Crosstalk Between Inflammation and Cellular Senescence in Osteoarthritis: Modulatory Actions of Olive Oil and Its Bioactive Compounds.

Osteoarthritis is a degenerative joint disorder characterized by progressive cartilage degradation, subchondral bone alterations, and persistent low-grade inflammation. Recent findings have identified a strong interplay between inflammation and cellular senescence in osteoarthritis. Chronic inflammatory signals promote the accumulation of senescent cells, while senescent cells amplify inflammatory pathways through their senescence-associated secretory phenotype (SASP). This bidirectional loop accelerates tissue damage by perpetuating oxidative stress, matrix degradation, and the release of proinflammatory mediators that reinforce the senescence process. Likewise, the biological activities of olive oil and its bioactive compounds, including monounsaturated and polyunsaturated fatty acids (PUFA), phenolic compounds (mainly ligstroside, oleocanthal, oleuropein, and hydroxytyrosol), squalene, phytosterols, vitamins (particularly vitamin E), and carotenoids, have attracted increased attention. These compounds may synergistically exert their effects through several interrelated mechanisms that influence both inflammatory and senescence pathways. They may modulate key signaling cascades, such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Toll-like receptors (TLRs), that drive the release of proinflammatory cytokines. Moreover, by attenuating SASP, olive oil compounds can potentially attenuate the vicious cycle between inflammation and senescence, slowing cartilage degradation and preserving joint function. Here, we synthesize current findings on the molecular mechanisms and clinical implications of bioactive compounds from olive oil, emphasizing their role in modulating both inflammation and senescence during osteoarthritis.