The accumulation of damaged proteins can perturb cellular homeostasis and provoke aging, pathological states and cell death. Quality control systems, such as the unfolded protein response (UPR), inflammasome and autophagy, mitigate the residence time of damaged proteins. In the present study, we have examined the UPR and inflammasome in the liver of young (Y; ~ 5 mo.) and old (O, ~29 mo.) mice (n=8/group) and the ability of trehalose, a compound linked to increased protein stability and autophagy, to counteract aging‐induced effects on these systems. When used, trehalose was provided for 4 wks in the drinking water (n=7/group). Livers from O mice were characterized by activation of the UPR and inflammasome and increased indices of liver injury. Mitofusin‐2 (Mfn‐2), a protein linked to protection against endoplasmic reticulum stress and UPR activation, was reduced in O vs. Y. Trehalose treatment reduced the activation of the UPR and inflammasome, and restored Mfn‐2 in O mice. It has been postulated that a collapse of proteostasis promotes many age‐associated pathologies. Trehalose appears to be an effective intervention to mitigate the activation of quality control systems that respond to disruption of proteostasis in the liver. We postulate that the age‐associated reduction in Mfn‐2 is critical to the activation of the UPR and inflammasome in the liver of old mice.Grant Funding Source: NIH DK072017, AG013038, AG039210