Mitochondrial dysfunction as a biomarker of frailty: The FRAMITO study protocol

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Archives of gerontology and geriatrics Pub Date : 2025-02-26 DOI:10.1016/j.archger.2025.105803

Edoardo Locatelli , Barbara Torsello , Sofia De Marco , Martina Lombardi , Francesca Remelli , Giulia Pampolini , Elena Ferrighi , Marialucia Bursi , Andrea Bellotti , Valentina Pasquale , Giacomo Ducci , Ouldouz Navaei , Raffaella Candeloro , Maria Cristina Ferrara , Wenxiang Guo , Eleonora Cucini , Giuseppe Bellelli , Massimiliano Castellazzi , Elena Sacco , Giuseppe Paglia , Caterina Trevisan

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引用次数: 0

Abstract

Frailty syndrome often coexists with multimorbidity, sharing several risk factors and outcomes. Therefore, considering multimorbidity when exploring frailty biomarkers may deepen our understanding of these conditions’ pathophysiology. In this regard, most studies focused on inflammation, but markers of mitochondrial dysfunction, such as mitochondrial DNA damage, cell respiratory impairment, and oxidative stress, are less explored. The FRAMITO project aims to evaluate mitochondrial dysfunction in frailty, with and without multimorbidity. This cross-sectional study will enroll 75 individuals aged ≥65 years from inpatient and outpatient clinics at the Geriatrics Units of the University Hospital of Ferrara (Ferrara, Italy) and Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy). Participants will be categorized into three groups: 25 without frailty and multimorbidity, 25 with frailty but not multimorbidity, and 25 with frailty and multimorbidity. Blood samples will be collected to isolate Peripheral Blood Mononuclear Cells. Frailty biomarkers will be identified using untargeted metabolomics and functional studies on mitochondrial dysfunctions in PBMCs and their subpopulations, evaluating mitochondrial DNA damage, mitochondrial and glycolytic cellular bioenergetics, and intracellular reactive oxygen species. This project will advance our understanding of mitochondrial dysfunctions in frailty, particularly when combined with multimorbidity, revealing potential synergistic effects.

Clinicaltrial.gov registration number

NCT06433427.

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线粒体功能障碍作为脆弱的生物标志物：FRAMITO研究方案

虚弱综合征通常与多种疾病共存，共享多个危险因素和结果。因此，在探索脆弱生物标志物时考虑多发病可能会加深我们对这些疾病病理生理学的理解。在这方面，大多数研究都集中在炎症上，但线粒体功能障碍的标志物，如线粒体DNA损伤、细胞呼吸损伤和氧化应激，却很少被探索。FRAMITO项目旨在评估有或无多病的虚弱线粒体功能障碍。这项横断面研究将招募75名年龄≥65岁的患者，他们来自费拉拉大学医院（Ferrara，意大利）和基金会IRCCS San Gerardo dei Tintori老年科（Monza，意大利）的住院和门诊。参与者将被分为三组：25名没有虚弱和多重疾病的人，25名虚弱但没有多重疾病的人，25名虚弱和多重疾病的人。采集血样分离外周血单核细胞。脆弱性生物标志物将通过非靶向代谢组学和线粒体功能障碍的功能研究在pbmc及其亚群中进行鉴定，评估线粒体DNA损伤、线粒体和糖酵解细胞生物能量学以及细胞内活性氧。该项目将促进我们对衰弱中线粒体功能障碍的理解，特别是当合并多种疾病时，揭示潜在的协同效应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of gerontology and geriatrics 医学-老年医学

CiteScore

7.30

自引率

5.00%

发文量

198

审稿时长

16 days

期刊介绍： Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.