Aged Mice Lacking Fatty Acid Amide Hydrolase Show Reduced Neuroinflammation, Senescence, and Cognitive Impairment

The relationship between lipid-derived messengers and inflammation is a promising avenue for therapeutics in a number of diseases. The enzyme, Fatty Acid Amide Hydrolase (FAAH), has been implicated as an effective treatment point for afflictions such as pain, however, its involvement in the regulation of endogenous lipids involved in the inflammatory response in the central nervous system (CNS) has not yet been explored in great depth. Here, I demonstrate that aged mice lacking FAAH show not only a significantly reduced inflammatory profile (Il-1ß, Il-6, TNF-α, iNOS), within the CNS but also reduced incidence of glial fibrosis (GFAP), cellular senescence (p21, p53), decreased ceramide levels (d18:1/24:1) and improved learning and memory in the Object Location Memory Paradigm. The results suggest that inhibition of FAAH in aged mice is able to reverse the effects of neuroinflammation and perhaps lead to more ‘successful’ aging in these animals