Skeletal muscle aerobic capacity, mitochondrial function and regenerative capacity have been found to decline with age in humans and rodents. However, not much is known about age-related changes in mitochondrial function in equine skeletal muscle. The objectives of this dissertation were to: 1) evaluate differences in skeletal muscle mitochondrial function between young and aged horses; 2) address underlying mechanisms for the age-related alterations in mitochondrial function; and 3) examine differences in the intrinsic regenerative capacity of muscle stem cells isolated from skeletal muscle of young and aged horses.

We first compared muscle aerobic capacity, especially mitochodnrial density and function in gluteus medius (GLU) and triceps brachii (TRI) muscle between young and aged American Quarter Horses. Equine skeletal muscle aging was accompanied by a shift in fiber type composition towards a higher percentage of type I and IIA muscle fibers, decrease in mitochondrial density and cytochrome c oxidase activity, but preserved mitochodnrial respiratory function.

To further understand the underlying cause for the age-associated decrement of mitochondrial density and function in equine skeletal muscle, expression of factors involved in mitochondrial biogenesis and mitochondrial-selective autophagy pathways, two of the most prominent quality control mechanisms that have been described, were analyzed. Our data suggest that mitochondrial content and biogenesis markers were reduced in aged-TRI, and that autophagic activity was impaired in both muscles with age, albeit more pronounced in the TRI muscle.

Myogenic stem cells, commonly referred to as satellite cells, are responsible for muscle growth and repair after birth. However, the ability to regenerate muscle and replace damaged myofibers declines with age. We then asked whether the intrinsic changes within an aged satellite cell would cause alteration in regenerative capacity in equines. In vitro studies with primary satellite cell cultures under standard conditions suggest that satellite cells isolated from aged horses displayed compromised proliferative, differentiation and fusion capacity in vitro. In line with compromised myogenic potential of aged muscle-derived satellite cells, there were age-related alterations in mitochondrial biogenesis and autophagy pathways, with satellite cells derived from TRI muscle being more susceptible to impairments with age.