Vitamin D Nutrient-Gene Interactions and Healthful Aging

1,25-Dihydroxyvitamin D₃ (1,25D) is the endocrine metabolite of vitamin D that signals through binding to the vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes that encode factors promoting intestinal calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling further exerts feedback control of mineral ions via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, and associated pathologies. Vitamin D also elicits xenobiotic detoxification, oxidative stress reduction, antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions, and cardiovascular benefits. 1,25D exerts neuroprotective actions against excitotoxicity, and induces serotonin mood elevator to support cognitive function and prosocial behavior. Nutrient, low-affinity VDR ligands including curcumin, polyunsaturated fatty acids, and delphinidin/anthocyanidins initiate VDR signaling, whereas longevity agents such as resveratrol and SIRT1 potentiate VDR signaling. Therefore, liganded VDR modulates the expression of a network of genes that facilitates health span by delaying the chronic diseases of aging.