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Senescence was first described by Leonard Hayflick upon the observation that human fetal fibroblasts eventually stopped dividing but remained viable and metabolically active after prolonged time in culture

Biochim Biophys Acta 1824:157163 Herrera MG, Pizzuto M, Lonez C, Rott K, Htten A, Sewald N, Ruysschaert JM, Dodero VI (2018) Large supramolecular structures of 33-mer gliadin peptide activate toll-like receptors in macrophages

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Collectively, these clinical experiences highlight a key translational challenge: even when therapeutic targets are biologically validated, inefficient CNS delivery limits treatment efficacy while increasing systemic burden