Transcriptomic analysis demonstrates moderators of muscle quality are altered in age-related sarcopenic obesity

Sarcopenic obesity (SO) is the combined condition of sarcopenia and obesity, which commonly occurs in the older adult population. SO is associated with poor physical function, increased risk of musculoskeletal injury, and reduced quality of life and independence. Information on the molecular underpinnings of this condition is limited. The aim of this study was to provide a transcriptomic analysis characterizing SO induced by lifelong obesity and to provide a deeper understanding of the etiology of the condition.

Young (Y) (6 mo) and aged (A) (21-24 mo) mice were fed either normal chow (L) (12% kcal from fat) or high-fat (O) (60% kcal from fat) diets ad libitum. Through multiple analyses, we observed that genes related to ECM remodeling were downregulated in AO compared with YO, providing insight into the effects of age in a life-long obese condition. Furthermore, we observed that genes related to contraction in slow-twitch muscle fibers and fast-to-slow muscle fiber type transitions were upregulated with obesity in the aged condition.

Taken together, our findings reveal specific pathways of dysregulation in SO skeletal muscle, offering molecular insights that enhance our understanding of the underlying mechanisms contributing to impaired muscle function in this condition. Further exploration of these dysregulations is critical to identifying therapeutic treatments targeting the source of muscle functional impairment in SO.