Division of Geriatric Medicine, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America.
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America.
PLoS One. 2020 Sep 4;15(9):e0238877. doi: 10.1371/journal.pone.0238877. eCollection 2020.
A recent study identified progranulin as a candidate biomarker for frailty, based on gene expression databases. In the present study, we investigated associations between serum progranulin levels and frailty in a population-based sample of late middle-age and older adults.
We utilized a cohort study that included 358 African Americans (baseline ages 49-65). Frailty was assessed by three established methods: the interview-based FRAIL scale, the Cardiovascular Health Study (CHS) frailty scale that includes performance-based measurements, and the Frailty Index (FI) that is based on cumulative deficits. Serum levels of the following proteins and metabolites were measured: progranulin, cystatin C, fructosamine, soluble cytokine receptors (interleukin-2 and -6, tumor necrosis factor α-1 and -2), and C-reactive protein. Sarcopenia was assessed using the SARC-F index. Vital status was determined by matching through the National Death Index (NDI).
Serum progranulin levels were associated with frailty for all indices (FRAIL, CHS, and FI) but not with sarcopenia. Inflammatory markers indicated by soluble cytokine receptors (sIL-2R, sIL-6R, sTNFR1, sTNFR2) were positively associated serum progranulin. Increased serum progranulin levels at baseline predicted poorer outcomes including future frailty as measured by the FRAIL scale and 15-year all-cause mortality independent of age, gender, and frailty.
Our findings suggest that serum progranulin levels may be a candidate biomarker for physical frailty, independent of sarcopenia. Further studies are needed to validate this association and assess the utility of serum progranulin levels as a potential biomarker for prevalent frailty, for risk for developing incident frailty, and for mortality risk over and above the effect of baseline frailty.
一项基于基因表达数据库的最新研究表明，颗粒蛋白前体(progranulin)是 frail 的候选生物标志物。本研究旨在调查中年后期及以上人群中血清颗粒蛋白前体水平与 frail 的相关性。
我们利用一项队列研究，该研究纳入了 358 名非裔美国人（基线年龄 49-65 岁）。采用三种公认的方法评估 frail：基于访谈的 FRAIL 量表、包含基于表现的测量的心血管健康研究（CHS） frail 量表以及基于累积缺陷的 frail 指数（FI）。测量了以下蛋白质和代谢物的血清水平：颗粒蛋白前体、胱抑素 C、果糖胺、可溶性细胞因子受体（白细胞介素-2 和 -6、肿瘤坏死因子-α-1 和 -2）和 C 反应蛋白。使用 SARC-F 指数评估肌少症。通过与国家死亡指数（NDI）匹配确定生存状况。
血清颗粒蛋白前体水平与所有 frail 指数（FRAIL、CHS 和 FI）相关，但与肌少症无关。可溶性细胞因子受体（sIL-2R、sIL-6R、sTNFR1、sTNFR2）所代表的炎症标志物与血清颗粒蛋白前体呈正相关。基线时血清颗粒蛋白前体水平升高预示着较差的结局，包括未来根据 FRAIL 量表评估的 frail 以及 15 年全因死亡率，这与年龄、性别和 frail 无关。
我们的研究结果表明，血清颗粒蛋白前体水平可能是 frail 的候选生物标志物，与肌少症无关。需要进一步研究来验证这一关联，并评估血清颗粒蛋白前体水平作为现患 frail、发生 frail 的风险以及超过基线 frail 效应的死亡率风险的潜在生物标志物的效用。
