Transcriptomic analysis of elderly women with low muscle mass: association with immune system pathway

Autor(es)

Neto, Levi H. Jales ^[1] ; Hounkpe, Bidossessi W. ^[1] ; Fernandes, Georgea H. ^[1] ; Takayama, Liliam ^[1] ; Lopes, Neuza H. M. ^[2] ; Pereira, Alexandre C. ^[3] ; Pereira, Rosa M. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Rheumatol Div, Bone Metab Lab, FMUSP, Fac Med, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Coracao InCor, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Coracao InCor, Lab Genet & Mol Cardiol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AGING-US; v. 13, n. 17, p. 20992-21008, SEP 15 2021.
• Citações Web of Science: 0

Resumo

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 (vertical bar beta coefficient vertical bar 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. (AU)

• Processo FAPESP: 16/00006-7 - Avaliação de parâmetros do metabolismo ósseo por HR-pQCT e histomorfometria em pacientes com artrite reumatoide e com artrite idiopática juvenil: associação com variáveis clínicas e genéticas
• Beneficiário: Eduardo Ferreira Borba Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/14223-5 - Avaliação de Parâmetros do Metabolismo Ósseo por HR-pQCT e Histomorfometria em Pacientes com Artrite Reumatoide e com Artrite Idiopática Juvenil: Associação com Variáveis Clínicas e Genéticas
• Beneficiário: Bidossessi Wilfried Hounkpe
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado