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April 13, 2011

Anti-aging hormone Klotho may prevent complications in chronic kidney disease

Low levels of the anti-aging hormone Klotho may serve as an early warning sign of the presence of kidney disease and its deadly cardiovascular complications, according to findings by UT Southwestern Medical Center researchers.

Using mice, investigators found that soft-tissue calcification, a common and serious side effect of chronic kidney disease (CKD), improves when Klotho hormone levels are restored. The study is available online in the Journal of the American Society of Nephrology.

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You might recall the identification of klotho as a longevity-related gene in mice and other lower animals in recent years. Here is a study on levels of klotho in humans: "The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans. ... We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. ... During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho [had] an increased risk of death compared with participants in the highest tertile of plasma klotho ... In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans." Given the number of adjustments there, I'd like to see a confirming study - and for preference one that explicitly took into account calorie intake as well. Just because you see the expected result is no reason to abandon the usual level of caution needed when reading the output of the scientific method.

Journal of Gerontology and Biological Science Medical Science - Plasma Klotho and Mortality Risk in Older Community-Dwelling Adults

In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.
According to the research, Klotho lessens vascular calcification by enhancing the urine’s phosphate excretions (essential for building and repairing bones and teeth, helping nerve function and making muscles contract, but it can be toxic when levels are high); and preserving kidney fluid filtration. Most importantly, Klotho also appears to inhibit vascular smooth-muscle phosphate uptake and calcification, a complication of CKD that can significantly increase risk of death.

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