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.

Activated Lymphocytes Secretome Inhibits Differentiation and Induces Proliferation of C2C12 Myoblasts

“…The immune system responds to muscle damage with a complex sequence of immune reactions leading to recruitments of inflammatory and immune cells that ultimately lead to satellite cell activation, proliferation and eventually muscle regeneration. In the last decade, there has been a remarkable increase in the number of studies regarding the interaction of exercise and the immune system [10,15,30,31]. However, a role of the acquired immune system, in particular T-lymphocytes, in muscle function and performance has not been investigated, but needs to be elucidated.…”

“…One study, using scid/mdx ( mdx : dystrophic mouse, scid : immunodeficient mouse) as model to examine possible interactions between skeletal muscle and T cells, demonstrated that these mice exhibited reduced muscle fibrosis and degeneration [14]. Recently, Dumke and Lees investigated the influence of activated T lymphocytes on the regeneration capacity of muscle precursor cells [15]. In this study, rat satellite cells were isolated from the gastrocnemius and plantaris muscles of 3 and 32 month old animals and were cultured with splenic activated T cells.…”

Primary human muscle precursor cells obtained from young and old donors produce similar proliferative, differentiation and senescent profiles in culture

“…These findings are in general agreement with previous work. For example, there is evidence to suggest that MPCs obtained from elderly animals can proliferate and differentiate similarly to that of young animals (Dumke & Lees, 2011). Single fibre grafting experiments have shown that satellite cells from old animals possess an equivalent in vivo myogenic and self-renewal potential to that of young animals (Collins et al, 2007).…”

The lymphocyte secretome from young adults enhances skeletal muscle proliferation and migration, but effects are attenuated in the secretome of older adults

“…Consequently, contraction‐ or trauma‐induced muscle damage accumulates while aging through cycles of insufficient regeneration (Conboy et al. ; Dumke and Lees ).…”

“…The failure to activate and proliferate satellite cells in older age is not necessarily only related to intrinsic deficits, but the microenvironment is also implicated (Dumke and Lees ; Barberi et al. ).…”