It is imperative to understand calcium metabolism under a unified concept, despite the vast concentration difference among the three major calcium compartments in human body. Total body calcium homeostasis supported by adequate calcium intake and normal skeletal metabolism is quite important to maintain adequate extra- and intracellular calcium concentration gradient and consequent signal transduction system mediated by calcium entry into the cell. Aging and diseases are associated with blunting of the calcium concentration gradient, due to calcium deficiency and consequent secondary hyperparathyroidism.

The role of vitamin D in skin aging

The skin is the only tissue in the human body that represents both a target tissue for biologically active vitamin D compounds including 1,25-dihydroxy vitamin D [1,25(OH)2D] and has the capacity for the synthesis of 1,25(OH)2)D from 7-dehydrocholesterol (7-DHC). Recent findings indicate that the vitamin D endocrine system (VDES), besides multiple other important functions, regulates aging in many tissues, including skin. This concept is strongly supported by several independent studies in genetically modified mice (including FGF23-/- and Klotho-/- mice) that are characterized by altered mineral homeostasis caused by a high vitamin D activity.

These mice typically have phenotypic features of premature aging that include, besides short lifespan, retarded growth, ectopic calcification, immunological deficiency, osteoporosis, atherosclerosis, hypogonadism, skin and general organ atrophy. Notably, it has been demonstrated that these phenotypic features can be reversed by normalizing mineral homeostasis and/or vitamin D status. Interestingly, the aging phenotypes of mice suffering from hypovitaminosis D (VDR-/- and CYP27B1-/- mice) are quite similar to those suffering from hypervitaminosis D (including FGF-23-/- and Klotho-/- mice).

Consequently, it has been hypothesized that thus, both hypo- and hypervitaminosis D may enhance aging. Aging seems to show a U-shaped response curve to vitamin D status, and, therefore normo vitaminosis D seems to be important for preventing premature aging.

Additionally, laboratory investigations have now convincingly shown that vitamin D compounds protect the skin against the hazardous effects of various skin aging-inducing agents, including ultraviolet (UV) radiation. In conclusion, these findings support the concept that UV-radiation exerts both skin aging-promoting and inhibiting effects, the latter via induction of cutaneous vitamin D synthesis.

Future studies will clarify the effect of vitamin D compounds on expression and function of potential key regulators of skin aging, such as TAp63 or the IGF-1 signaling pathway. Furthermore, the efficacy of topically applied vitamin D compounds in the prevention of skin aging has to be evaluated in future clinical trials.

Vitamin D and anti-aging medicine

Vitamin D has many important roles in calcium and phosphorus metabolisms, the prevention of cancer, therapeutic effects of autoimmune disease, and the protective effects on atherosclerotic cardiovascular disease and diabetes. These functions are quite essential factors for the treatment of anti-aging medicine. We had given 1,000 IU/day vitamin D(3) to the patients who had low vitamin D levels in their blood and confirmed the increased vitamin D levels into the optimal range after the treatment. To keep the normal functions of the bone mineral metabolisms and the immune function, it is clinically relevant to detect the vitamin D levels in the blood and support these levels using supplements in the vitamin D deficient patients. Vitamin D is now one of the most essential vitamins in the anti-aging medicine.

(Article by Dr. Thiago Frere and Dipti Shitole).