Aging cellular networks: Chaperones as major participants

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• 关键词：Molecular chaperones ; Heat shock proteins ; Stress proteins ; Chaperone overload ; Networks ; Protein– ; protein interaction networks ; Signaling networks ; Gene transcription regulatory networks ; Stochastic resonance
• 刊名：Experimental Gerontology
• 出版年：2007
• 出版时间：January-February 2007
• 年：2007
• 卷：42
• 期：1-2
• 页码：113-119
• 全文大小：237 K

文摘

We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key “networkers”, which sequester and repair damaged proteins. In order to link the network approach and chaperones with the aging process, we first summarize the properties of aging networks suggesting a “weak link theory of aging”. This theory suggests that age-related random damage primarily affects the overwhelming majority of the low affinity, transient interactions (weak links) in cellular networks leading to increased noise, destabilization and diversity. These processes may be further amplified by age-specific network remodelling and by the sequestration of weakly linked cellular proteins to protein aggregates of aging cells. Chaperones are weakly linked hubs (i.e., network elements with a large number of connections) and inter-modular bridge elements of protein–protein interaction, signalling and mitochondrial networks. As aging proceeds, the increased overload of damaged proteins is an especially important element contributing to cellular disintegration and destabilization. Additionally, chaperone overload may contribute to the increase of “noise” in aging cells, which leads to an increased stochastic resonance resulting in a deficient discrimination between signals and noise. Chaperone- and other multi-target therapies, which restore the missing weak links in aging cellular networks, may emerge as important anti-aging interventions.