Hydrogen Sulfide Upregulates Autophagy in Muscle Tissue
An increase in hydrogen sulfide in tissues has been shown to modestly slow aging in mice, acting on some of the well-studied beneficial pathways and cellular maintenance mechanisms triggered by mild stresses. Here, researchers show that hydrogen sulfide upregulates autophagy in muscle tissue, making it one of many interventions that slow aging via this mechanism. The practice of calorie restriction appears to extend life in short-lived laboratory species largely via improved autophagy, but calorie restriction does not radically extend life in long-lived mammals. Calorie restricted mice may exhibit as much as a 40% longer life span, but calorie restricted humans certainly do not. As a result, researchers do not expect that any other autophagy-based approach will do much to extend human life span.
As individuals age, there is a concomitant decline in the number of muscle fibres and the cross-sectional area of muscle. The decline in mass and function of skeletal muscle in older adults often results in falls, disability and even death. Hydrogen sulfide (H2S) is a gasotransmitter that is produced endogenously in mammals, primarily through enzymatic pathways. H2S directly reacts with oxygen, hydrogen peroxide, and peroxynitrite, thereby reducing cellular oxidative damage. Additionally, it can modify proteins post-translationally through S-sulfhydration, which affects their functionality. Studies have demonstrated that human skeletal muscle expresses a considerable number of H2S-producing enzymes.
H2S has been shown to effectively alleviate muscle atrophy caused by diabetes and obesity. The precise mechanism by which this occurs is not yet fully understood. However, scientists have postulated that it may be related to H2S antioxidant stress, the regulation of mitochondrial energy metabolism, the reduction of apoptosis, and the up-regulation of autophagy. The objective of this study was to investigate whether H2S can enhance the expression and S-sulfhydration of USP5, thereby facilitating the deubiquitination of AMPKα1. Which, in turn, would result in the up-regulation of autophagy, which would contribute to the alleviation of skeletal muscle ageing. We find this to be the case.