Faragher Richard G A, Sheerin Angela N, Ostler Elizabeth L
School of Pharmacy and Biomolecular Science, University of Brighton, Brighton, BN2 4GJ, UK.
Expert Rev Mol Med. 2009 Sep 7;11:e27. doi: 10.1017/S1462399409001197.
Ageing is a progressive failure of defence and repair processes that produces physiological frailty (the loss of organ reserve with age), loss of homeostasis and eventual death. Over the past ten years exceptional progress has been made in understanding both why the ageing process happens and the mechanisms that are responsible for it. The study of natural mutants that accelerate some, but not all, of the features of the human ageing process has now progressed to a degree that drug trials are either taking place or can be envisaged. Simultaneously, a series of mutations have been identified in different species that confer extended healthy life, indicating that the ageing process is much more malleable than might have been expected and that single interventions have the potential to delay the onset of multiple age-associated conditions. Data generated using these organisms have led to the formulation of a powerful new hypothesis, the 'green theory' of ageing. This proposes that a finite capacity to carry out broad-spectrum detoxification and recycling is the primary mechanistic limit on organismal lifespan. This is turn suggests important new experimental approaches and potential interventions designed to increase healthy lifespan.
衰老指的是防御和修复过程的渐进性衰退,这会导致生理脆弱(随着年龄增长器官储备功能丧失)、体内平衡失调并最终导致死亡。在过去十年里,在理解衰老过程发生的原因及其背后机制方面取得了显著进展。对加速人类衰老过程某些(而非全部)特征的自然突变体的研究如今已发展到一定程度,药物试验正在进行或可以设想。与此同时,在不同物种中已鉴定出一系列能延长健康寿命的突变,这表明衰老过程比预期更具可塑性,单一干预措施有可能延缓多种与年龄相关病症的发作。利用这些生物体产生的数据催生了一个强有力的新假说,即衰老的“绿色理论”。该理论提出,进行广谱解毒和循环利用的有限能力是生物体寿命的主要机制限制。这进而暗示了旨在延长健康寿命的重要新实验方法和潜在干预措施。