Oleanolic Acid Slows Down Aging Through IGF-1 Affecting the PI3K/AKT/mTOR Signaling Pathway

A pentacyclic triterpene, oleanolic acid (OA), has anti-inflammatory activity. The role of oleanolic acid in aging is poorly understood, and the regulatory mechanism of IGF-1 signaling in aging is still not fully understood. Thus, we hypothesized that OA could delay aging by regulating the PI3K/AKT/mTOR pathway via insulin-like growth factor-1 (IGF-1). This study initially established a replicative aging model and a bleomycin-induced aging model in human dermal fibroblast (HDF) and mouse embryonic fibroblast (MEF) cell lines. On this basis, IGF-1 inhibitors or IGF-1 recombinant proteins were then combined with OA (at a concentration of 20 μM) and treated for 72 h. The project plans to detect the expression of aging-related proteins such as CDKN2A (p16) using Western blot technology, detect the expression of aging-related factors such as Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), Enzyme-Linked Immunosorbent Assay (ELISA), and other technologies, and combine Senescence-Associated β-Galactosidase (SA-β-gal) staining to detect changes in aging. The expression of IGF-1, PI3K/AKT/mTOR, aging-related proteins P16, and aging-related secretory factors (SASP) IL-1β, IL-6, and IL-8 was increased in senescent cells. After treatment with jujuboside, the expression of IGF-1, PI3K/AKT/mTOR, aging-related protein P16, and aging-related secretory factors IL-1β, IL-6, and IL-8 were decreased. The findings suggested that OA slowed down aging by inhibiting the PI3K/AKT/mTOR expression through IGF-1. These findings suggest OA as a potential new drug and its mechanisms for anti-aging.