The potential use of physical resilience to predict healthy aging.
The potential use of physical resilience to predict healthy aging.
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DOI：
10.1080/20010001.2017.1403844
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ladiges W
中科院分区：
文献类型：
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作者：
Schorr A;Carter C;Ladiges W
身体弹性是有机体对严重破坏正常生理稳态的压力源做出反应的能力。根据定义，弹性随着年龄的增长而降低，而脆弱性（定义为组织功能的下降）则随着年龄的增长而增加。因此，对复原力的评估可能是一种信息丰富的早期范式，可以预测健康衰老与衰弱（衡量晚年功能障碍）的比较。实验室小鼠的恢复力参数尚未明确定义，并且不存在单一的标准化压力测试。由于衰老涉及多种遗传途径，因此需要测量涉及多个组织、器官和活动的综合反应，以揭示整体的弹性状态，这表明一系列压力测试，而不是单一的包罗万象的压力测试，将提供最丰富的信息。本综述描述了三种简单、可靠且廉价的压力源，可用作确定弹性水平的面板。短暂的冷水浸泡允许恢复正常体温的时间，作为对低温恢复能力的指标，即恢复到正常体温的速度越快，恢复能力越强。睡眠剥夺（SD）会损害老年小鼠的远程记忆，并对葡萄糖代谢产生不利影响。环磷酰胺（CYP）靶向白细胞，尤其是骨髓细胞，导致中性粒细胞减少症，并以年龄依赖性方式导致中性粒细胞增多症反弹。因此，强烈的中性粒细胞反应表明有恢复能力。总之，弹性有望成为生物年龄（即特定器官或组织衰老速度）的特别有用的衡量标准。寒冷、SD 和 CYP 这三种压力源适用于人类医学和衰老，因为它们代表临床相关的压力条件，并以年龄依赖性方式产生影响。因此，它们对于小鼠弹性测试来说是一种有吸引力的扰动，以衡量针对基本衰老过程的干预措施的有效性。
Physical resilience is the ability of an organism to respond to stressors that acutely disrupt normal physiological homeostasis. By definition, resilience decreases with increasing age, while frailty, defined as a decline in tissue function, increases with increasing age. Assessment of resilience could therefore be an informative early paradigm to predict healthy aging compared to frailty, which measures late life dysfunction. Parameters for resilience in the laboratory mouse are not yet well defined, and no single standardized stress test exists. Since aging involves multiple genetic pathways, integrative responses involving multiple tissues, organs, and activities need to be measured to reveal the overall resilience status, suggesting a battery of stress tests, rather than a single all-encompassing one, would be most informative. Three simple, reliable, and inexpensive stressors are described in this review that could be used as a panel to determine levels of resilience. Brief cold water immersion allows a recovery time to normothermia as an indicator of resilience to hypothermia, i.e. the quicker the return to normal body temperature, the more robust the resilience. Sleep deprivation (SD) impairs remote memory in aged mice, and has detrimental effects on glucose metabolism. Cyclophosphamide (CYP) targets white blood cells, especially myeloid cells resulting in neutropenia with a rebound neutrophilia in an age-dependent manner. Thus a strong neutrophilic response indicates resilience. In conclusion, resilience promises to be an especially useful measurement of biological age, i.e. how fast a particular organ or tissue ages. The three stressors, cold, SD, and CYP, are applicable to human medicine and aging because they represent clinically relevant stress conditions that have effects in an age-dependent manner. They are thus an attractive perturbation for resilience testing in mice to measure the effectiveness of interventions that target basic aging processes.