Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducibl...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-07, Vol.23 (13), p.7114
Main Authors: Cirillo, Federica, Mangiavini, Laura, La Rocca, Paolo, Piccoli, Marco, Ghiroldi, Andrea, Rota, Paola, Tarantino, Adriana, Canciani, Barbara, Coviello, Simona, Messina, Carmelo, Ciconte, Giuseppe, Pappone, Carlo, Peretti, Giuseppe Maria, Anastasia, Luigi
Format: Article
Language:English
Subjects:
Age
Aging
Angiogenesis
Atrophy
Biopsy
Blood vessels
Cardiovascular diseases
Cell cycle
Gene expression
Genes
Genotype & phenotype
HIF-1α
Homeostasis
Hypoxia
Hypoxia-inducible factor 1a
Metabolic disorders
Morbidity
Muscles
Musculoskeletal system
Myoblasts
Older people
Pharmacology
Population
Proteins
Public health
Sarcopenia
Satellite cells
Skeletal muscle
Stem cells
Vascularization
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Summary:Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23137114