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Abbreviations HTY: Hydroxytyrosol (3, 4-dihydroxyphenylethanol) EVOO: Extra virgin olive oil Nrf2: Nuclear factor erythroid 2-related factor 2 NF-B: Nuclear factor kappa-light-chain-enhancer of activated B cells AMPK: AMP-activated protein kinase Keap1: Kelch-like ECH-associated protein 1 ROS: Reactive oxygen species HAT: Hydrogen atom transfer GPX4: Glutathione peroxidase 4 ACSL4: Acyl-CoA synthetase long-chain family member 4 GRAS: Generally recognized as safe EFSA: European food safety authority NOAEL: No-observed-adverse-effect level EC50 / IC50: Half-maximal effective/inhibitory concentration Kd: Dissociation constant ORAC: Oxygen radical absorbance capacity FRAP: Ferric reducing antioxidant power MDA: Malondialdehyde SOD: Superoxide dismutase CAT: Catalase NQO1: NAD(P)H quinone oxidoreductase 1 HO-1: Heme oxygenase 1 LDL: Low-density lipoprotein HDL: High-density lipoprotein TNF-: Tumor necrosis factor alpha IL-1: Interleukin 1 beta eNOS: Endothelial nitric oxide synthase PI3K/Akt/mTOR: Phosphoinositide 3-kinase / protein kinase B MAPK: Mitogen-activated protein kinase HIF1: Hypoxia-inducible factor 1 alpha GPER: G protein-coupled estrogen receptor ERK1/2: Extracellular signal-regulated kinase 1/2 Tmax: Time to maximum plasma concentration Cmax: Maximum plasma concentration HVA: Homovanillic acid DOPAC 3,4: Dihydroxyphenylacetic acid RCT: Randomized controlled trial References Casaburi I, et al

Since immune cell trafficking into the CNS is tightly regulated by the blood brain barrier which selectively only allows entry of immune cell subsets required for immune surveillance (80), it remains unknown if CAR-T would efficiently reach senescent cells in the brain parenchyma