Research Paper Volume 13, Issue 17 pp 20992—21008
Transcriptomic analysis of elderly women with low muscle mass: association with immune system pathway
- 1 Bone Metabolism Laboratory, Rheumatology Division Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- 2 Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- 3 Laboratory of Genetics and Molecular Cardiology, Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
Received: May 24, 2021 Accepted: August 24, 2021 Published: September 7, 2021
https://doi.org/10.18632/aging.203505How to Cite
Copyright: © 2021 Neto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Despite the well-established association of gene expression deregulation with low muscle mass (LMM), the associated biological mechanisms remain unclear. Transcriptomic studies are capable to identify key mediators in complex diseases. We aimed to identify relevant mediators and biological mechanisms associated with age-related LMM. LMM-associated genes were detected by logistic regression using microarray data of 20 elderly women with LMM and 20 age and race-matched controls extracted from our SPAH Study (GSE152073). We performed weighted gene co-expression analysis (WGCNA) that correlated the identified gene modules with laboratorial characteristics. Gene enrichment analysis was performed and an LMM predictive model was constructed using Support Vector Machine (SVM). Overall, 821 discriminating transcripts clusters were identified (|beta coefficient| >1; p-value <0.01). From this list, 45 predictors of LMM were detected by SVM and validated with 0.7 of accuracy. Our results revealed that the well-described association of inflammation, immunity and metabolic alterations is also relevant at transcriptomic level. WGCNA highlighted a correlation of genes modules involved in immunity pathways with vitamin D level (R = 0.63, p = 0.004) and the Agatston score (R = 0.51, p = 0.02). Our study generated a predicted regulatory network and revealed significant metabolic pathways related to aging processes, showing key mediators that warrant further investigation.