Heme deficiency in skeletal muscle exacerbates sarcopenia and impairs autophagy by reducing AMPK signaling.

ABSTRACT: Heme serves as a prosthetic group in hemoproteins, including subunits of the mammalian mitochondrial electron transfer chain. The first enzyme in vertebrate heme biosynthesis, 5-aminolevulinic acid synthase 1 (ALAS1), is ubiquitously expressed and essential for producing 5-aminolevulinic acid (ALA). We previously showed that Alas1 heterozygous mice at 20-35 weeks (aged-A1^+/-s) manifested impaired glucose metabolism, mitochondrial malformation in skeletal muscle, and reduced exercise tolerance, potentially linked to autophagy dysfunction. In this study, we investigated autophagy in A1^+/-s and a sarcopenic phenotype in A1^+/-s at 75-95 weeks (senile-A1^+/-s). Senile-A1^+/-s exhibited significantly reduced body and gastrocnemius muscle weigh

SUBMITTER: Akabane T 

PROVIDER: S-EPMC11437137 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature