Anti-aging factor klotho linked to salt sensitive hypertension

Aging is associated with a number of health problems, of which hypertension or high blood pressure is one of the most common. Hypertension is called a silent killer because it causes no warning symptoms but it is one of the biggest preventable risk factors for death and disability around the world. High blood pressure is highly prevalent in elderly individuals and can be difficult to treat. There are no known clear markers that provide clues to a person’s risk of developing hypertension. A high-salt diet is a known risk factor for hypertension. In particular, elderly individuals tend to develop hypertension with high-salt intake. And while it has been observed that younger people are less salt sensitive (less likely to develop high blood pressure) than older people, the mechanism is not known. Now, scientists have discovered that the anti-aging protein Klotho, which is produced by the kidneys, has a protective effect. A report published in the Journal of Clinical Investigation reveals that increased salt sensitivity associated with aging may be mediated through Klotho. In the study, mice were found to have decreasing Klotho levels with age. The researchers identified a specific pathway called Wnt5a-RhoA through which Klotho prevents hypertension. “It took time to elucidate the molecular mechanism of salt-sensitive hypertension with aging. Although Klotho deficiency was known to activate Wnt signalling, the detailed mechanism by which Wnt activation causes vasoconstriction was unknown. We found that the Wnt signal has two pathways, the canonical pathway which was understood as significant in oncological research, but it took time to demonstrate that the Wnt-RhoA pathway of the non-canonical pathway causes vasoconstriction in cell experiments and mouse experiments,” says Professor Toshiro Fujita, corresponding author of the study. The researchers observed abnormal activation of this pathway could be reversed with Klotho supplementation in aged mice. This established Klotho deficiency as the cause of salt-sensitive hypertension. In the future, these breakthrough findings could lead to the development of a predictive hypertension marker which will help identify high-risk elderly individuals based on Klotho levels. Also, since Klotho decline is associated with the development of hypertension, supplementation with Klotho may help prevent high blood pressure in older adults. Human verification trials are underway. Scientists believe that a deficiency of Klotho protein may be related also to other age-associated conditions like sarcopenia and dementia. The mechanisms and pathways for this are currently being investigated