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Accelerated suicidal erythrocyte death in Klotho-deficient mice
Daniela S Kempe1, Teresa F Ackermann, Stephanie S Fischer
1Department of Physiology, University of Tübingen, Tübingen, Germany.
Pflugers Archiv : European Journal of Physiology
|February 3, 2009
Summary
Klotho protein deficiency accelerates aging and shortens lifespan by increasing calcium influx into red blood cells, promoting suicidal erythrocyte death (eryptosis). This effect is partially mediated by vitamin D and can be reversed by a vitamin D-deficient diet.
Area of Science:
- Gerontology
- Cell Biology
- Endocrinology
Background:
- Klotho is a protein that counteracts aging and extends lifespan, with Klotho deficiency leading to a significantly shorter life span in mice.
- Klotho inhibits the formation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a metabolite that stimulates calcium entry into cells.
- Increased intracellular calcium in erythrocytes can trigger eryptosis, a form of suicidal cell death characterized by shrinkage and phosphatidylserine exposure.
Purpose of the Study:
- To investigate the impact of Klotho on eryptosis.
- To determine if Klotho deficiency affects erythrocyte calcium levels and suicidal death.
- To explore the role of vitamin D in the relationship between Klotho and eryptosis.
Main Methods:
- Comparison of erythrocyte cytosolic Ca(2+) concentration, phosphatidylserine exposure, and cell volume between Klotho-deficient (klotho(-/-)) and wild-type (klotho(+/+)) mice.
- Assessment of eryptosis markers under conditions of energy depletion and oxidative stress.
- Evaluation of the effects of a vitamin D-deficient diet on erythrocyte parameters in klotho(-/-) mice.
- Measurement of reticulocyte number to assess erythrocyte turnover.
Main Results:
- Klotho-deficient erythrocytes exhibited significantly higher cytosolic Ca(2+) concentration, enhanced phosphatidylserine exposure, and decreased cell volume compared to wild-type erythrocytes.
- Energy depletion and oxidative stress exacerbated phosphatidylserine exposure in klotho(-/-) erythrocytes.
- Reticulocyte number was significantly increased in klotho(-/-) mice, indicating enhanced erythrocyte turnover.
- A vitamin D-deficient diet reversed the increased Ca(2+) entry and phosphatidylserine exposure in klotho(-/-) erythrocytes.
Conclusions:
- Klotho deficiency leads to increased eryptosis, at least partially through vitamin D-dependent regulation of erythrocyte calcium levels.
- Klotho plays a novel role in regulating erythrocyte calcium homeostasis and preventing suicidal erythrocyte death.
- These findings link Klotho, vitamin D, and eryptosis, offering new insights into aging and red blood cell survival.
