Activités de recherche

Muscle atrophy is one of the main deleterious consequences of ageing, diseases (e.g. cancers and AIDS), and physical inactivity. It is especially detrimental to locomotion, heat production, and metabolism thus leading to frailty, increased dependency and metabolic disorders. Apart from being a major clinical problem for older people, muscle loss is also observed during physical inactivity, which has become a major leading cause of death worldwide. Although basic knowledge regarding the underlying mechanisms of muscle atrophy is continuously growing, essentially from rodent models and clinical trials in humans, there are still no efficient therapeutic strategies for its prevention and treatment.

Hibernating bears exhibit a strong and unique ability to preserve muscle mass in conditions of muscle disuse and food deprivation, conditions during which muscle atrophy is observed in human. Bears remain inactive in winter during up to seven months without arousal episodes (without eating, drinking, urinating or defecating), with only very limited loss in muscle protein content and strength, whereas muscle and fibre cross-sectional area are preserved.

Underlying mechanisms have not been understood yet, but our recent demonstration of trans-species effects of bear serum controlling protein degradation in cultured human muscle cell holds promising potential. By inducing a hibernation-like phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.

Publications les plus marquantes

• Han Y, Miao W, Hao Z, An N, Yang Y, Zhang Z, Chen J, Storey KB, Lefai E, Chang H. The Protective Effects on Ischemia-Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor-Arousal Cycle of Hibernation. Int J Mol Sci. 2022 ; 23(18):10248. doi: 10.3390/ijms231810248. PMID: 36142152
• Cussonneau L, Boyer C, Brun C, Deval C, Loizon E, Meugnier E, Gueret E, Dubois E, Taillandier D, Polge C, Béchet D, Gauquelin-Koch G, Evans AL, Arnemo JM, Swenson JE, Blanc S, Simon C, Lefai E, Bertile F, Combaret L. Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear. Cells. 2021 Jul 23;10(8):1873. doi: 10.3390/cells10081873. PMID: 34440643
• Givre L, Crola Da Silva C, Swenson JE, Arnemo JM, Gauquelin-Koch G, Bertile F, Lefai E, Gomez L. Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction. Front Cardiovasc Med. 2021 ; 16;8:687501. doi: 10.3389/fcvm.2021.687501. PMID: 34336951
• Boyer C, Cussonneau L, Brun C, Deval C, Pais de Barros JP, Chanon S, Bernoud-Hubac N, Daira P, Evans AL, Arnemo JM, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Combaret L, Bertile F, Lefai E. Specific shifts in the endocannabinoid system in hibernating brown bears. Front Zool. 2020; 17(1):35. doi: 10.1186/s12983-020-00380-y. PMID: 33292302
• Chanon S, Chazarin B, Toubhans B, Durand C, Chery I, Robert M, Vieille-Marchiset A, Swenson JE, Zedrosser A, Evans AL, Brunberg S, Arnemo JM, Gauquelin-Koch G, Storey KB, Simon C, Blanc S, Bertile F, Lefai E. Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells. Sci Rep. 2018 ; 8(1):5525. doi: 10.1038/s41598-018-23891-5. PMID: 29615761

Autres liens

PROTEOSTASIS

ORCID : https://orcid.org/0000-0002-3042-7801