Brain aging plays a pivotal role in senescence process and is related to cognition impairments and memory deficit and increases the risk of neurological disorders, but ideal therapeutic intervention has not been found. Here we report a dramatic effect of acupuncture, a powerful non-drug therapy way, on preventing changes in gene expression profiles with aging in senescence-accelerated mouse (SAMP10). We show that 48 genes in 588 genes examined display 2-fold or greater changes in gene expression with aging. However, we find that acupuncture can completely or partially prevent expression alterations of almost all these genes induced by aging. Our findings highlight a role of acupuncture as a potential intervention in anti-aging process and clinical therapy in future.