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The predicted binding pose revealed that the compound establishes stabilizing interactions with a set of hydrophobic and aromatic residues lining the transmembrane binding cavity (Figure 4), including A200, L201, M204, L217, Y220, V229, and W297

Copper deficiency compromises cuproenzyme function, causing mitochondrial dysfunction (via impaired CCO), reduced antioxidant defense (via SOD downregulation), and structural defects (via reduced LOX activity leading to fibrosis)

Abbreviations 4EBP1: 4E-binding protein 1 AcCoA: Acetyl coenzyme A ACC: Acetyl-CoA carboxylase ATF3: Activating transcription factor 3 ATF4: Activating transcription factor 4 AP1: Activator protein-1 AGEs: Advanced glycation end products AOPP: Advanced oxidation protein products AFB1: Aflatoxin B1 AD: Alzheimer's disease ACLT: Anterior cruciate ligament transection ATM: Ataxia-telangiectasia mutated ACLY: ATP citrate lyase CaMKK: Ca2+/calmodulin-dependent protein kinase kinase CaMKKb: Ca2+/calmodulin-dependent protein kinase kinase beta CAMKK2: Calcium/calmodulin-dependent protein kinase kinase II CR: Calorie restriction CRMs: Calorie restriction mimetics CIT: Cap-independent translation CAT: Catalase CLS: Chronological lifespan DSS: Dextran sodium sulfate dTOR: Drosophila TOR homolog ETC: Electron transport chain eNOS: Endothelial nitric oxide synthase eEF2k: Eukaryotic elongation factor 2 kinase FeNCPs: Fe-5,5-azosalicylic acid nanoscale coordination polymer FKBP-12: FK506-binding protein GLP-1: Glucagon-like-peptide-1 GLUT 1-14: Glucose transporters GTPCH-1: GTP Cyclohydrolase 1 GAP: GTPase-activating protein Hsp90: Heat-shock protein 90 HFD: High-fat diet HMGB1: High-mobility group box 1 HAT: Histone acetyltransferase HOMA-IR: Homeostatic model assessment of insulin resistance HIF-1 : Hypoxia-inducible factor-1 HIF-1: Hypoxia-inducible factor-1 IGF-1: Insulin-like growth factor 1 ICAM-1: Intercellular adhesion molecule-1 IRS1 KO: IRS1 knockout LPL: Lipoprotein lipase LKB1: Liver kinase B1 mTOR: Mammalian target of rapamycin mTORC1: Mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1 MAP1S: Microtubule-associated protein 1S TFAM: Mitochondrial transcription factor A MCP-1: Monocyte chemotactic protein 1 NOX: NADPH oxidase NAD + : Nicotinamide adenine dinucleotide NMN: Nicotinamide mononucleotide NAMPT: Nicotinamide phosphoribosyltransferase NO: Nitric oxide NLRP3: NLR family pyrin-domain-containing-3 NSCLC: Non-small cell lung cancer NRF: Nuclear factor erythroid 2-related factor OCT: Organic cation transporter OS: Oxidative stress OCR: Oxygen consumption rate PPAR-: Peroxisome proliferated activated receptor PPARGC1A: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC1: Peroxisome proliferatoractivated receptor-gamma coactivator 1 PFK-2: Phosphofructokinase-2 PGI: Phosphoglucose isomerase PRPP: Phosphoribosyl pyrophosphate PDGF: Platelet-derived growth factor PACOS: Pre-acetylated chitosan rapalogs: Rapamycin and its analogs ROS: Reactive oxygen species RAGEs: Receptors of AGEs SaIONPs: Salicylic acid-functionalized iron oxide nanoparticles SASP: Senescence-associated secretory phenotype STAT: Signal transducer and activator of transcription SIRT1: Sirtuin 1 SKN-1: Skinhead-1 SGLT 1-2: Sodium-glucose cotransporters SPM: Spermine TGF-: Transforming growth factor beta TSC1: Tuberous sclerosis protein complex 1 T2DM: Type 2 diabetes mellitus ULK1: Unc-51 like autophagy activating kinase EZH2: Zeste homolog 2 References Abbas S, Wink M (2009) Epigallocatechin gallate from green tea ( Camellia sinensis ) increases lifespan and stress resistance in Caenorhabditis elegans

From a translational perspective, this raises the possibility that combined modulation of these pathways could stabilize the neurovascular unit and preserve cerebral homeostasis

Alvarez-Bagnarol Y, Marchette RC, Francis C, Morales M, Vendruscolo LF