INTRODUCTION
death, disability
PATHOLOGY, PROLIFERATIVE
Across animal species, aging is associated with typical anatomical and physiological changes in multiple tissues and organs, as well as with pathology and functional impairments; these eventually lead to disability and death (Blagosklonny & Hall, In previous studies in model organisms, CR positively affects skeletal muscle by improving satellite cell proliferative capacity (Cerletti et al., To date, the sparse information available in humans has been gathered in cross‐sectional studies or small, short‐term randomized studies. A comparison of muscle biopsies from individuals who had been following a CR diet voluntarily for several years versus age‐matched individuals on a Western diet showed that CR enhances proteostasis and cellular quality‐control processes (Yang et al., To shed light on mechanisms by which CR may improve muscle health, we performed a comprehensive high‐depth RNA sequencing (RNA‐Seq) analysis of skeletal muscle collected in a selected group for eligible study participants in CALERIE 2. Our aim was to explore gene expression and splicing variants changes induced by CR compared to AL group over 12 and 24‐month. We also aimed to investigate the impact of biological pathways and their mediation effect on CR on muscle quality, operationalized as mass‐adjusted muscle strength.