Ying W
School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Med Hypotheses. 1997 Feb;48(2):143-8. doi: 10.1016/s0306-9877(97)90281-4.
It is becoming increasingly apparent that free-radical damage, mitochondrial defects, glycation/Maillard reaction and calcium dyshomeostasis play crucial roles in cellular and organism senescence. Based on the evidence indicating close relationships among these four aging-promoting factors, a unifying hypothesis of senescence-the deleterious network hypothesis of aging-is proposed: In living organisms, both endogenous and exogenous detrimental factors produce age-dependent accumulation of triggering of a deleterious network, which is constructed on the basis of the interactions among oxidative impairments, mitochondrial defects, calcium mismetabolism and glycation/Maillard reaction. The age-related triggering of the network leads to numerous senescent alterations. It appears that this novel theory has synthesized multiple hypotheses of aging, and is capable of providing consistent explanations to a larger number of senescent changes than any previous hypotheses. Based on the new theory of senescence, it is proposed that the approaches which can inhibit the initiation of the four key age-promoting factors should be applied combinatively to slow down the aging process and to prevent and treat age-associated illnesses.
自由基损伤、线粒体缺陷、糖基化/美拉德反应以及钙稳态失调在细胞和机体衰老过程中发挥着关键作用，这一点正变得越来越明显。基于表明这四种促衰老因素之间存在密切关系的证据，提出了一种统一的衰老假说——衰老的有害网络假说：在生物体内，内源性和外源性有害因素都会导致有害网络触发的年龄依赖性积累，该网络是基于氧化损伤、线粒体缺陷、钙代谢异常以及糖基化/美拉德反应之间的相互作用构建而成。与年龄相关的网络触发会导致众多衰老改变。看来这一新颖理论综合了多种衰老假说，并且能够比以往任何假说对更多的衰老变化提供一致的解释。基于新的衰老理论，有人提出应联合应用能够抑制这四种关键促衰老因素启动的方法，以减缓衰老进程，并预防和治疗与年龄相关的疾病。
