Muscle stem cell function is impaired during aging
Julia von Maltzahn
Skeletal muscle has diverse functions in the organism including voluntary locomotion, postural behaviour as well as breathing. Muscle tissue exhibits a remarkable ability to adapt to physiological demands such as growth, training and injury. Regeneration of skeletal muscle after injury is dependent on muscle stem cells, also termed satellite cells. During aging the regenerative capacity of skeletal muscle declines concomitant with a decrease in number and functionality of muscle stem cells. Both, systemic and tissue intrinsic factors contribute to the age-associated decline in the regenerative capacity of skeletal muscle. Aging-dependent intrinsic changes in muscle stem cells include changes in JAK/STAT signaling or Hoxa9 expression. But also the extracellular matrix demonstrates aging-dependent changes, e.g. age-dependent changes in the expression of the extracellular matrix protein fibronectin is affecting the regenerative capacity of aged skeletal muscle and muscle stem cell function. Klotho is a well-known anti-aging hormone, which serves as a suppressor of aging through a variety of mechanisms. Klotho signaling also plays an
important role for muscle stem cell function and regeneration of skeletal muscle. Loss of klotho expression severely impairs regeneration of skeletal muscle and impairs muscle stem cell function while addition of recombinant klotho protein improves muscle stem function in the aged. Klotho is presumably counteracting aberrant excessive canonical Wnt signaling in aged muscle stem cells, it might be one of the naturally occurring inhibitors of canonical Wnt signaling in skeletal muscle.
Skeletal muscle has diverse functions in the organism including voluntary locomotion, postural behaviour as well as breathing. Muscle tissue exhibits a remarkable ability to adapt to physiological demands such as growth, training and injury. Regeneration of skeletal muscle after injury is dependent on muscle stem cells, also termed satellite cells. During aging the regenerative capacity of skeletal muscle declines concomitant with a decrease in number and functionality of muscle stem cells. Both, systemic and tissue intrinsic factors contribute to the age-associated decline in the regenerative capacity of skeletal muscle. Aging-dependent intrinsic changes in muscle stem cells include changes in JAK/STAT signaling or Hoxa9 expression. But also the extracellular matrix demonstrates aging-dependent changes, e.g. age-dependent changes in the expression of the extracellular matrix protein fibronectin is affecting the regenerative capacity of aged skeletal muscle and muscle stem cell function. Klotho is a well-known anti-aging hormone, which serves as a suppressor of aging through a variety of mechanisms. Klotho signaling also plays an
important role for muscle stem cell function and regeneration of skeletal muscle. Loss of klotho expression severely impairs regeneration of skeletal muscle and impairs muscle stem cell function while addition of recombinant klotho protein improves muscle stem function in the aged. Klotho is presumably counteracting aberrant excessive canonical Wnt signaling in aged muscle stem cells, it might be one of the naturally occurring inhibitors of canonical Wnt signaling in skeletal muscle.
