%0 Journal Article
%T Mouse sarcopenia model reveals sex- and age-specific differences in phenotypic and molecular characteristics.
%A Kerr HL
%A Krumm K
%A Anderson B
%A Christiani A
%A Strait L
%A Li T
%A Irwin B
%A Jiang S
%A Rybachok A
%A Chen A
%A Dacek E
%A Caeiro L
%A Merrihew GE
%A MacDonald JW
%A Bammler TK
%A MacCoss MJ
%A Garcia JM
%J J Clin Invest
%V 134
%N 16
%D 2024 Jun 11
%M 39145448
%F 19.456
%R 10.1172/JCI172890
%X Our study was to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition to investigate the underlying molecular mechanisms. Aged male (23-32 months old) and female (27-28 months old) C57BL/6J mice were classified as non-, probable-, or sarcopenic based on assessments of grip strength, muscle mass, and treadmill running time, using 2 SDs below the mean of their young counterparts as cutoff points. A 9%-22% prevalence of sarcopenia was identified in 23-26 month-old male mice, with more severe age-related declines in muscle function than mass. Females aged 27-28 months showed fewer sarcopenic but more probable cases compared with the males. As sarcopenia progressed, a decrease in muscle contractility and a trend toward lower type IIB fiber size were observed in males. Mitochondrial biogenesis, oxidative capacity, and AMPK-autophagy signaling decreased as sarcopenia progressed in males, with pathways linked to mitochondrial metabolism positively correlated with muscle mass. No age- or sarcopenia-related changes were observed in mitochondrial biogenesis, OXPHOS complexes, AMPK signaling, mitophagy, or atrogenes in females. Our results highlight the different trajectories of age-related declines in muscle mass and function, providing insights into sex-dependent molecular changes associated with sarcopenia progression, which may inform the future development of novel therapeutic interventions.