Klotho is a longevity-associated protein. More of it in mice extends life, less of it shortens life. In humans, a number of studies have shown klotho levels to correlate with longevity. Beyond life span, a higher level of klotho also positively influences cognitive function, but the evidence to date shows the protein acting in the kidney. Researchers here demonstrate a link to hypertension, which is quite interesting, as the raised blood pressure of hypertension is strongly linked to both age-related mortality and cognitive decline. Increased blood pressure accelerates the progression of vascular conditions such as hypertension, leads to heart failure, and causes pressure damage to delicate tissues such as the brain. Sustained control of blood pressure is well demonstrated to reduce mortality in older people.

It has been known that high salt intake causes hypertension, but its exact mechanism was not understood until this study which found for the first time that Klotho deficiency, an anti-aging factor produced in the kidneys, causes aging-associated hypertension through high salt intake. Klotho acts as a hormone and is secreted into the blood from the kidneys. Its presence decreases with age causing the vascular and arterial system to stiffen. A recent study had shown the inverse relationship between the Klotho concentration and BP salt sensitivity. Hypertension is caused by excessive intake of salt, but the sensitivity of blood pressure to salt varies from individual to individual, and highly sensitive people are more likely to have high blood pressure.

In general, young people are less sensitive and are unlikely to develop hypertension, whereas older people are more sensitive to salt and are likely to develop hypertension. However, the mechanism of increased salt sensitivity with aging was unknown. Therefore, the research group first confirmed that salt sensitivity increased in aged mice, and revealed that the cause is that the blood concentration of the anti-aging factor Klotho protein decreases with age. Furthermore, the group clarified the molecular mechanism Wnt5aRhoA pathway for the first time. In experiments using aged mice and cells, abnormal activation of this pathway could be reversed by supplementation with Klotho protein. As a result, it was possible to establish that the cause of salt-sensitive hypertension due to aging is Klotho protein decline.

The results of this experiment showed that Klotho supplementation could prevent the development of hypertension in the elderly and that Klotho levels could be a predictive marker for the development of hypertension. Trials for human verification is currently underway. Aging, a universal phenomenon, causes not only hypertension but dementia and frailty, and impairs the healthy life expectancy of individuals. The aging-related phenomenon of Klotho protein deficiency may be related to the onset of dementia and sarcopenia, or the loss of muscle-mass and usage associated with aging. Its onset mechanism is currently under investigation.

Link: https://www.eurekalert.org/pub_releases/2020-08/su-hbp081920.php