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

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

doi:10.1038/s41598-022-15578-9

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 language	English
Article number	11290
Number of pages	8
Journal	Scientific Reports
Volume	12
Early online date	4 Jul 2022
DOIs	https://doi.org/10.1038/s41598-022-15578-9
Publication status	Published - 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/.

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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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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PublishedFinal published version, 2.78 MBLicence: CC BY

Cite this

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title = "Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer{\textquoteright}s disease",

abstract = "Emerging evidence has linked Alzheimer{\textquoteright}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.",

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

Abstract

Bibliographical note

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Keywords

ASJC Scopus subject areas

UN SDGs

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