Reactive oxygen species (ROS) are closely related to the aging process. In our previous studies, we found that the saponins from Aralia taibaiensis have potent antioxidant activity, suggesting the potential protective activity on the aging. However, the protective effect of the saponins and the possible underlying molecular mechanism remain unknown. In the present study, we employed a D-galactose-induced aging rat model to investigate the protective effect of the saponins. We found that D-galactose treatment induced obvious aging-related changes such as the decreased thymus and spleen coefficients, the increased advanced glycation end products (AGEs) level, senescence-associated β-galactosidase (SAβ-gal) activity, and malondialdehyde (MDA) level. Further results showed that Forkhead box O3a (FOXO3a), nuclear factor-erythroid 2-related factor 2 (Nrf2), and their targeted antioxidants such as superoxide dismutase 2 (SOD2), catalase (CAT), glutathione reductase (GR), glutathione (GSH), glutamate-cysteine ligase (GCL), and heme oxygenase 1 (HO-1) were all inhibited in the aging rats induced by D-galactose treatment. Saponins supplementation showed effective protection on these changes. These results demonstrate that saponins from Aralia taibaiensis attenuate the D-galactose-induced rat aging. By activating FOXO3a and Nrf2 pathways, saponins increase their downstream multiple antioxidants expression and function, at least in part contributing to the protection on the D-galactose-induced aging in rats. 1. Introduction Aging is a biological process characterized by a progressive deterioration in physiological functions and metabolic processes that leads to morbidity and mortality. Numerous studies have shown that reactive oxygen species (ROS) play a critical role in the aging process since the free radical theory was first proposed by Harman in 1956 [1–4]. Even though there are contradictory reports whether or not increasing antioxidant capacity should increase organismal life span, it is recognized that increasing antioxidant capacity may at least attenuate the degree of aging and the related oxidative damages. ROS are O2-derived active free radicals, such as superoxide anion ( ), hydroxyl (HO？), peroxyl ( ), and alkoxyl (RO？) radicals, as well as nonradical species such as hydrogen peroxide (H2O2). Physiological levels of ROS are appreciated to function as signaling molecules to regulate a wide variety of physiology (e.g., signal transduction, gene expression, and redox regulation) [5], while high levels of ROS induce oxidative stress. The persistent
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