Marzetti Emanuele, Guerra Flora, Calvani Riccardo, Marini Federico, Biancolillo Alessandra, Gervasoni Jacopo, Primiano Aniello, Coelho-Júnior Hélio José, Landi Francesco, Bernabei Roberto, Bucci Cecilia, Picca Anna
Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy.
Front Cell Dev Biol. 2020 Sep 22;8:564417. doi: 10.3389/fcell.2020.564417. eCollection 2020.
Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The multifaceted pathophysiology of this condition recapitulates all hallmarks of aging making the identification of specific biomarkers challenging. In the present study, we explored the relationship among three processes that are thought to be involved in PF&S (i.e., systemic inflammation, amino acid dysmetabolism, and mitochondrial dysfunction). We took advantage of the well-characterized cohort of older adults recruited in the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study to preliminarily combine in a multi-platform analytical approach inflammatory biomolecules, amino acids and derivatives, and mitochondrial-derived vesicle (MDV) cargo molecules to evaluate their performance as possible biomarkers for PF&S. Eleven older adults aged 70 years and older with PF&S and 10 non-sarcopenic non-frail controls were included in the analysis based on the availability of the three categories of biomolecules. A sequential and orthogonalized covariance selection-linear discriminant analysis (SO-CovSel-LDA) approach was used for biomarkers selection. Of the 75 analytes assayed, 16 had concentrations below the detection limit. Within the remaining 59 biomolecules, So-CovSel-LDA selected a set comprising two amino acids (phosphoethanolamine and tryptophan), two cytokines (interleukin 1 receptor antagonist and macrophage inflammatory protein 1β), and MDV-derived nicotinamide adenine dinucleotide reduced form:ubiquinone oxidoreductase subunit S3 as the best predictors for discriminating older people with and without PF&S. The evaluation of these biomarkers in larger cohorts and their changes over time or in response to interventions may unveil specific pathogenetic pathways of PF&S and identify new biological targets for drug development.
身体虚弱和肌肉减少症（PF&S）是一种典型的老年疾病，其特征是身体功能下降和肌肉量低。这种疾病的多方面病理生理学概括了衰老的所有特征，使得识别特定的生物标志物具有挑战性。在本研究中，我们探讨了被认为与PF&S相关的三个过程（即全身炎症、氨基酸代谢紊乱和线粒体功能障碍）之间的关系。我们利用在“老年人肌肉减少症和身体虚弱相关生物标志物”（BIOSPHERE）研究中招募的特征明确的老年人群队列，采用多平台分析方法，初步将炎症生物分子、氨基酸及其衍生物以及线粒体衍生囊泡（MDV）货物分子结合起来，评估它们作为PF&S可能生物标志物的性能。基于三类生物分子的可获得性，分析纳入了11名70岁及以上患有PF&S的老年人和10名非肌肉减少症非虚弱的对照者。采用顺序和正交协方差选择-线性判别分析（SO-CovSel-LDA）方法进行生物标志物选择。在检测的75种分析物中，16种的浓度低于检测限。在其余59种生物分子中，SO-CovSel-LDA选择了一组包括两种氨基酸（磷酸乙醇胺和色氨酸）、两种细胞因子（白细胞介素1受体拮抗剂和巨噬细胞炎性蛋白1β）以及MDV衍生的还原型烟酰胺腺嘌呤二核苷酸：泛醌氧化还原酶亚基S3的生物分子，作为区分患有和未患有PF&S的老年人的最佳预测指标。在更大的队列中对这些生物标志物进行评估，以及它们随时间的变化或对干预的反应，可能会揭示PF&S的特定发病机制途径，并确定药物开发的新生物学靶点。
