Increased Adipocyte Area in Injured Muscle With Aging and Impaired Remodeling in Female Mice.
We demonstrated that young male and female mice similarly regenerated injured skeletal muscle; however, female mice transiently increased adipocyte area within regenerated muscle in a sex hormone-dependent manner. We extended these observations to investigate the effect of aging and sex on sarcopenia and muscle regeneration. Cardiotoxin injury to the tibialis anterior muscle of young, middle, and old-aged C57Bl/6J male and female mice was used to measure regenerated myofiber cross-sectional area (CSA), adipocyte area, residual necrosis, and inflammatory cell recruitment. Baseline (uninjured) myofiber CSA was decreased in old mice of both sexes compared to young and middle-aged mice. Regenerated CSA was similar in male mice in all age groups until baseline CSA was attained but decreased in middle and old age female mice compared to young females. Furthermore, adipocyte area within regenerated muscle was transiently increased in young females compared to young males and these sex-dependent increases persisted in middle and old age female mice and were associated with increased Pparg Young female mice had more pro-inflammatory monocytes/macrophages in regenerating muscle than young male mice and increased Sca-1(+)CD45(-)cells. In conclusion, sex and age influence pro-inflammatory cell recruitment, muscle regeneration, and adipocyte area following skeletal muscle injury.
Department of Surgery.
Caitlin M
CM
Fearing
Department of Surgery, Department of Cellular and Structural Biology, Sam and Ann Barshop Institute for Longevity and Aging Studies.
David W
DW
Melton
Department of Surgery.
Xiufen
X
Lei
Department of Surgery.
Heather
H
Hancock
Department of Surgery.
Hanzhou
H
Wang
Department of Surgery.
Zaheer U
ZU
Sarwar
Department of Surgery.
Laurel
L
Porter
Department of Surgery.
Matthew
M
McHale
Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Pathology, and Department of Periodontics, University of Texas Health Science Center, San Antonio.
Linda M
LM
McManus
Department of Surgery, Sam and Ann Barshop Institute for Longevity and Aging Studies, The South Texas Veterans Health Care System, San Antonio. shireman@uthscsa.edu.
Paula K
PK
Shireman
D017667:Adipocytes / Q000187:drug effects*; D000375:Aging; D000818:Animals; D054715:Cardiotoxins / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology*; D012038:Regeneration; D055948:Sarcopenia / Q000473:pathology*; D012727:Sex Characteristics
D054715:Cardiotoxins
Monocyte/macrophage; Muscle regeneration; Sarcopenia