Osawa Yusuke, Semba Richard D, Fantoni Giovanna, Candia Julián, Biancotto Angélique, Tanaka Toshiko, Bandinelli Stefania, Ferrucci Luigi
Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Aging Cell. 2020 Apr;19(4):e13132. doi: 10.1111/acel.13132. Epub 2020 Mar 10.
Mobility disability is a powerful indicator of poor health in older adults. The biological and pathophysiological mechanism underlying the development of mobility disability remains unknown. This study conducted a data-driven discovery phase investigation to identify plasma proteins that predict the incidence of mobility disability in community-dwelling older adults without mobility disability at baseline.
We investigated 660 women and men, aged 71.9 ± 6.0 (60-94) years, who participated in the Invecchiare in Chianti, "Aging in the Chianti Area" study and completed the 400-m walk at fast pace (400-m walk) at enrollment. Median follow-up time was 8.57 [interquartile, 3.20-9.08] years. SOMAscan technology was used to measure 1,301 plasma proteins at enrollment. The incident of mobility disability was defined as inability to complete the 400-m walk. Protein-specific Cox proportional hazard model was adjusted for sex, age, and other important covariates.
Plasma levels of 75 proteins predicted mobility disability (p < .05). Significant proteins were enriched for the KEGG "PI3K-Akt signaling," "phagosomes," and "cytokine-cytokine receptor interaction" pathways. After multiple comparison adjustment, plasma cathepsin S (CTSS; hazard ratio [HR] 1.33, 95% CI: 1.17, 1.51, q = 0.007), growth/differentiation factor 15 (GDF15; HR: 1.45, 95% CI: 1.23, 1.72, q = 0.007), and thrombospondin-2 (THBS2; HR: 1.44, 95% CI: 1.22, 1.69, q = 0.007) remained significantly associated with high risk of losing mobility.
CTSS, GDF15, and THBS2 are novel blood biomarkers associated with new mobility disability in community-dwelling individuals. Overall, our analysis suggests that cellular senescence and inflammation should be targeted for prevention of mobility disability.
行动不便在老年人健康状况不佳方面是一个有力指标。行动不便发展背后的生物学和病理生理机制仍不清楚。本研究进行了一个数据驱动的探索阶段调查，以识别能够预测社区居住的、基线时无行动不便的老年人发生行动不便的血浆蛋白。
我们调查了660名年龄在71.9±6.0（60 - 94）岁的男性和女性，他们参与了基安蒂地区的衰老研究（Invecchiare in Chianti，“Aging in the Chianti Area”），并在入组时完成了400米快速步行（400米步行测试）。中位随访时间为8.57[四分位间距，3.20 - 9.08]年。在入组时使用SOMAscan技术测量1301种血浆蛋白。行动不便的发生定义为无法完成400米步行。蛋白质特异性Cox比例风险模型针对性别、年龄和其他重要协变量进行了调整。
75种蛋白质的血浆水平可预测行动不便（p < 0.05）。显著的蛋白质在KEGG“PI3K - Akt信号传导”、“吞噬体”和“细胞因子 - 细胞因子受体相互作用”途径中富集。经过多重比较调整后，血浆组织蛋白酶S（CTSS；风险比[HR] 1.33，95%置信区间：1.17，1.51，q = 0.007）、生长/分化因子15（GDF15；HR：1.45，95%置信区间：1.23，1.72，q = 0.007）和血小板反应蛋白 - 2（THBS2；HR：1.44，95%置信区间：1.22，1.69，q = 0.007）仍然与失去行动能力的高风险显著相关。
CTSS、GDF15和THBS2是与社区居住个体新发行动不便相关的新型血液生物标志物。总体而言，我们的分析表明，细胞衰老和炎症应作为预防行动不便的靶点。
