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This decline leads to insufficient activation of sirtuins (SIRT1SIRT7)NAD+-dependent deacetylases that regulate mitochondrial biogenesis via PGC-1, DNA repair, and cellular stress resistance

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Moreover, experimental evidence demonstrates that calcitriol enhances the expression of multiple tight junction proteinsincluding claudin-4/7, occludin, and ZO-1via activation of PI3K/Akt and atypical PKC (aPKC) signaling pathways, thereby significantly increasing transepithelial electrical resistance (TER) and reinforcing barrier homeostasis [109]

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