Background and Objective: Soy lecithin(SL) have beneficial effects on many chronic diseases including age-associated neurodegenerative disease and sarcopenia. However, the specific mechanisms and regulation targets are unclear. In this study, we investigated the effects of SL on learning and memory impairment and muscle attenuation in SAMP8 mice. Meanwhile, we explored the regulatory mechanism of FNDC5/irisin in muscle-brain crosstalk. Methods: SAMP8 mice were randomly divided into 3 groups: model(M) group, 200 mg/kg·d soy lecithin(200-SL) group, 100 mg/kg·d soy lecithin(100-ChromatographySL) group. SAMR1 were as the control group. The mice in M and control groups were treated with 0.5% CMC-Na, and other groups were provided SL by daily intragastric administration for 8 weeks. Morris water maze test was used to evaluate the cognitive decline. Grip strength and rotarod tests were used to evaluate the attenuation of muscle. The activity of superoxide dismutase(SOD) and malondialdehyde(MDA) content in brain were measured to assess the physiological changes. Moreover, mRNA andRAD001体内/or protein expressions of FNDC5/irisin was gauged. Results: In behavior test, compare with M group, the latency of Morris water maze test of 200-SL group and 100-SL group were significantly reduced, while number of crossing the platform and time in target quadrant were increased. Mice in 200-SL and 100-SL group had greater grip strength and the latency for the mice to fall from the rod were increased. Meanwhile, the improvement of 200-SL group was better than that of 100-SL group(P < 0.05). Similar trend was observed in physiological changes. The MDA level was effectively decreased and the SOD activity increased in hippocampus of SL groups(P < 0.05). Besides we got the phenomenon that soy lecithin could upregulate the mRNA and protein expressions of FNDC5/irisin in brain. Conclusion: Soy lecithin could alleviate the impairment in learning and memory and motor coordination in SAMP8 through regulating C59体外FNDC5/irisin pathway.