The senescence and senescence-related secretory phenotypes of muscle cells or stem cells lead to defects in muscle regeneration in the elderly. This phenomenon causes senile sarcopenia, cachexia and increases disease mortality. We performed cDNA arrays to study aging human myoblasts (HSMM) and found that the expression of transferrin receptor 1 and ferritin (Ft) increased. The significant increase in ferritin led to a decrease in free iron-dependent oxidative damage in cells, which is related to the anti-death properties of senescent cells. Iron-dependent apoptosis (ferroptosis) is a new form of programmed cell death in which the accumulation of free iron in cells promotes lipid peroxidation. Therefore, in this proposal, we specifically reduced the senescent cells to change the aging microenvironment via manipulating the iron storage or transport out of cells. The results show that in radiation-induced senescent HSMM or mouse quadriceps muscle cells, Ft shRNA effectively inhibited the expression of ferritin, thereby eliminating senescence-related p16 and -galactosidase activity and increasing myogenesis. The conditioned medium of HSMM with Ft shRNA transduction also reduced the senescence of normal HSMM, it indicated that Ft shRNA transduction ameliorate the aging niche. These results show that specifically enhancing ferroptosis in senescent myoblast or myocytes to change the aging microenvironment effectively improves aging-related muscle regeneration defects.
|Effective start/end date
|2020/08/01 → 2021/07/31
- muscle regeneration
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