PLX082878

GSE139213: The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia [TSCmKO data set].

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Purpose: Sustained muscle fiber-specific mTORC1 activity, through deletion of the mTORC1 upstream inhibitor Tsc1, drives progressive muscle wasting and weakness reminiscent of sarcopenia. We aimed to characterise gene expression changes coinciding with the development of sarcopenia-like features in TSCmKO mice.; Methods: Extensorum digitorum longus (EDL) muscles from 3- (weak phenotype) and 9-month-old (severe phenotype) TSCmKO and littermate control mice (Tsc1 floxed, HSA-Cre negative) treated with either vehicle or rapamycin (8 mg.kg.min-1) for 3 days were processed and sequenced.; Results: The principal component analysis showed two major gene expression patterns. The first pattern represents an aging-like pattern with gene expression remaining stable between 3 and 9 months in wild type mice, but changing between 3 and 9 months in TSCmKO mice. The second pattern seems to represent early alterations in TSCmKO mice compared to WT, which subside between 3 and 9 months in TSCmKO. Importantly, when comparing changes in the gene expression in TSCmKO mice with natural aging gene expression profiles, there was a significant overrepresentation of commonly increasing and decreasing genes and an underrepresentation of oppositely regulated genes. Likewise, many of the top enriched GO terms for natural aging gene expression profiles were also enriched for genes changing the expression in the premature aging TSCmKO mice.; Conclusions: Sustained, muscle fiber-specific mTORC1 activity drives sarcopenia-like gene expression programs, and the hyperactive mTORC1 seen in sarcopenic muscle may therefore contribute to sarcopenia. SOURCE: Anastasiya Boersch (anastasiya.boersch@gmail.com) - University of Basel