Posted on Aug 21, 2020, 2 p.m.
A report published in the Journal of Clinical Investigation has found for the first time a deficiency in Klothos, which is an anti-ageing factor produced in the kidneys, causing ageing associated hypertension through high salt intake. Ageing has been associated with a high prevalence of hypertension due to the increased susceptibility of blood pressure to dietary salt, but the mechanism is unknown.
High blood pressure is known as a silent killer as it is one of the biggest risk factors for the most death and disability on a global scale, but it presents no symptoms as a warning indicator. Many people, especially the elderly, have high blood pressure levels that can be hard to treat, and appropriate markers are not fully clear.
The anti-ageing protein Klotho acts as a hormone, and it is secreted into the blood from the kidneys, but its presence decreases with age leading to the vascular and arterial system to stiffen. This recent study shows the relationship between Klotho concentration and blood pressure salt sensitivity. While hypertension can be caused by excessive salt intake the sensitivity of blood pressure to salt can vary from person to person, and those who are highly sensitive are more likely to have high blood pressure.
Typically younger people are less sensitive, as such they are less likely to develop hypertension while older people are more sensitive and more likely to develop hypertension. The mechanism through which increased salt sensitivity occurs with ageing is unknown.
In this study, salt-sensitive was confirmed to increase in aged mice and revealed that the cause was that the blood concentration of Klotho protein decreasing with age. To add to this the researchers clarified the molecular mechanism Wnt5a-RhoA pathway for the first time. Findings indicate that Klotho supplementation may prevent the development of hypertension, and levels of Klotho may be a predictive marker for the development of hypertension.
Professor Toshiro Fujita, who is the corresponding author, wrote that 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."
Abnormal activation of this pathway was observed to be reversed with supplementation of Klotho proteins during experiments with aged mice and cells, as such it was possible to establish that the cause of salt-sensitive hypertension due to ageing is Klotho decline.
Breakthrough findings suggest that Klotho supplementation may help to prevent the development of hypertension in the elderly, and levels could be a predictive marker for the development of hypertension. Trails for human verification are underway.
Ageing is a universal phenomenon that can cause hypertension, dementia, frailty, and can also impair the healthy life expectancy of people. Klotho protein deficiency may be related to the onset of dementia and sarcopenia that is associated with ageing, these onset mechanisms are still currently under investigation.
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