Stolzenbach Victor, Woods Dori C, Tilly Jonathan L
Laboratory of Aging and Infertility Research, Department of Biology, Northeastern University, Boston, MA, United States.
Front Cell Dev Biol. 2022 Aug 23;10:942652. doi: 10.3389/fcell.2022.942652. eCollection 2022.
The concept of natural selection, or "survival of the fittest", refers to an evolutionary process in nature whereby traits emerge in individuals of a population through random gene alterations that enable those individuals to better adapt to changing environmental conditions. This genetic variance allows certain members of the population to gain an advantage over others in the same population to survive and reproduce in greater numbers under new environmental pressures, with the perpetuation of those advantageous traits in future progeny. Here we present that the behavior of adult stem cells in a tissue over time can, in many respects, be viewed in the same manner as evolution, with each stem cell clone being representative of an individual within a population. As stem cells divide or are subjected to cumulative oxidative damage over the lifespan of the organism, random genetic alterations are introduced into each clone that create variance in the population. These changes may occur in parallel to, or in response to, aging-associated changes in microenvironmental cues perceived by the stem cell population. While many of these alterations will be neutral or silent in terms of affecting cell function, a small fraction of these changes will enable certain clones to respond differently to shifts in microenvironmental conditions that arise with advancing age. In some cases, the same advantageous genetic changes that support survival and expansion of certain clones over others in the population (viz. non-neutral competition) could be detrimental to the downstream function of the differentiated stem cell descendants. In the context of the germline, such a situation would be devastating to successful propagation of the species across generations. However, even within a single generation, the "evolution" of stem cell lineages in the body over time can manifest into aging-related organ dysfunction and failure, as well as lead to chronic inflammation, hyperplasia, and cancer. Increased research efforts to evaluate stem cells within a population as individual entities will improve our understanding of how organisms age and how certain diseases develop, which in turn may open new opportunities for clinical detection and management of diverse pathologies.
自然选择的概念，即“适者生存”，指的是自然界中的一种进化过程，通过种群个体中随机的基因改变，某些特征得以出现，使这些个体能够更好地适应不断变化的环境条件。这种基因变异使种群中的某些成员比其他成员更具优势，从而在新的环境压力下能够存活并大量繁殖，这些有利特征也会在后代中延续下去。在这里，我们提出，随着时间的推移，组织中成年干细胞的行为在许多方面可以用与进化相同的方式来看待，每个干细胞克隆都代表种群中的一个个体。在生物体的生命周期中，随着干细胞分裂或受到累积的氧化损伤，随机的基因改变被引入每个克隆中，从而在种群中产生变异。这些变化可能与干细胞群体所感知的与衰老相关的微环境线索变化同时发生，或者是对这些变化的反应。虽然这些改变中的许多在影响细胞功能方面是中性的或沉默的，但其中一小部分变化将使某些克隆能够对随着年龄增长而出现的微环境条件变化做出不同反应。在某些情况下，支持种群中某些克隆比其他克隆存活和扩张的相同有利基因变化（即非中性竞争）可能对分化后的干细胞后代的下游功能有害。在种系的背景下，这种情况对物种跨代的成功繁殖将是毁灭性的。然而，即使在单一代内，体内干细胞谱系随时间的“进化”也可能表现为与衰老相关的器官功能障碍和衰竭，以及导致慢性炎症、增生和癌症。加大对种群内干细胞个体的评估研究力度，将增进我们对生物体衰老以及某些疾病如何发生发展的理解，进而可能为多种病理状况的临床检测和管理带来新的机遇。
