Vitamin D, calcium homeostasis and you may aging
Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2Dstep three action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed https://datingranking.net/mumbai-dating/. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance.
Calcium is the 5th really numerous element in the human body and is essential for lifetime. 1 It has a switch role in lot of emotional processes together with skeletal mineralization, strength contraction, nerve response transmission, blood clotting, and you can hormone hormonal. More 99% of calcium in the human body are kept in the fresh new bones just like the hydroxyapatite, that provides skeletal power which can be a supply of calcium to own the several calcium supplements-mediated functions as well as for the repairs out-of serum calcium within the typical range (8–ten milligrams·dL ?step 1 ). Below step 1% off calcium supplements is located in the newest blood, softer structures, and you may extracellular fluid. Serum calcium is actually both protein-sure (
51%). 1 It is the ionized calcium that is available to enter cells and result in the activation of essential physiological processes. Calcium is only available to the body through dietary intake. In the elderly there is inadequate intestinal absorption of calcium combined with an age-related hormonal decline, which results in adverse effects on bone health. 2,3 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D, is the major controlling hormone of intestinal calcium absorption. 4 Calcium homeostasis is also regulated by parathyroid hormone and ionized calcium. 1,5 This review will focus on mechanisms involved in vitamin D regulation of calcium homeostasis, changes that occur with aging and current recommendations to address deficiencies.
Vitamin D is derived from the diet from fortified dairy products and fish oils or is synthesized in the skin from 7-dehydrocholesterol by ultraviolet irradiation. 6,7 Vitamin D is transported in the blood by vitamin D-binding protein (DBP). A series of hydroxylations, the first one at the 25th carbon (C-25) and the second at carbon 1 (C-1), are needed to produce the active form of vitamin D, 1,25(OH)2D3. 25-Hydroxylation of vitamin D in the liver results in the formation of 25-hydroxyvitamin D [25(OH)D3], the major circulating form of vitamin D and the most reliable index of vitamin D status. 6,7 CYP2R1 is now considered the key enzyme responsible for the conversion of vitamin D to 25(OH)Dstep 3. 8,9 Studies in CYP2R1 null mice, indicating significantly reduced levels of 25(OH)D3 in these mice, have confirmed the role of CYP2R1 in the hydroxylation of vitamin D at C-25. 10 However, synthesis of low levels of 25(OH)D3 in these mice suggests that other 25-hydroxylases, yet to be identified, are also involved in the conversion of vitamin D to 25(OH)D3. After its synthesis in the liver, 25(OH)D3 is transported by DBP to the kidney where it is internalized by megalin, a transmembrane protein that acts as a surface receptor for DBP. 11,12 In the proximal renal tubule, 25(OH)D3 is hydroxylated by 25(OH)D3 1? hydroxylase (CYP27B1) resulting in the formation of 1,25(OH)2D3, which is responsible for the biological actions of vitamin D. In humans, mutations resulting in nonfunctional or deleted CYP27B1 cause vitamin D dependency rickets type 1 (characterized by hypocalcemia, hyperparathyroidism, and decreased bone mineralization), indicating the importance of CYP27B1 for the maintenance of calcium homeostasis. 13 25-Hydroxyvitamin D3 24hydroxylase (CYP24A1) is the enzyme responsible for the catabolism of 1,25(OH)2D. 14,15 Direct evidence for a role of CYP24A1 in 1,25(OH)2D3 catabolism was provided by studies in CYP24A1 null mice. The survival rate of homozygous mutants is