Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), 31000, Toulouse, France.
Maintain Aging Research team, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Inserm, Université Paul Sabatier, Toulouse, France.
Geroscience. 2023 Dec;45(6):3409-3418. doi: 10.1007/s11357-023-00906-2. Epub 2023 Aug 24.
Intrinsic capacity (IC), the composite of physical and mental capacities, declines with age at different rates and patterns between individuals. We aimed to investigate the association between longitudinal IC trajectories and plasma biomarkers of two hallmarks of aging-chronic inflammation and mitochondrial dysfunction-in older adults. From the Multidomain Alzheimer Preventive Trial (MAPT), we included 1271 community-dwelling older people (mean [SD] age = 76.0 [4.3] years) with IC data over four years. Group-based multi-trajectory modeling was performed to identify clusters of the participants with similar longitudinal patterns across four IC domains: cognition, locomotion, psychology, and vitality. Five IC multi-trajectory groups were determined: low in all domains (8.4%), low locomotion (24.6%), low psychological domain (16.7%), robust (i.e., high in all domains except vitality; 28.3%), and robust with high vitality (22.0%). Compared to the best trajectory group (i.e., robust with high vitality), elevated levels of plasma interleukin-6 (IL-6), tumor necrosis factor receptor-1 (TNFR-1), and growth differentiation factor-15 (GDF-15) were associated with a higher risk of belonging to the "low in all domains" group (IL-6: relative risk ratio (RRR) [95% CI] = 1.42 [1.07 - 1.88]; TNFR-1: RRR = 1.46 [1.09 - 1.96]; GDF-15: RRR = 1.99 [1.45 - 2.73]). Higher IL-6 and GDF-15 also increased the risk of being in the "low locomotion" group. GDF-15 outperformed other biomarkers by showing the strongest associations with IC trajectory groups. Our findings found that plasma biomarkers reflecting inflammation and mitochondrial impairment distinguished older people with multi-impaired IC trajectories from those with high-stable IC.
内在能力 (IC) 是指身体和心理能力的综合,在不同个体之间以不同的速度和模式下降。我们旨在研究纵向 IC 轨迹与两种衰老标志的血浆生物标志物之间的关联,这两种衰老标志是慢性炎症和线粒体功能障碍。从多领域阿尔茨海默病预防试验 (MAPT) 中,我们纳入了 1271 名居住在社区的老年人(平均[标准差]年龄=76.0[4.3]岁),他们在四年内有 IC 数据。进行基于群组的多轨迹建模,以识别在四个 IC 领域(认知、运动、心理和活力)具有相似纵向模式的参与者聚类。确定了五个 IC 多轨迹组:所有领域都低(8.4%)、运动领域低(24.6%)、心理领域低(16.7%)、稳健(即除活力外所有领域都高;28.3%)和活力高的稳健(22.0%)。与最佳轨迹组(即活力高的稳健组)相比,较高水平的血浆白细胞介素-6 (IL-6)、肿瘤坏死因子受体-1 (TNFR-1) 和生长分化因子-15 (GDF-15) 与属于“所有领域都低”组的风险增加相关(IL-6:相对风险比 (RRR) [95%CI] = 1.42 [1.07-1.88];TNFR-1:RRR = 1.46 [1.09-1.96];GDF-15:RRR = 1.99 [1.45-2.73])。较高的 IL-6 和 GDF-15 也增加了属于“运动领域低”组的风险。GDF-15 通过显示与 IC 轨迹组的最强关联,优于其他生物标志物。我们的研究结果发现,反映炎症和线粒体损伤的血浆生物标志物可将 IC 轨迹多受损的老年人与具有高稳定性 IC 的老年人区分开来。
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