title: The lymphocyte secretome from young adults enhances skeletal muscle proliferation and migration, but effects are attenuated in the secretome of older adults.
abstract: Older people experience skeletal muscle wasting, in part due to impaired proliferative capacity of quiescent skeletal muscle satellite cells which can be reversed by exposure to young blood. To investigate the role of immune cells in muscle regeneration, we isolated lymphocytes from whole blood of young and older healthy volunteers and cultured them with, or without, anti-CD3/CD28 activators to induce release of cytokines, interleukins, and growth factors into the media. The secreted proteins were collected to prepare a conditioned media, which was subsequently used to culture C2C12 myoblasts. The conditioned media from the activated young lymphocytes increased the rate of proliferation of myoblasts by around threefold (P < 0.005) and caused an approximate fourfold (P < 0.005) increase in migration compared with nonactivated lymphocyte control media. These responses were characterized by minimal myotube formation (2%), low fusion index (5%), low myosin heavy chain content, and substantial migration. In contrast, myoblasts treated with conditioned media from activated old lymphocytes exhibited a high degree of differentiation, and multi-nucleated myotube formation that was comparable to control conditions, thus showing no effect on proliferation or migration of myoblasts. These results indicate that secreted proteins from lymphocytes of young people enhance the muscle cell proliferation and migration, whereas secreted proteins from lymphocytes of older people may contribute to the attenuated skeletal muscle satellite cell proliferation and migration.
authors.affiliation: Healthcare Science Research Centre, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Al-Dabbagh
authors.affiliation: Healthcare Science Research Centre, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
authors.forename: Jamie S
authors.initials: JS
authors.lastname: McPhee
authors.affiliation: Healthcare Science Research Centre, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Murgatroyd
authors.affiliation: Myology Center of Research, UM76 - UPMC Sorbonne Universités/U974 - Inserm/FRE3617 - CNRS/AIM, Paris Cedex 13, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Research Institute for Sport & Exercise Sciences, School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Stewart
authors.affiliation: Healthcare Science Research Centre, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK n.al-shanti@mmu.ac.uk.
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Shanti
keywords: Differentiation; Myoblasts; immune system; lymphocytes; proliferation; secretome