它假设衰老是由指导形态发生和形态稳定的调节过程的恶化引起的。调节系统由一个全基因组的“主干”组成，其中特定的基因通过其所在的细胞和组织的局部表观遗传景观进行差异表达，从而解释了其整体性。形态稳定在人类中进化，是为了在年轻成年的头十年中，当父母的生命力达到顶峰而没有衰老时，确保对依赖的后代的养育。每个形态稳定调节周期的严格冗余性需要对初始条件敏感依赖，以避免引发确定性混沌行为。然而，当接近中年时，自然选择下降，持续的、渐进的、特定的 DNA 损伤和错误修复会改变调节过程的初始条件，从而破坏形态稳定调节的冗余性，引发混沌，启动衰老，此后加速衰老。
