Identification of Key Genes and Pathways Associated with Frailty and Exercise Effects Using a Network and Evolutionary Approach.

Background: Frailty is an aging-associated syndrome involving a loss of physiological reserve and function, with decreased ability to recover from physical and psychosocial stress. However, the etiology and pathogenesis of frailty remain largely unknown.

Aim: This study aimed to investigate key genes involved in frailty pathogenesis, exercise effects, and their contributions.

Methods: We performed a weighted gene co-expression network analysis using a microarray dataset. By using the positive selection (PS), human accelerated region (HAR), and aging gene sets, we identified key genes for frailty and exercise-related genes.

Results: We identified magenta and pink modules that have the most significant enrichments for the evolutionally elaborated genes. A functional enrichment analysis (FEA) revealed that genes related to redox-process regulation and extracellular-matrix organization were enriched in magenta and pink modules, respectively. We observed that six of the evolutionarily imprinted genes in the modules (, , , , and ) were highly connected and showed signs of hub properties, which might play crucial roles in frailty- and exercise-related mechanisms.

Conclusions: Further investigation into the functions of the identified modules and their member genes could aid in identifying diagnostic biomarkers and therapeutic targets for frailty.