Aging-related learning and memory decline are hallmarks of aging and pose a significant health burden. The effects of walnut oligopeptides (WOPs) on learning and memory were evaluated in this study. Sixty SAMP8 mice were randomly divided into four groups (15 mice/group), including one SAMP8 age-control group and three WOP-treated groups. SAMR1 mice (n = 15) that show a normal senescence rate were used as controls. The SAMP8 and SAMR1 controls were administered ordinary sterilized water, while the WOP-intervention groups were administered 110, 220, and 440 mg/kg·bw of WOPs in water, respectively. The whole intervention period was six months. The remaining 15 SAMP8 (4-month-old) mice were used as the young control group. The results showed that WOPs significantly improved the decline in aging-related learning/memory ability. WOPs significantly increased the expression of BDNF and PSD95 and decreased the level of APP and Aβ1-42 in the brain. The mechanism of action may be related to an increase in the activity of antioxidant enzymes (SOD and GSH-Px), a reduction in the expression of inflammatory factors (TNF-α and IL-1β) in the brain and a reduction in oxidative stress injury (MDA). Furthermore, the expression of AMPK, SIRT-1, and PGC-1α was upregulated and the mitochondrial DNA content was increased in brain. These results indicated that WOPs improved aging-related learning and memory impairment. WOP supplementation may be a potential and effective method for the elderly.
Keywords: SAMP8; learning and memory; mitochondrial function; walnut oligopeptide.