Journal
STEM CELLS
Volume 33, Issue 8, Pages 2456-2468Publisher
WILEY
DOI: 10.1002/stem.2045
Keywords
Aging; Skeletal muscle; Regeneration; Pro-insulin-like growth factor-II
Categories
Funding
- JSPS KAKENHI [18890246, 20790242]
- National Center for Geriatrics and Gerontology (NCGG), Japan
- Grants-in-Aid for Scientific Research [15K12675, 26462701, 20790242, 18890246] Funding Source: KAKEN
Ask authors/readers for more resources
Sarcopenia, age-related muscle weakness, increases the frequency of falls and fractures in elderly people, which can trigger severe muscle injury. Rapid and successful recovery from muscle injury is essential not to cause further frailty and loss of independence. In fact, we showed insufficient muscle regeneration in aged mice. Although the number of satellite cells, muscle stem cells, decreases with age, the remaining satellite cells maintain the myogenic capacity equivalent to young mice. Transplantation of young green fluorescent protein (GFP)-Tg mice-derived satellite cells into young and aged mice revealed that age-related deterioration of the muscle environment contributes to the decline in regenerative capacity of satellite cells. Thus, extrinsic changes rather than intrinsic changes in satellite cells appear to be a major determinant of inefficient muscle regeneration with age. Comprehensive protein expression analysis identified a decrease in insulin-like growth factor-II (IGF-II) level in regenerating muscle of aged mice. We found that pro- and big-IGF-II but not mature IGF-II specifically express during muscle regeneration and the expressions are not only delayed but also decreased in absolute quantity with age. Supplementation of pro-IGF-II in aged mice ameliorated the inefficient regenerative response by promoting proliferation of satellite cells, angiogenesis, and suppressing adipogenic differentiation of platelet derived growth factor receptor (PDGFR)alpha(+) mesenchymal progenitors. We further revealed that pro-IGF-II but not mature IGF-II specifically inhibits the pathological adipogenesis of PDGFR alpha(+) cells. Together, these results uncovered a distinctive pro-IGF-II-mediated self-reinforcement mechanism of muscle regeneration and suggest that supplementation of pro-IGF-II could be one of the most effective therapeutic approaches for muscle injury in elderly people.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available