Age-dependent effects of a high-fat diet combined with dietary advanced glycation end products on cognitive function and protection with voluntary exercise.

To determine whether a high fat diet (HFD) combined with an advanced glycation end products (AGEs) diet will induce worse cognitive impairment than a HFD alone and to investigate whether voluntary exercise is capable of improving cognitive function after the combined diet, young and middle-aged male C57BL/6J mice were randomly assigned to four groups, i.e. , control, HFD, combined diet, and combined diet treated with voluntary exercise. Compared to HFD, combined diet induced worse memory abilities only in middle-aged mice, as exhibited by the reduced number of crossings and reduced distance in the target zone during a probe trial. Exercise reversed combined-diet-induced cognitive impairment for both ages of mice. For young mice, the neuro-protective effects of exercise were mainly associated with inhibition of NLRP3, Dnmt3a, Dnmt3b, and H3K9me2 and elevation of OST48; it also elevated Bacilli and reduced Epsilonproteobacteria , Campylobacterales , and Helicobacter . For middle-aged mice, exercise elevated Tet2, inhibited NF-κB and NLRP3, and rebalanced circadian clock proteins and the RAGE-OST48 axis; also, exercise elevated Coriobacteriia / Coriobacteriaceae , Erysipelotrichaceae , and Allobaculum and restored intestinal permeability.