Research Paper Volume 7, Issue 9 pp 718—733

Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells


Figure 10. A summary and comparison of the physiological characteristics (phenotypes) of the DN-p38αAF/+ and cMyc+/− hypomorphs. The physiological consequences of attenuation of p38α or cMyc signaling activities suggest that the levels of their signaling activities play a key role in the delay of progression of the aging phenotype. The model above suggests that the DN-p38AF/+ mice, through their attenuation of phosphorylation of IκκB may decrease the NFκB activation of cMYC thereby contributing to the delay of the aging phenotype attributed to the cMYC+/−hypomorph. The studies concerning these hypomorphs emphasize the attenuation of two critical physiological centers of distribution of signals that promote the progression of the aging phenotype, i.e., oxidative stress, inflammation, various juvenile protective factors and tumor suppressors. Both studies stress the importance of attenuation, not ablation, of the activities in the regulation (homeostasis) of these signaling distribution centers.