Abstract
Background & Objective: The heart function declines in the aged population. At age 80 years, LV contractile function is less than half of what it was at age 20 years. Aging is a recognized risk factor for heart diseases. For instance, the prevalence of heart disease increases with age. The mortality from heart diseases is higher in the aged than in the young population. Klotho is a recently discovered anti-aging gene that is primarily expressed in kidneys. The secreted Klotho is released into blood. The objective of this study is to investigate if a decline serum Klotho levels contributes to aging-related heart failure. Method & Results: The results showed that ejection fraction, stroke volume and cardiac output were decreased in aged mice (24 months) vs. the adult mice (10 months), indicating that aging impairs heart function. The serum level of Klotho was decreased significantly in aged mice. Interestingly, daily injection of recombinant Klotho protein rescued the aging-related decline in heart function. Mutation of Klotho gene ( KL -/- ) resulted in heart failure which was associated with a significant increase in serum phosphate levels (hyperphosphatemia). Low phosphate diet delayed but did not prevent the development of heart failure in male KL -/- mice, suggesting that hyperphosphatemia partially contributes to Klotho deficiency-induced heart failure. Unfortunately, low phosphate diet failed to improve heart failure in female KL -/- mice. Interestingly, administration of estrogen decreased hyperphosphatemia and delayed the development of heart failure in KL -/- although it did not prevent Klotho deficiency-induced heart failure. Therefore, Conclusion: Klotho deficiency contributes to aging-related heart failure. Hyperphosphatemia accelerated the development of Klotho deficiency-induced heart failure. Administration of recombinant Klotho protein is an effective therapeutic strategy for heart aging. (supported by NIH R01 HL118558, AG049780, DK093403).
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call