Intracellular Protons Accelerate Aging and Activate Aging Hallmarks in Mice

The study investigated the effects of intracellular acidosis on aging in mice by analyzing coupling factor 6-overexpressing transgenic (TG) and high salt-fed mice, both of which exhibited sustained intracellular acidosis. These mice showed shortened lifespans and early aging signs such as hair greying, alopecia, weight loss, and reduced organ mass. The research found that chronic intracellular acidosis impaired autophagy through the regression of Atg7 and increased acetylation of autophagy-related proteins. Additionally, significant changes in histone methylation and reductions in nuclear structural proteins were observed. These findings highlighted a novel mechanism of aging and impaired autophagy, suggesting potential targets for anti-aging therapies.