Senescence-associated frailty and sarcopenia are global challenges. We here investigated neuronal activity and skeletal muscle biology in senescence-accelerated mouse prone 8 (SAMP8) mice with scalp acupuncture stimulation (SAPS). Excise activity was assessed using rotarod test in the three groups: SAMP8 mice receiving SAPS (SP8-Ap), SAMP8 controls (SP8-C), and senescence-accelerated mouse resistant 1 controls (SR1). SP8-Ap exhibited significantly improved exercise activity compared to SP8-C. SAPS increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the frontal cortex of SP8-Ap. Monocyte/macrophage infiltration was significantly reduced in the gastrocnemius of SP8-Ap mice, which was associated with reduced expression of various glycogen synthase kinase-3β (GSK3β)-mediated inflammatory genes and increased insulin-like growth factor (IGF)-1 mRNA and phosphorylated AKT. These results indicate that elevation of neurotropic factors in the frontal cortex by SAPS can improve the exercise activity and skeletal muscle status. SAPS may represent a novel therapeutic approach to improve senescence-related frailty.