Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.
EMBO J. 2011 May 17;30(13):2520-31. doi: 10.1038/emboj.2011.162.
Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, senescent decline and ageing is broadly influenced by genetic and extrinsic factors. Numerous gene mutations and treatments have been shown to extend the lifespan of diverse organisms ranging from the unicellular Saccharomyces cerevisiae to primates. It is becoming increasingly apparent that most such interventions ultimately interface with cellular stress response mechanisms, suggesting that longevity is intimately related to the ability of the organism to effectively cope with both intrinsic and extrinsic stress. Here, we survey the molecular mechanisms that link ageing to main stress response pathways, and mediate age-related changes in the effectiveness of the response to stress. We also discuss how each pathway contributes to modulate the ageing process. A better understanding of the dynamics and reciprocal interplay between stress responses and ageing is critical for the development of novel therapeutic strategies that exploit endogenous stress combat pathways against age-associated pathologies.
衰老是由生物分子中对细胞正常功能至关重要的损伤的不可避免和随机积累所驱动的。尽管这个过程从根本上是偶然的且不可控的，但衰老和衰老的下降在很大程度上受到遗传和外在因素的影响。大量的基因突变和治疗方法已经被证明可以延长从单细胞酿酒酵母到灵长类动物等多种生物的寿命。越来越明显的是，大多数此类干预措施最终都与细胞应激反应机制相互作用，这表明长寿与生物体有效应对内在和外在应激的能力密切相关。在这里，我们调查了将衰老与主要应激反应途径联系起来的分子机制，并介导了与应激反应有效性相关的年龄变化。我们还讨论了每个途径如何有助于调节衰老过程。更好地了解应激反应和衰老之间的动态和相互作用对于开发利用内源性应激对抗与年龄相关的病理的新型治疗策略至关重要。
