Abstract
Objectives
Skeletal muscle (SkM) regeneration post injury is reliant on SkM-specific stem cells (muscle progenitor cells [MPCs]) and a well-orchestrated myogenic program. The regenerative process is impaired with advancing age, potentiating pathological SkM remodeling (infiltration of fat and fibrotic tissues). We have previously demonstrated that the nutritionally non-essential amino acids serine (Ser) and glycine (Gly) are required for early stages of SkM regeneration (MPC proliferation). However, Ser and Gly availability (SkM and circulating) declines with aging. The objective was to test the hypothesis that reduced endogenous Ser/Gly during regeneration promotes pathological SkM remodeling in aged animals.
Methods
Old mice (∼20 months of age) were given a Ser/Gly depleted diet (SGdep) or an isonitrogenous, isoenergetic diet containing Ser/Gly (SGcont) for 4 weeks followed by notexin-induced injury to the tibialis anterior (TA) SkM. At 28 days post injury the TA was harvested and histological analysis of SkM morphology (H&E and immunofluorescence [IF]) and gene expression analyses (qPCR) were completed.
Results
Old mice receiving the SGdep diet had a shift toward reduced myofiber size and enhanced adipocyte infiltration in the SkM. Adipocyte infiltration was confirmed with IF of perilipin-1, an adipocyte marker. Uninjured mice on the SGdep diet did not demonstrate altered SkM morphology. Gene expression analysis of differentially expressed genes underlying SkM remodeling (reduced myofiber size and increased fat infiltration) with SGdep is ongoing.
Conclusions
Reduced Ser and Gly availability following injury instigates SkM remodeling in old mice, which could explain in part age-related impairments in SkM regeneration. This research underscores the essentiality of Ser and Gly for the SkM regenerative process particularly with advancing age.
Funding Sources
Canadian Institutes of Health Research Doctoral Foreign Study Award to BG.