Involvement of oxysterols in age-related diseases and ageing processes

• Oxysterols are oxidized derivatives of cholesterol.
• Oxysterols arise from cholesterol by autoxidation or by specific enzymes.
• Oxysterols are involved in several non tumoral and tumoral age-related diseases.
• Oxysterol-induced cell death, oxidation and inflammation could contribute in ageing.

Ageing is accompanied by increasing vulnerability to major pathologies (atherosclerosis, Alzheimer's disease, age-related macular degeneration, cataract, and osteoporosis) which can have similar underlying pathoetiologies. All of these diseases involve oxidative stress, inflammation and/or cell death processes, which are triggered by cholesterol oxide derivatives, also named oxysterols. These oxidized lipids result either from spontaneous and/or enzymatic oxidation of cholesterol on the steroid nucleus or on the side chain. The ability of oxysterols to induce severe dysfunctions in organelles (especially mitochondria) plays key roles in RedOx homeostasis, inflammatory status, lipid metabolism, and in the control of cell death induction, which may at least in part contribute to explain the potential participation of these molecules in ageing processes and in age related diseases. As no efficient treatments are currently available for most of these diseases, which are predicted to become more prevalent due to the increasing life expectancy and average age, a better knowledge of the biological activities of the different oxysterols is of interest, and constitutes an important step toward identification of pharmacological targets for the development of new therapeutic strategies.

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