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

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.

Figure 1

The top five overlapping hub genes of clustering modules in the protein–protein interaction network of differentially expressed genes from (A) musculoskeletal aging and (B) Alzheimer’s disease. Yellow nodes constitute hub genes. MRPL15 Mitochondrial ribosomal protein L15, NDUFAB1 NADH:ubiquinone oxidoreductase subunit AB1, NDUFS3 NADH:ubiquinone oxidoreductase core subunit S3, UQCRC1 Ubiquinol-cytochrome c reductase core protein 1, UQCRFS1 Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1.

Figure 2

Dysregulated expression of mitochondrial microenvironment genes, NDUFAB1, UQCRC1, UQCRFS1, NDUFS3, and MRPL15, as marker of perturbed muscle-brain crosstalk between musculoskeletal aging and Alzheimer’s disease.