Abstract: BACKGROUND: Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.
OBJECTIVE: To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice, and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism, so as to provide a reference for the influence of long-term endurance exercise on natural aging.
METHODS: Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups: young and quiet control group, natural aging quiet group and natural aging exercise group. Mice in the young and quiet control group were then killed immediately. Mice in the natural aging quiet group were raised normally until 60 weeks of age. Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week, followed by the maximum running speed test. The official exercise speed was set at 70% of the maximum running speed, and exercise was performed on Mondays, Wednesdays, and Fridays for 50 minutes each. Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks. (3) Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23, renal fibroblast growth factor receptor 1, 1α-hydroxylase, and serum 1,25(OH)2D3.
RESULTS AND CONCLUSION: (1) Compared with the young and quiet control group, serum calcium and phosphorus levels in natural aging quiet group had no significant changes (P > 0.05), but bone calcium and phosphorus levels were significantly reduced (P < 0.01). Compared with the natural aging quiet group, the serum phosphorus level was significantly reduced (P < 0.05), the serum calcium level did not change (P > 0.05), and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group (P < 0.05). (2) Compared with the young and quiet control group, the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased (P < 0.05). Compared with the natural aging quiet group, the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced, but it was not statistically significant (P > 0.05). (3) Compared with the young and quiet control group, the renal Klotho protein expression, the renal fibroblast growth factor receptor 1, 1α-hydroxylase, and serum 1, 25(OH)2 D3 levels in the natural aging quiet group were significantly decreased (P < 0.05, P < 0.01). Compared with the natural aging quiet group, the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group (P < 0.05, P < 0.01). To conclude, long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis, thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)₂D₃, and further regulating the body's calcium and phosphorus metabolism, especially phosphate metabolism. This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.

Key words: natural aging mice, kidney Klotho, fibroblast growth factor 23, kl/FGF23 axis, calcium-phosphorus metabolism