A mechanism capable of preserving muscle mass

Skeletal muscle is the most abundant tissue of the human body (about 40%) and it plays essential role in locomotion and vital functions (heart rate, breathing). During aging, in a large majority of individuals a loss of muscle mass, quality and strength occurs: this is called sarcopenia. This state, leading to disability and dependence, was declared as a disease in 2016 by the World Health Organization. By studying the young and aging muscles in mice, researchers from the Myology Research Center (Sorbonne Universite-Inserm) of the Institute of Myology identified a protein, CaVbeta1E that activates the factor GDF5. This mechanism promotes the prevention of sarcopenia by maintaining the muscle mass and strength of aged mice. The team discovered the CaVbeta1E protein in humans and showed that its expression correlated with the loss of muscle mass of the elderly. Published today in

Science Translational Medicine

, this study opens a new field of activity in the development of therapeutic strategies against the muscular decline associated with aging.

Sarcopenia is defined by a progressive and generalized loss of mass, strength and quality of the entire musculature from the age of 50, which may ultimately lead to a decrease of more than 30% of the initial muscle mass. Its consequences are numerous: increased risk of falls (the leading cause of death related to an injury in people over 65), increased length of hospital stay, infectious risks, dependence. Qualified as “Disease” in 2016 by the World Health Organization, sarcopenia, currently affects about one in five European over 55 year old (30 million by 2045): it is a major public health issue.

The muscle mass depends on the innervation and the excitation (nerve)-contraction (muscle) coupling. It can vary according to environmental changes, increase (hypertrophy), as after muscle training, or decrease (atrophy) as during prolonged immobilization, nerve damage, in a pathological context or during aging. The muscle’s response to atrophy is the establishment of molecular mechanisms that tend to limit its loss.

As part of research for the prevention and / or treatment of sarcopenia, France Pietri-Rouxel and Sestina Falcone, team leader and researcher at the Institute of Myology, have defined the role of a protein, CaVβ1E, in the adult mouse muscle. CaVβ1E is a protein normally expressed in muscle in the embryo. After alteration of the peripheral nerve, the team observed, for the first time, the re-expression of this protein in the adult muscle. Here, it activates GDF5 to counter atrophy due to denervation. During aging, the mechanism involving the CaVbeta1E protein is impaired, thereby causing the muscle’s inability to respond to its mass loss. The team tested the efficacy of CaVbeta1E or GDF5 overexpression in 78 week-old mice (the equivalent of 70 years in humans). After several weeks of treatment, the mice no longer lost muscle mass and gained strength.On the strength of these advances, the team identified the presence of CaVbeta1E protein in humans (hCaVbeta1E) and showed that a decrease of its expression is correlated with the loss of muscle mass in elderly subjects. Currently, the team is working on pre- and clinical applications that may preserve the mass, strength and quality of muscle during aging.

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Publication: An embryonic CaVbeta1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse.

Authors: Traore; Massire1* , Gentil Christel2* , Benedetto Chiara2, Hogrel Jean-Yves3, De la Grange Pierre4, Cadot Bruno2, Benkhelifa-Ziyyat Sofia2, Julien Laura2, Lemaitre Megane5, Ferry Arnaud2, Pietri-Rouxel France2# and Falcone Sestina2#
*: co-authors; #: co-last authors.

Affiliations : 1Inovarion F-75013, Paris France ; 2Sorbonne Universite;, Centre de Recherche en Myologie, UM76 /INSERM U974 Institut de Myologie, F-75013, Paris, France ; 3Institut de Myologie, GH Pitie-Salpetriere, F-75013, Paris France; 4Genosplice, F-75005, Paris, France;5Sorbonne Universite;, INSERM, UMS28, F-75013, Paris, France