The HIF-1α Pathway Regulates Satellite Cell Fate During Aging Through Histone Lactylation.

ABSTRACT: Aging-associated sarcopenia is driven in part by the progressive loss of type II glycolytic fibers and the functional decline of their resident stem cells, the satellite cells (SCs). We show here that these defects result from attenuation of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway and can be reversed by pharmacological HIF-1α reactivation. In the tibialis anterior muscle of 18-month-old C57BL/6J mice, HIF-1α protein abundance decreased by ≈46% and canonical targets (Vegfa, Egln1) were downregulated in freshly isolated SCs. Treatment of aged SCs with the prolyl hydroxylase inhibitor roxadustat (FG-4592) for 48 h restored HIF signaling, upregulated glycolytic enzymes (HK2, GAPDH, ALDO) and the lactate transporter MCT4, and increased intracellular lactate by 1.9-fold. Incre

SUBMITTER: Piccoli M 

PROVIDER: S-EPMC12904840 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature