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

Area of Science:

• Cellular senescence and aging research.
• Molecular mechanisms of aging.
• Pharmacological interventions for aging.

Background:

• Oleanolic acid (OA) possesses known anti-inflammatory properties.
• The role of OA in aging processes remains largely uncharacterized.
• Insulin-like growth factor-1 (IGF-1) signaling is implicated in aging, but its regulatory mechanisms require further elucidation.

Purpose of the Study:

• To investigate the potential of oleanolic acid (OA) in delaying cellular aging.
• To elucidate the regulatory mechanism of OA on the PI3K/AKT/mTOR pathway.
• To examine the interaction between OA and insulin-like growth factor-1 (IGF-1) signaling in the context of aging.

Main Methods:

• Establishment of replicative and bleomycin-induced aging models in human and mouse fibroblasts.
• Treatment of aged cells with OA, IGF-1 inhibitors, or IGF-1 recombinant proteins.
• Assessment of aging markers including p16, IL-1β, IL-6, IL-8, and SA-β-gal staining.
• Quantification of protein and gene expression using Western blot, RT-qPCR, and ELISA.

Main Results:

• Senescent cells exhibited elevated levels of IGF-1, PI3K/AKT/mTOR pathway components, p16, and senescence-associated secretory phenotype (SASP) factors (IL-1β, IL-6, IL-8).
• Treatment with OA significantly reduced the expression of IGF-1, PI3K/AKT/mTOR, p16, and SASP factors in aged cells.
• OA treatment demonstrated a decrease in senescence markers.

Conclusions:

• Oleanolic acid (OA) effectively slows down cellular aging.
• OA exerts its anti-aging effects by inhibiting the PI3K/AKT/mTOR pathway through modulation of IGF-1.
• These findings position OA as a promising therapeutic agent for anti-aging strategies.