Ghachem Ahmed, Dufour Frédérik, Fülöp Tamas, Gaudreau Pierrette, Cohen Alan A
Department of Medicine, Research Center on Aging, University of Sherbrooke, Sherbrooke, Québec, Canada.
Department of Family Medicine, PRIMUS Research Group, University of Sherbrooke, Sherbrooke, Québec, Canada.
Gerontology. 2021;67(6):660-673. doi: 10.1159/000514169. Epub 2021 Mar 29.
Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL).
The objectives of this study were (1) to assess the magnitude and rate of changes in physiologi-cal dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality).
We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids.
As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL.
Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.
诸如生理失调（体内平衡能力的逐渐丧失）等生物过程中与年龄相关的变化在老年人中差异很大，并且可能影响晚年的健康状况。这些差异可能至少部分与性别和身体活动水平（PAL）等内在和外在因素的影响有关。
本研究的目的是（1）根据PAL评估男性和女性生理失调的变化幅度和速率，以及（2）确定性别和PAL是否/如何介导生理失调对健康结局（衰弱和死亡率）的明显影响。
我们使用了魁北克NuAge队列研究中1754名社区居住老年人（年龄=74.4±4.2岁；女性=52.4%）的数据。生理失调是根据重新组合为5个系统的31种生物标志物的马氏距离计算得出的：氧运输、肝/肾功能、白细胞生成、微量营养素和脂质。
正如预期的那样，平均生理失调随年龄显著增加，而PAL下降。对于相同年龄和PAL，男性在3个系统中总体上表现出较高水平的生理失调：氧运输、肝/肾功能和白细胞生成。男性在肝/肾和白细胞生成系统中还表现出更快的总体生理失调。总体而言，高PAL与较低水平和较慢的生理失调变化速率相关。最后，虽然死亡率和衰弱风险随生理失调显著增加，但没有证据表明性别和PAL在这些影响上存在差异。
我们的结果表明，性别和PAL对生理失调水平和变化速率都有显著影响。此外，虽然较高的PAL与较低水平和较慢的生理失调变化速率相关，但没有证据表明PAL会减弱生理失调对生命末期后续健康下降的影响。仍有大量工作有待开展，以了解可改变的行为如何影响男性和女性生理失调、衰弱和死亡率之间的关系。
