In silico virtual knockout identifies PXDNL as a fibroblast-specific driver of sarcopenia and GABA as a potential modulator.

Wei Cui

Jilin Sport University, Jilin, 130022, China. Electronic address: [email protected] Sport University, Jilin, 130022, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Sarcopenia lacks causal mechanisms and translatable targets. We integrated virtual gene knockout with multi-omics (n = 238 biopsies, 5 GEO cohorts) and single-cell RNA-seq (n = 10, 12,847 cells) to identify fibroblast-specific drivers. After ComBat batch correction, WGCNA identified a red module (690 genes, r = 0.74, P < 0.001) intersecting with 304 differentially expressed genes (|log

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Research summary

The paper identifies PXDNL as a fibroblast-specific driver of sarcopenia and suggests GABA as a potential modulator. The research addresses a specific mechanism related to muscle loss in aging, which is a significant aspect of the aging process and its impact on longevity.

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