Chigira M, Watanabe H
Department of Orthopedic Surgery, Gunma University School of Medicine, Japan.
Med Hypotheses. 1993 Oct;41(4):384-9. doi: 10.1016/0306-9877(93)90090-d.
So-called 'limited life span' of diploid cells does not depend on their unresponsiveness to growth factors from the data obtained by complete protein-free culture of tumor cells. Limited proliferation (called limited life span) of diploid cells is one of the 'ad-hoc' negative regulatory mechanisms in animals, and can not be differentiated from other inhibitory mechanisms called 'tumor suppression' and 'terminal differentiation'. Metabolic imbalance induced by proliferation-dependent time-bomb mechanisms including infidelity of DNA repair is suggested to explain limited proliferation of cells. After maturation, autonomic progression of negative regulators in cells is induced by no prohibition of terminal differentiation, since organisms prepare no programs to stop development and differentiation. It is an attractive hypothesis that a proliferation-dependent time-bomb has been developed to control organogenesis for maturation and to determine body size. It is true that limited proliferation of cells can not explain longevity of individuals, although the so-called longevity genes play roles in ageing. Teleologically, longevity of individuals has been developed to produce genetic heterogeneity according to the selfish gene theory. This inter- and intra-species genetic heterogeneity increases the probability of selfish gene replication in germ cell line. After maturation and reproduction of DNA in germ cell line, individuals as vehicles for the DNA can be discarded by the 'selfish' genes.
从肿瘤细胞完全无蛋白培养所获数据来看,二倍体细胞所谓的“有限寿命”并不取决于它们对生长因子无反应。二倍体细胞的有限增殖(称为有限寿命)是动物体内一种“特设”的负调控机制,且无法与其他被称为“肿瘤抑制”和“终末分化”的抑制机制区分开来。包括DNA修复错误在内的依赖增殖的定时炸弹机制所诱导的代谢失衡,被认为可以解释细胞的有限增殖。成熟后,由于生物体没有准备阻止发育和分化的程序,不禁止终末分化会诱导细胞内负调控因子的自主进展。有一种颇具吸引力的假说认为,为了控制器官成熟发育和确定体型,已经形成了一种依赖增殖的定时炸弹机制。诚然,细胞的有限增殖无法解释个体的长寿,尽管所谓的长寿基因在衰老过程中发挥作用。从目的论角度来看,根据自私基因理论,个体的长寿是为了产生遗传异质性。这种种间和种内的遗传异质性增加了自私基因在生殖细胞系中复制的概率。在生殖细胞系中DNA成熟并复制后,作为DNA载体的个体可能会被“自私”基因抛弃。