Oleuropein Aglycone Modulates Oxidative Stress and Autophagy-Related Pathways in Human Skeletal Muscle Cells

Abstract

A gradual loss of muscle mass and strength increases the risk of falls, frailty and mortality. It is the result of a combination of intrinsic factors such as oxidative stress, mitochondrial dysfunction and extrinsic factors such as poor nutrition and inactivity. Oleuropein aglycone (OLE), a compound extracted from olive leaves, combats oxidative damage through its antioxidant and autophagy-inducing properties. It activates AMPK and FOXO3a signaling pathways, autophagy, mitochondrial function and muscle health. OLE is investigated in the human immortalized myoblast cell line AB1079 for its protective effect against muscle oxidative stress. Oxidative stress was induced in the AB1079 cell line after 7 days of differentiation by hydrogen peroxide (H₂O₂), leading to a significant increase in reactive oxygen species formation, which was reduced by approximately 43% by pretreatment with OLE. Cells treated with H₂O₂ showed a 33% increase in stress-induced senescent cells, while pretreatment with OLE significantly reduced the stained area of the X-gal reaction by 12% compared to H₂O₂. OLE increased the expression of genes involved in antioxidant defense and influencing the autophagic process by inducing an oscillator AMPK phosphorylation, as well as the expression of the stress-induced metabolic regulators SESN2 and SESN3. OLE has been shown to counteract the oxidative environment and promote autophagy-related signaling in vitro, suggesting a potential role in preventing cellular mechanisms associated with muscle aging. Further in vivo studies are required to confirm functional anti-aging effects.

Keywords: ROS; aging; human skeletal muscle cells; oleuropein aglycone.