High blood pressure and salt, anti-aging factor Klotho key

August 19, 2020

High blood pressure is often called a silent killer because it is the biggest risk factor for the most death and disability worldwide including heart disease and stroke, but presents no symptoms as a warning indicator. Many elderly people have high blood pressure that is difficult to treat, and good preventative methods and appropriate markers have not been elucidated.

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 is an anti-aging protein that 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 Wnt5a-RhoA pathway for the first time. The results showed that Klotho supplementation could prevent the development of hypertension, and Klotho levels could be a predictive marker for the development of hypertension.

Corresponding author and Specially Appointed Professor Toshiro Fujita of Shinshu University School of Medicine and Research Center for Social Systems, and Division of Epigenetics, Research Center for Advanced Science and Technology, University of Tokyo states that it took time, "to elucidate the molecular mechanism of salt-sensitive hypertension with aging. Although Klotho deficiency was known to activate Wnt signaling, 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."

In experiments using aged mice and cells, abnormal activation of the above 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.
For more information, please read the paper, Salt causes again-associated hypertension via vascular Wnt5a under Klotho deficiency in The Journal of Clinical Investigation.


This work was supported by Japan Society for the Promotion of Science KAKENHI (grants 18K08028, 15H05788, 15H02538, and 18K19533) and Japan Agency for Medical Research and Development-Advanced Research and Development Programs for Medical Innovation (AMED-CREST) (grant JP16gm0510009).

Shinshu University

Related Blood Pressure Articles from Brightsurf:

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

High blood pressure treatment linked to less risk for drop in blood pressure upon standing
Treatment to lower blood pressure did not increase and may decrease the risk of extreme drops in blood pressure upon standing from a sitting position.

Changes in blood pressure control over 2 decades among US adults with high blood pressure
National survey data were used to examine how blood pressure control changed overall among U.S. adults with high blood pressure between 1999-2000 and 2017-2018 and by age, race, insurance type and access to health care.

Transient increase in blood pressure promotes some blood vessel growth
Blood vessels are the body's transportation system, carrying oxygen and nutrients to cells and whisking away waste.

Effect of reducing blood pressure medications on blood pressure control in older adults
Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Here's something that will raise your blood pressure
The apelin receptor (APJ) has been presumed to play an important role in the contraction of blood vessels involved in blood pressure regulation.

New strategy for treating high blood pressure
The key to treating blood pressure might lie in people who are 'resistant' to developing high blood pressure even when they eat high salt diets, shows new research published today in Experimental Physiology.

Arm cuff blood pressure measurements may fall short for predicting heart disease risk in some people with resistant high blood pressure
A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Heating pads may lower blood pressure in people with high blood pressure when lying down
In people with supine hypertension due to autonomic failure, a condition that increases blood pressure when lying down, overnight heat therapy significantly decreased systolic blood pressure compared to a placebo.

Read More: Blood Pressure News and Blood Pressure Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.