Arginase II Deficiency Slows Muscle Aging in Mice
Researchers here demonstrate that the increased level of arginase II observed with advancing age is causing some degree of issues, using mice from a lineage in which arginase II was removed by genetic engineering. Mice lacking arginase II exhibit slowed loss of muscle mass with age, and a lower burden of cellular senescence. Given what is known of arginase II, reduced cellular senescence and inflammatory signaling seem likely to be the important mediating mechanisms, but there are other possibilities to consider. Perhaps the more interesting point is that removing arginase II isn't evidently problematic, only beneficial.
Age-associated sarcopenia decreases mobility and is promoted by cell senescence, inflammation, and fibrosis. The mitochondrial enzyme arginase-II (Arg-II) plays a causal role in aging and age-associated diseases. Therefore, we aim to explore the role of Arg-II in age-associated decline of physical activity and skeletal muscle aging in a mouse model. Young (4-6 months) and old (20-24 months) wild-type (wt) mice and mice deficient in arg-ii (arg-ii-/-) of both sexes are investigated. We demonstrate a decreased physical performance of old wt mice, which is partially prevented in arg-ii-/- animals, particularly in males.
The improved phenotype of arg-ii-/- mice in aging is associated with reduced sarcopenia, cellular senescence, inflammation, and fibrosis, whereas age-associated decline of microvascular endothelial cell density, satellite cell numbers, and muscle fiber types in skeletal muscle is prevented in arg-ii-/- mice. Finally, we demonstrate an increased arg-ii gene expression level in aging skeletal muscle and found Arg-II protein expression in endothelial cells and fibroblasts, but not in skeletal muscle fibers, macrophages, and satellite cells. Our results suggest that increased Arg-II in non-skeletal muscle cells promotes age-associated sarcopenia, particularly in male mice.