title: Age-related impairment of T cell-induced skeletal muscle precursor cell function.
abstract: Sarcopenia is the age-associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age-associated loss of muscle precursor cell (MPC) functionality contributes to sarcopenia. The objectives of the present study were to examine the influence of activated T cells on MPCs and determine whether an age-related defect in this signaling occurs. MPCs were collected from the gastrocnemius and plantaris of 3-mo-old (young) and 32-mo-old (old) animals. Splenic T cells were harvested using anti-CD3 Dynabead isolation. T cells were activated for 48 h with costimulation of 100 IU/ml interleukin-2 (IL-2) and 5 μg/ml of anti-CD28. Costimulation increased 5-bromo-2'-deoxyuridine incorporation of T cells from 13.4 ± 4.6% in control to 64.8 ± 6.0% in costimulated cells. Additionally, T cell cytokines increased proliferation on MPCs isolated from young muscle by 24.0 ± 5.7%, whereas there was no effect on MPCs isolated from aged muscle. T cell cytokines were also found to be a chemoattractant. T cells were able to promote migration of MPCs isolated from young muscle; however, MPCs isolated from aged muscle did not respond to the T cell-released chemokines. Conversely, whereas T cell-released cytokines did not affect myogenesis of MPCs isolated from young animals, there was a decrease in MPCs isolated from old animals. These data suggest that T cells may play a critical role in mediating MPC function. Furthermore, aging may alter T cell-induced MPC function. These findings have implications for developing strategies aimed at increasing MPC migration and proliferation leading to an improved regenerative capacity of aged skeletal muscle.
authors.affiliation: Medical Sciences Division, Northern Ontario School of Medicine, 955 Oliver Rd., Thunder Bay, Ontario, Canada.
authors.forename: Breanna R
authors.initials: BR
authors.lastname: Dumke
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Lees
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D024510:Muscle Development / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology
chemical_list: D016207:Cytokines