c-Flip overexpression affects satellite cell proliferation and promotes skeletal muscle aging

Abstract

This study shows that forcing c-Flip overexpression in undifferentiated skeletal myogenic cells in vivo results in early aging muscle phenotype. In the transgenic mice, adult muscle histology, histochemistry and biochemistry show strong alterations: reduction of fibers size and muscle mass, mitochondrial abnormalities, increase in protein oxidation and apoptosis markers and reduced AKT/GSK3β phosphorylation. In the infant, higher levels of Pax-7, PCNA, P-ERK and active-caspase-3 were observed, indicating enhanced proliferation and concomitant apoptosis of myogenic precursors. Increased proliferation correlated with NF-κB activation, detected as p65 phosphorylation, and with high levels of embryonic myosin heavy chain. Reduced regenerative potential after muscle damage in the adult and impaired fiber growth associated with reduced NFATc2 activation in the infant were also observed, indicating that the satellite cell pool is prematurely compromised. Altogether, these data show a role for c-Flip in modulating skeletal muscle phenotype by affecting the proliferative potential of undifferentiated cells. This finding indicates a novel additional mechanism through which c-Flip might possibly control tissue remodeling.

Effect of green tea on aged rat skeletal muscle

“…These observations were in agreement with previous conclusions that a decrease in the synthesis of myofibrillar proteins occurs in elderly compared with young individuals [28]. Similar mitochondrial changes were observed [29]. This theory is in agreement with previous studies [28] that have reported alterations in protein metabolism in old muscles.…”

Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration

“…In many tissues, most notably skeletal muscle, liver, and kidneys, the age-related decline of regenerative potential is correlated with the loss of stem or progenitor cells via necrotic or apoptotic cell death (Collins et al, 2007; Giampietri et al, 2010; Menthena et al, 2011; Suzuki et al, 2012; Yang et al, 2010). In the case of the cochlea, such cell death may also be playing a role.…”

TNF-αand IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-StimulatedAtrogin1andMuRF1Genes in C2C12 Myotubes

“…NF- κ B regulates the expression of a variety of muscle genes and proteins including those involved in control of cell proliferation [34], myogenesis, oxidative stress, and mitochondrial dysfunction [35]. Thus, higher NF- κ B activity observed after TNF- α administration in this experiment suggests that differentiating myoblasts could be withdrawn from the myogenic program as shown recently in muscle-derived stem cells isolated from transgenic mice [36], or by enforced expression of c-FLIP in satellite cells [37]. Moreover, c-FLIP is a known intracellular modulator of death receptor mediated signaling (inhibition of intrinsic apoptosis) and NF- κ B activator [38].…”