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This compensatory mechanism is highly sensitive to changes in renal function, as even partial unilateral infarction, induced by ligation of one-half of the renal arteries, can be sufficient to increase IGF-1 expression in the contralateral kidney.19 Mechanistically, the upregulation of renal IGF-1 expression is stimulated by epidermal growth factor (EGF) in the renal collecting ducts, indicating a paracrine regulatory mechanism, as both, IGF-1 and EGF, are produced locally within the kidney.20 Moreover, the renal anabolic effects of IGF-1 are partly mediated through activation of the AKT-calcineurin-NFATc1 signaling pathway, which is involved in the regulation of vascular endothelial growth factor (VEGF).21,22 More recently, studies using single-cell RNA sequencing, have revelated that renal hypertrophy in mice activates sterol regulatory element-binding protein 2 (SREBP2) and increases cholesterol biosynthesis in medullary thick ascending limb cells

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Alterations in other melanogenesis-related genes, such as tyrosinase-related proteins (TRPs) and melanocyte-inducing transcription factor (MITF), further contribute to graying

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