☆ 4.7 Article

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

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Volume 23, Issue 13, Pages -

Publisher

MDPI

DOI: 10.3390/ijms23137114

Keywords

HIF-1 alpha; sarcopenia; atrophy; hypoxia; satellite cells

Funding

Italian Ministry of Health to IRCCS Policlinico San Donato
IRCCS Orthopaedic Galeazzi Hospital
Department of Biomedical Sciences for Health, University of Milan

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Abstract

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. This study found that the hypoxia inducible factor HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis.

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-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1 alpha could prevent and counteract sarcopenia.

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HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia

Shiqiang Liu, Pengyu Fu, Kaiting Ning, Rui Wang, Baoqiang Yang, Jiahui Chen, Huiyun Xu

Summary: Exposure to high altitude leads to skeletal muscle atrophy, but the role of irisin in hypoxia-induced skeletal muscle atrophy is unclear. This study found that hypoxia exposure reduced body weight and muscle mass, as well as grip strength and exercise duration in mice. Hypoxia also decreased the expression of irisin and its precursor protein FNDC5 in skeletal muscle. In vitro experiments showed that hypoxia reduced FNDC5 expression and increased HIF-1 alpha. Additionally, inhibiting HIF-1 alpha rescued the decline in myotube area and diameter caused by hypoxia.