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衰老机制作为适应的“负面”:一种网络方法。

Aging mechanism as the "down side" of adaptation: a network approach.

作者信息

Borup Mia T, Trusina Ala, Andersson Anna M C

机构信息

Center for Models of Life, The Niels Bohr Institute, Copenhagen, Denmark.

出版信息

J Theor Biol. 2008 Jan 7;250(1):66-74. doi: 10.1016/j.jtbi.2007.09.016. Epub 2007 Sep 19.

Abstract

Many diverse hypotheses on aging are in play. All from "aging genes" over decreasing telomere length to increased level of gene mutations has been suggested to determine an organism's lifespan, but no unifying theory exists. As part of a growing interest toward more integrative approaches in the field we propose a simplistic model based on the "use-it-or-lose-it" concept: we hypothesize that biological aging is a systemic property and the down side of adaptation in complex biological networks at various levels of organization: from brain over the immune system to specialized tissues or organs. The simple dynamical model undergoes three phases during its lifetime: (1) general plasticity (childhood), (2) optimization/adaptation to given conditions (youth and adolescence) and (3) steady state associated with high rigidity (aging). Furthermore, our model mimics recent data on the dynamics of the immune system during aging and, although simplistic, thus captures essential characteristics of the aging process. Finally, we discuss the abstract model in relation to current knowledge on aging and propose experimental setups for testing some of the theoretical predictions.

摘要

关于衰老存在许多不同的假说。从“衰老基因”到端粒长度缩短,再到基因突变水平增加,所有这些都被认为决定了生物体的寿命,但不存在统一的理论。作为该领域对更综合方法日益增长的兴趣的一部分,我们基于“用进废退”的概念提出了一个简单的模型:我们假设生物衰老具有系统性,是复杂生物网络在从大脑到免疫系统再到特定组织或器官等各个组织层次上适应的负面结果。这个简单的动力学模型在其生命周期中经历三个阶段:(1)一般可塑性(童年),(2)对给定条件的优化/适应(青年和青春期),以及(3)与高刚性相关的稳态(衰老)。此外,我们的模型模拟了衰老过程中免疫系统动力学的最新数据,尽管很简单,但捕捉到了衰老过程的基本特征。最后,我们结合当前关于衰老的知识讨论了这个抽象模型,并提出了用于测试一些理论预测的实验设置。

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