The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny

Abstract

Satellite cells are myogenic progenitors residing on the myofiber surface that support skeletal muscle repair. We used mice in which satellite cells were detected by GFP expression driven by nestin gene regulatory elements to define age-related changes in both numbers of satellite cells that occupy hindlimb myofibers and their individual performance. We demonstrate a reduction in satellite cells per myofiber with age that is more prominent in females compared to males. Satellite cell loss also persists with age in myostatin-null mice regardless of increased muscle mass. Immunofluorescent analysis of isolated myofibers from nestin-GFP/Myf5nLacZ/+ mice reveals a decline with age in the number of satellite cells that express detectable levels of βgal. Nestin-GFP expression typically diminishes in primary cultures of satellite cells as myogenic progeny proliferate and differentiate, but GFP subsequently reappears in the Pax7+ reserve population. Clonal analysis of sorted GFP+ satellite cells from hindlimb muscles shows heterogeneity in the extent of cell density and myotube formation among colonies. Reserve cells emerge primarily within high-density colonies, and the number of clones that produce reserve cells is reduced with age. Thus, satellite cell depletion with age could be attributed to a reduced capacity to generate a reserve population.

β-Hydroxy-β-Methylbutyrate Did Not Enhance High Intensity Resistance Training-Induced Improvements in Myofiber Dimensions and Myogenic Capacity in Aged Female Rats

“…Activated satellite cells may then proliferate nominally to repair small localized damage, fuse together to form myofibers in the face of considerable muscle injury, or provide additional nuclei to support myofiber expansion (Adams, 2006;Kook et al, 2006;Le Grand and Rudnicki, 2007). Because reduced basal satellite cell numbers have been observed in aged skeletal muscle (Day et al, 2010;Shefer et al, 2006;, the ability to undergo the regenerative process during senescence may be delayed and/or impaired, possibly contributing to muscle loss.…”

Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol

“…An explanation for a blunted myofiber hypertrophy in aged muscle may thus be a lower number, a decreased mechanosensitivity, impaired proliferation and/or differentiation of SCs. Here we found that the SC density was lower in old than adult muscle, which is in accordance with others (Day et al, 2010). Despite the agerelated reduction in SC density, overload did induce SC proliferation not only in adult, but also in old muscles.…”

Biological characteristics of muscle-derived satellite cells isolated from rats at different postnatal days

“…One method to solve this important problem in tissue engineering is to transplant a large number of cells after attachment to a scaffold material, however, this approach requires a rich source of cells. In previous studies, the research materials have been limited to skeletal muscle tissue harvested from rats within 10 days of birth (Day et al 2010). This study demonstrates that MDSCs can be isolated from the skeletal muscle tissue of rats up to 3 weeks after birth, thus expanding the source material for MDSCs.…”

“…In this study, we abandoned the long held idea that MDSCs can only be isolated from rat skeletal muscle within 10 days after birth (Day et al 2010). We explored the in vitro growth, proliferation and differentiation capacity of MDSCs isolated from rat skeletal muscle up to 42 days after birth, in order to provide a more substantial basis to identify whether MDSCs are ideal seed cells for regenerative medicine and explore their clinical applications.…”