Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy

Abstract

To investigate the cause of skeletal muscle weakening during aging we examined the sequence of cellular changes in murine muscles. Satellite cells isolated from single muscle fibers terminally differentiate progressively less well with increasing age of donor. This change is detected before decline in satellite cell numbers and all histological changes examined here. In MSVski transgenic mice, which show type IIb fiber hypertrophy, initial muscle weakness is followed by muscle degeneration in the first year of life. This degeneration is accompanied by a spectrum of changes typical of normal muscle aging and a more marked decline in satellite cell differentiation efficiency. On a myoD-null genetic background, in which satellite cell differentiation is defective, the MSVski muscle phenotype is aggravated. This suggests that, on a wild-type genetic background, satellite cells are capable of repairing MSVski fibers and preserving muscle integrity in early life. We propose that decline in myogenic cell differentiation efficiency is an early event in aging-related loss of muscle function, both in normal aging and in some late-onset muscle degenerative conditions.

Lack of myostatin results in excessive muscle growth but impaired force generation

“…Overexpression of ski in MSVski transgenic mice resulted in Type IIb fiber hypertrophy accompanied by a 30% decrease in specific force generation (19). Ski negatively regulates Smad phosphorylation (20)(21)(22), thereby inhibiting signaling of TGF-␤-like factors, such as myostatin.…”

In vivo GDF3 administration abrogates aging related muscle regeneration delay following acute sterile injury

“…Aside from reduced numbers of satellite cells (Garcia‐Prat, Sousa‐Victor, & Munoz‐Canoves, 2013; Shefer, Mark, Richardson, & Yablonka‐Reuveni, 2006), the differentiation capacity of satellite cells is also reduced with aging. Moreover, the number of differentiating satellite cells is decreased in aged mice, as shown by downregulation of differentiation markers such as desmin and myogenin (Charge, Brack, & Hughes, 2002; Collins, Zammit, Ruiz, Morgan, & Partridge, 2007). In addition to satellite cells, there is clear evidence supporting the essential role of immune cells both in the clearance of damaged tissue and enhancing tissue regeneration upon injury (Tidball, 2017).…”

Prospectus of cultured meat—advancing meat alternatives

“…Atrophy and Exercise One of the potential problems associated with cultured meat is that of atrophy or muscle wasting due to a reduction of cell size (Fox 1996) caused by lack of use, denervation, or one of a variety of diseases (Charge et al 2002;Ohira et al 2002). Regular contraction is a necessity for skeletal muscle and promotes differentiation and healthy myofiber morphology while preventing atrophy.…”