title: Changes in Communication between Muscle Stem Cells and their Environment with Aging.
abstract: Aging is associated with both muscle weakness and a loss of muscle mass, contributing towards overall frailty in the elderly. Aging skeletal muscle is also characterised by a decreasing efficiency in repair and regeneration, together with a decline in the number of adult stem cells. Commensurate with this are general changes in whole body endocrine signalling, in local muscle secretory environment, as well as in intrinsic properties of the stem cells themselves. The present review discusses the various mechanisms that may be implicated in these age-associated changes, focusing on aspects of cell-cell communication and long-distance signalling factors, such as levels of circulating growth hormone, IL-6, IGF1, sex hormones, and inflammatory cytokines. Changes in the local environment are also discussed, implicating IL-6, IL-4, FGF-2, as well as other myokines, and processes that lead to thickening of the extra-cellular matrix. These factors, involved primarily in communication, can also modulate the intrinsic properties of muscle stem cells, including reduced DNA accessibility and repression of specific genes by methylation. Finally we discuss the decrease in the stem cell pool, particularly the failure of elderly myoblasts to re-quiesce after activation, and the consequences of all these changes on general muscle homeostasis.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Matthew
authors.initials: M
authors.lastname: Thorley
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Malatras
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: William
authors.initials: W
authors.lastname: Duddy
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Le Gall
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler Browne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UMRS 974, F-75013, Paris, France.|INSERM UMRS 974, F-75013, Paris, France.|CNRS FRE 3617, F-75013, Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Duguez
keywords: Aging; adult stem cells; homeostasis; intercellular signaling peptides and proteins; muscles; myoblasts; skeletal