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Proposed mechanisms include upregulation of growth-hormone-receptor expression in injured tissue, VEGF-driven angiogenesis, modulation of the nitric-oxide pathway in vascular endothelium, and activation of FAK-paxillin signaling

The Sacklers were

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Unlike peptides that require brain penetration, klotho enhances cognition when administered peripherallydespite not crossing the blood-brain barriersuggesting it acts through systemic signaling mechanisms that remain incompletely understood