Department of Physics, University of Toronto, Toronto, Canada.
Blavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, United States.
Elife. 2022 Nov 21;11:e77632. doi: 10.7554/eLife.77632.
As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage. We assess differences in robustness and resilience using changes in damage rates and repair rates of binary health attributes. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening aging health - as assessed by the frailty index (FI). A decline in robustness, however, has a greater effect than a decline in resilience on the accelerated increase of the FI with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales toward organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice. We have also explored the correlations with household wealth for humans. We find that these interventions and factors affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners.
随着生物体的衰老,其健康状况取决于损伤和修复过程之间的平衡。测量这些过程需要纵向数据。我们从老鼠和人类的二元健康属性的重复观察中提取损伤和修复转换率,以探索稳健性和弹性,它们分别代表抵抗或从损伤中恢复。我们使用二元健康属性的损伤率和修复率的变化来评估稳健性和弹性的差异。我们发现老鼠和人类的稳健性和弹性随着年龄的增长而呈保守性下降,这意味着两者都导致了衰老健康状况的恶化——正如脆弱指数(FI)所评估的那样。然而,与弹性下降相比,稳健性下降对 FI 随年龄加速增加的影响更大,与存活率降低的关联更大。我们还发现,缺陷在从最短的测量尺度到生物体寿命尺度的广泛时间尺度上被损坏和修复。我们探讨了已经显示出改善健康的系统干预措施的影响,包括老鼠的血管紧张素转换酶抑制剂依那普利和自愿运动。我们还探索了人类与家庭财富的相关性。我们发现这些干预措施和因素以年龄和性别依赖的方式影响损伤和修复率,从而影响稳健性和弹性。