The age-related changes in skeletal muscle cell populations and molecular profiles exhibit distinct patterns based on the levels of physical activity and fitness in individuals. Research has shown that individuals with higher levels of physical activity and fitness tend to have a more preserved muscle mass and function compared to sedentary individuals. In active and fit individuals, there is a tendency for a slower decline in muscle cell populations, such as satellite cells responsible for muscle repair and regeneration, compared to their sedentary counterparts. Additionally, physically active individuals often exhibit a more favorable molecular profile in their skeletal muscle, characterized by lower levels of inflammation, oxidative stress, and mitochondrial dysfunction, which are common features associated with sarcopenia and frailty in older adults. These individuals may also show enhanced expression of genes related to muscle growth, metabolism, and overall muscle health. On the other hand, sedentary individuals or those with lower fitness levels tend to experience a more rapid decline in muscle cell populations, increased inflammation, and altered gene expression patterns associated with muscle wasting and dysfunction. Therefore, the interplay between physical activity, fitness levels, and age-related changes in skeletal muscle highlights the importance of lifestyle factors in modulating the molecular and cellular processes underlying sarcopenia and frailty.