Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease

Panagiotis Giannos, Konstantinos Prokopidis, Stuart M. Raleigh, Eirini Kelaiditi, Mathew Hill

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    Abstract

    Emerging evidence has linked Alzheimer’s disease (AD) onset with musculoskeletal aging via a muscle-brain crosstalk mediated by dysregulation of the mitochondrial microenvironment. This study investigated gene expression profiles from skeletal muscle tissues of older healthy adults to identify potential gene biomarkers whose dysregulated expression and protein interactome were involved in AD. Screening of the literature resulted in 12 relevant microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880) in musculoskeletal aging and (GSE4757, GSE5281, GSE16759, GSE28146, GSE48350, GSE84422) in AD. Retrieved differentially expressed genes (DEGs) were used to construct two unique protein–protein interaction networks and clustering gene modules were identified. Overlapping module DEGs in the musculoskeletal aging and AD networks were ranked based on 11 topological algorithms and the five highest-ranked ones were considered as hub genes. The analysis revealed that the dysregulated expression of the mitochondrial microenvironment genes, NDUFAB1, UQCRC1, UQCRFS1, NDUFS3, and MRPL15, overlapped between both musculoskeletal aging and AD networks. Thus, these genes may have a potential role as markers of AD occurrence in musculoskeletal aging. Human studies are warranted to evaluate the functional role and prognostic value of these genes in aging populations with sarcopenia and AD.

    Original languageEnglish
    Article number11290
    Number of pages8
    JournalScientific Reports
    Volume12
    Early online date4 Jul 2022
    DOIs
    Publication statusPublished - 4 Jul 2022

    Bibliographical note

    Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

    Funder

    Funding Information:
    The creation of Fig. 1 was ensued using Cytoscape (https://cytoscape.org/ ) and Fig. 2 using Biorender (https://biorender.com ).

    Keywords

    • Ageing
    • Alzheimer's disease
    • Musculoskeletal system

    ASJC Scopus subject areas

    • General

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