不老長寿のためには過剰なリン負荷の抑制が重要である
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概要
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Serum phosphorus (P) is tightly maintained within the physiological range by regulation of dietary absorption and renal excretion in healthy individuals, because P plays a fundamental physiological role in energy metabolism, nucleic acid synthesis, and cellular signal transduction. Hyperphos-phatemia is one of common complications of chronic kidney disease (CKD). Observational studies have identified hyperphosphatemia as an independent non-traditional risk factor for cardiovascular disease (CVD) and mortality in CKD. The reason is considered because hyperphosphatemia is also a major risk factor for vascular calcification (VC). It was reported that higher serum P concentration, albeit within the normal range, was associated with development of atherosclerosis and increased mortality in the general population, suggesting that excessive P loading, even if it does not cause hyperphosphatemia, can be a risk factor for CVD regardless of renal function. Aging is one of the potent risk factors for any age-related diseases, including cancer, CVD, and stroke. Suppression of aging would be the effective way to reduce mortality and improve quality of life. In murine models, deletion of the fibroblast growth factor-23 or Klotho gene is associated with a phenotype characterized by hyperphosphatemia, premature aging, and VC, which is reversed by lowering serum P level. These results suggest that the suppression of excessive P loading is important for prevention of premature aging, including VC. Therefore, I review the physiological role and regulation of P, and highlight recent findings of phosphate toxicity for the cell, including the potential link between aging and P, in this article.
- 2013-05-24