During muscle ageing the activation of the mitogenic signalling is not sufficient to guarantee cellular duplication.
Satellite cells are quiescent cells that can be induced to proliferate by a variety of stimuli such as injury and exercise, providing in this way a source of new myoblasts that repopulate the damaged muscle. It is well known that, as senescence progresses, the muscle regenerative potential progressively diminishes, but the molecular mechanisms underlying this process are not yet completely defined. Many growth factors, including Platelet Derived Growth Factor (PDGF-BB)*, have been associated to satellite cells activation, acting as potent mitogenic agents for these cells. The aim of this study is to explore if the diminished response of senescent myoblasts to growth stimuli could be due to the inability to receive and transduce hormonal signals. Herein, we demonstrate that that although PDGF-r expression is down-regulated during senescence, the receptor is fully able to be phosphorylated and to transmit the signal. Although senescent myoblasts display increased level of phosphotyrosine phosphatases (PTPs), neither the PDGF receptor (PDGF-r) phosphorylation level nor the citosolic signal transduction machinery is affected. Indeed, we demonstrated that senescent human myoblasts are able to initiate a proper mitogenic signalling cascade, since the activation of mitogen-activated protein kinases (MAPK) and phosphatydil inositole 3 kinase (PI-3K) pathways is similar in young and senescent cells. Our data underline that, despite a conserved capability to activate PDGF-r after agonist stimulation and a functional signal transduction machinery, the mitogenic signal initiated by growth factors in senescent cells does not lead to cell division, being unable to overcome the cell cycle block, likely caused by the accumulation of the inhibitor p21WAF1.
Buricchi
Francesca
F
Dipartimento di Scienze Biochimiche, Università di Firenze, viale Morgagni 50, 50134 Firenze, Italia.
Chiarugi
Paola
P
Fiaschi
Tania
T
Giannoni
Elisa
E
Magnelli
Lucia
L
Fanti
Elena
E
Raugei
Giovanni
G
Ramponi
Giampietro
G