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Muscle-aging drives sarcopenia and is a major public health issue. Mice are frequently used as a model for human muscle-aging, however, research investigating their translational value is limited. In addition, mechanisms underlying muscle-aging may have sex-specific features in humans, but it is not yet assessed whether these are recapitulated in mice.
Here, we studied the effects of aging on a functional, histological and transcriptional level at multiple timepoints in male and female mice 4, 17, 21 and 25 months , with particular emphasis on sex-differences. The effects of natural aging on the transcriptome of quadriceps muscle were compared to humans on pathway level.
In male, but not female mice, major distinctive aging-related changes occurred in the last age group 25 months , which highlights the necessity for careful selection of age using mice as a muscle-aging model. Furthermore, contrasting to humans, more aging-related changes were found in the muscle transcriptome of male mice compared to female mice vs.
Subsequently, male mice recapitulated more muscle-aging related pathways characteristic for both male and female humans. In conclusion, our data show that sex has a critical effect on the mouse muscle-aging trajectory, although these do not necessarily reflect sex differences observed in the human muscle-aging trajectory. Sarcopenia is an aging related disease characterized by loss of muscle strength and mass [ 1 , 2 ] and increases the risk for frailty and mortality in the older population [ 3 , 4 ].
