Hanson M A, Cooper C, Aihie Sayer A, Eendebak R J, Clough G F, Beard J R
Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK.
NIHR Nutrition Biomedical Research Centre, University Hospital Southampton, UK.
J Physiol. 2016 Apr 15;594(8):2147-60. doi: 10.1113/JP270579. Epub 2016 Feb 4.
We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health.
我们研究了从发育角度看待人类衰老的机制基础及其更广泛的影响。以往的衰老模型主要关注其遗传基础,或累积损伤的有害影响,但也引发了一些问题,比如衰老本身是否可被视为适应性的,或者它是否是其他适应性过程的结果,例如在繁殖前阶段的维持和修复过程是否会与后期功能衰退相互权衡。一个生命历程模型将衰老置于身体系统达到峰值能力的背景下,始于早期发育阶段,此时可塑性允许一系列环境刺激引发结构和功能的变化,随后是一个衰退期,衰退速度取决于所达到的峰值以及后期生活条件。衰老速度中的这种路径依赖性可能为其调节提供新的见解。以肌肉骨骼和心血管功能为重点,我们讨论了这个模型以及可能的潜在机制,包括内皮功能、氧化应激、干细胞和营养因素,如维生素D状态。发育可塑性过程中诱导的表观遗传变化以及免疫功能可能为衰老的生命历程模型提供一个共同的机制过程。生命历程轨迹在高资源和低资源环境中有所不同。对衰老生命历程模型中发育成分的新见解可能会促成后期慢性病风险生物标志物的设计以及促进健康衰老的新干预措施,这对公共卫生具有重要意义。