Coto-Montes Ana, González-Blanco Laura, Antuña Eduardo, Menéndez-Valle Iván, Bermejo-Millo Juan Carlos, Caballero Beatriz, Vega-Naredo Ignacio, Potes Yaiza
Department of Cell Biology and Morphology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Av. del Hospital Universitario, Oviedo, Spain.
Front Cell Dev Biol. 2021 Dec 2;9:792825. doi: 10.3389/fcell.2021.792825. eCollection 2021.
Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones. Overweight is a recognized cause of frailty in aging, so we studied the altered mechanisms in overweight independent elderly and evaluated their aggravation in dependent elderly. This evidence of the evolution of previously altered mechanisms would significantly support their role as real biomarkers of frailty. The results showed a preponderant role of autophagy in interactome control at both different functional points, modulating other essential mechanisms in the cell, such as mitochondrial capacity or oxidative stress. Thus, the overweight provoked in the muscle of the elderly an overload of autophagy that kept cell survival in apparently healthy individuals. This excessive and permanent autophagic effort did not seem to be able to be maintained over time. Indeed, in dependent elderly, the muscle showed a total autophagic inactivity, with devastating effects on the survival of the cell, which showed clear signs of apoptosis, and reduced functional capacity. The frail elderly are in a situation of weakness that is a precursor of dependence that can still be prevented if detection is early. Hence biomarkers are essential in this context.
生物标志物是准确诊断和有效预防的重要工具，但其验证仍是一个悬而未决的挑战，限制了它们的实用性，对于像衰弱这样复杂的概念更是如此。肌肉减少症与衰弱有多种共同机制，这使其成为提供可靠衰弱生物标志物的有力候选者。基于这一前提，我们研究了衰弱状态下细胞相互作用组从独立患者到依赖患者的时间演变。超重是衰老过程中公认的衰弱原因，因此我们研究了超重独立老年人中改变的机制，并评估了其在依赖老年人中的加重情况。先前改变的机制演变的这一证据将显著支持它们作为衰弱真正生物标志物的作用。结果表明，自噬在两个不同功能点的相互作用组控制中起主要作用，调节细胞中的其他重要机制，如线粒体功能或氧化应激。因此，老年人肌肉中的超重引发了自噬过载，使明显健康个体的细胞得以存活。这种过度且持续的自噬努力似乎无法长期维持。事实上，在依赖老年人中，肌肉表现出完全的自噬无活性，对细胞存活产生毁灭性影响，细胞出现明显的凋亡迹象，功能能力下降。衰弱的老年人处于虚弱状态，这是依赖的先兆，如果早期检测仍可预防。因此，在这种情况下生物标志物至关重要。
