Abstract
Multiple lines of evidence suggest that high-dose vitamin D3 (cholecalciferol) can profoundly influence nuclear envelope integrity by modulating the expression and processing of lamin A—an essential nuclear scaffold protein that silences unneeded genes and maintains normal nuclear morphology. These effects are of particular interest in Hutchinson-Gilford progeria syndrome (HGPS), where a faulty lamin A (called progerin) drives accelerated aging, as well as in cancer cells that often downregulate lamin A to gain nuclear pliability. Recent in vitro work has shown that active vitamin D3 (1,25-dihydroxyvitamin D3 or calcitriol) reduces progerin production in HGPS cells while stabilizing critical DNA repair proteins such as BRCA1 and 53BP1, underscoring vitamin D’s broader role in genomic integrity. Furthermore, correcting lamin A deficits may force a shift from fermentative glycolysis (the Warburg effect) toward oxidative phosphorylation—supporting the metabolic theory that compromised mitochondrial function and a lax nuclear envelope go hand in hand in both cancer and progeria. This article also emphasizes the importance of supplementing vitamin K2 and magnesium when using high-dose vitamin D3 to avoid hypercalcemia.
