Dual role of the caspase enzymes in satellite cells from aged and young subjects

Abstract

Satellite cell (SC) proliferation and differentiation have critical roles in skeletal muscle recovery after injury and adaptation in response to hypertrophic stimuli. Normal ageing hinders SC proliferation and differentiation, and is associated with increased expression of a number of pro-apoptotic factors in skeletal muscle. In light of previous studies that have demonstrated age-related altered expression of genes involved in SC antioxidant and repair activity, this investigation was aimed at evaluating the incidence of apoptotic features in human SCs. Primary cells were obtained from vastus lateralis of nine young (27.3±2.0 years old) and nine old (71.1±1.8 years old) subjects, and cultured in complete medium for analyses at 4, 24, 48, and 72 h. Apoptosis was assessed using AnnexinV/propidium iodide staining, the terminal deoxynucleotidyl transferase dUTP nick-end labelling technique, RT-PCR, DNA microarrays, flow cytometry, and immunofluorescence analysis. There was an increased rate of apoptotic cells in aged subjects at all of the experimental time points, with no direct correlation between AnnexinV-positive cells and caspase-8 activity. On the other hand, CASP2, CASP6, CASP7, and CASP9 and a number of cell death genes were upregulated in the aged SCs. Altogether, our data show age-related enhanced susceptibility of human SCs to apoptosis, which might be responsible for their reduced response to muscle damage.

Low‐load resistance exercise during inactivity is associated with greater fibre area and satellite cell expression in older skeletal muscle

“…Mechanistically, the factors responsible for the loss of SC with inactivity are not defined but may be related to cell apoptosis. For example, SC isolated from aged muscle display greater rates of apoptosis concomitant with rises in caspase family members and cell death genes . In contrast, resistance exercise can induce an expansion of the SC pool in older skeletal muscle despite a delayed type II fibre‐associated SC response .…”

Programmed Cell Death Genes Are Linked to Elevated Creatine Kinase Levels in Unhealthy Male Nonagenarians

“…A similar apoptotic tendency is also seen in adult stem cells. Satellite cells, which are myogenic stem cells important for skeletal muscle regeneration, from old subjects (mean age = 71 years) are more prone to apoptotic cell death, compared with those from young subjects (mean age = 27 years) [60]. The cell death genes upregulated in the satellite cells from old subjects include the caspase 9 gene, whose activation is promoted by cytochrome c [61].…”

Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts

“…High levels of ROS are associated with metabolic diseases like diabetes [16,20,36], which may contribute to the loss of myoblast function, increase myoblast cell death [33] and further exacerbate muscle repair in aging. Fulle and colleagues [25] have demonstrated that a high percentage of the myogenic precursor cells from elderly muscles undergo apoptosis triggered by mitochondrial-associated caspase-9 and this appears to be closely linked to the high ROS levels that are found in aged muscles [20]. Thus, we predict that strategies to attenuate high ROS levels should reduce apoptosis in myoblasts and improve muscle differentiation/repair in aging and in other diseases that have elevated ROS levels.…”