Biomarkers of multimorbidity: A systematic review

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-08-13 DOI:10.1016/j.arr.2025.102870

Maria Beatrice Zazzara , Federico Triolo , Leonardo Biscetti , Ersilia Paparazzo , Marco Fiorillo , Davide Liborio Vetrano , Graziano Onder , on behalf of the BIO-SIGN Study Investigators

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引用次数: 0

Abstract

The development of multiple chronic diseases in the same individual (i.e., multimorbidity) results from the loss of homeostasis across several biological systems. Identifying pathophysiological pathways common to multiple diseases, using accessible biomarkers, could increase our understanding of multimorbidity and improve its prognostication and management. We conducted a systematic review of peer-reviewed articles published till September 2024 that investigated biomarkers of multimorbidity. Due to study heterogeneity, a synthesis without meta-analysis was performed on 43 studies employing harvest plots based on direction of effect, sample size and study quality. Findings highlight how inflammatory and metabolic biomarkers, such as interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) especially, but also triglycerides, low-density lipoprotein (LDL) cholesterol and kidney and liver markers, along with markers of neurodegeneration including Neurofilament Light Chain (NfL) and Phospho-Tau 217 (p-tau 217), were directly associated with multimorbidity. Nonetheless, evidence for hormonal and vascular activation markers, as well as more novel geroscience biomarkers, remains limited. These markers could have a key role in identifying individuals at high risk of developing or worsening multimorbidity. The review also highlights how methodological challenges, including heterogeneity in study design, populations, and multimorbidity definitions, impact on comparability and generalizability of findings. Addressing these gaps through standardized, longitudinal studies and multi-omics approaches is crucial to improve our understanding of the pathophysiological mechanisms of multimorbidity. In summary, this review outlines the independent association of diverse biomarkers with multimorbidity, opening to the possibility of identifying specific pathophysiological pathways for risk stratification and possible target of future personalized interventions.

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多病的生物标志物：系统综述。

同一个体中多种慢性疾病的发生（即多重发病）是由于多个生物系统的体内平衡丧失所致。识别多种疾病共同的病理生理途径，使用可获得的生物标志物，可以增加我们对多病的理解，并改善其预后和管理。我们对截至2024年9月发表的同行评议文章进行了系统回顾，这些文章研究了多病的生物标志物。由于研究异质性，基于效应方向、样本量和研究质量，对43项采用收获样地的研究进行综合分析，但不进行meta分析。研究结果强调炎症和代谢生物标志物，特别是白介素-6 （IL-6）和糖化血红蛋白（HbA1c），以及甘油三酯、低密度脂蛋白（LDL）胆固醇和肾脏和肝脏标志物，以及神经变性标志物，包括神经丝轻链（NfL）和磷酸化tau 217 (p-tau 217)，与多发性疾病直接相关。尽管如此，激素和血管激活标记物以及更新颖的老年科学生物标记物的证据仍然有限。这些标记可能在识别发展或恶化多重疾病的高风险个体方面发挥关键作用。该综述还强调了方法学上的挑战，包括研究设计、人群和多病定义的异质性，如何影响研究结果的可比性和普遍性。通过标准化的纵向研究和多组学方法来解决这些差距对于提高我们对多病的病理生理机制的理解至关重要。总之，本综述概述了多种生物标志物与多种疾病的独立关联，为确定特定的病理生理途径进行风险分层和未来个性化干预的可能目标提供了可能性。

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

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.