Klotho as a Biomarker of the Influence of Lifestyle Choice on Health – Fight Aging!

Klotho is a longevity-associated protein that operates both within the cell and also as a circulating signal protein. It is longevity-associated in the sense that upregulation increases life span and downregulation reduces life span in mice, but also in the sense that measured klotho levels correlate with health and life expectancy in human epidemiological studies. Klotho may largely operate by maintaining kidney function into late life, but researchers have found that it may also help brain cells resist the harmful effects of an aged environment.

In today’s open access paper, the authors make the interesting point that while epigenetic clocks are receiving attention as a potential way to assess the effects of lifestyle interventions on health and aging, there is in fact a great deal more existing evidence for the use of klotho as a biomarker in this context. Klotho may be a good enough reflection of the state of fitness, diet, and metabolic health to be used as a way to test compliance with lifestyle change in studies, or to assess the degree to which a given lifestyle change is in fact improving long-term health in any given individual.

The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements

With the global population aging, the number of people with multiple chronic health conditions has been rising because medicine still focuses on treatment rather than prevention. It is estimated that one in three people in the world lives with two or more chronic diseases. One way to prevent and even reverse chronic diseases is through lifestyle changes through health promotion and education. This also helps delay the onset of geriatric syndrome (frailty, cognitive decline, and reduced performance in the activities of daily living scale). This is why a new discipline of medicine has emerged to specifically address this issue: lifestyle medicine.

The American College of Lifestyle Medicine (ACLM) promotes a science-based approach that integrates lifestyle factors to prevent and treat chronic conditions. There are six pillars of lifestyle medicine: nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances. The goal of this discipline is not only to prolong the lifespan but to increase the healthspan by reducing the morbidity span. A study estimated that adherence to four or five low-risk lifestyle factors (diet, physical activity, alcohol intake, etc.) at age 50 could extend life expectancy free of major chronic diseases (cancer, cardiovascular disease, or diabetes) by 7.6 years in men and 10.6 years in women when compared to people with no low-risk lifestyle factors

Healthspan is defined as longevity without diseases and is often associated with a higher quality of life. Healthy longevity is a World Health Organization (WHO) priority. Chronological age, the number of years a person has been alive, is a great predictor of disease prevalence and mortality risk but is unchangeable. On the other hand, biological age is variable and measures the accumulation of physiological damage in individuals, meaning that two individuals of the same chronological age can have different biological ages. Thus, a biological marker providing a quantifiable overall insight into the patient’s current health status would be of great use.

A few longevity markers do currently exist, such as PhenoAge (algorithms to improve chronological age by adding 9 biomarkers found in routine blood tests) or GrimAge, which is an epigenetic clock that can evaluate the biological age of an individual using DNA methylation-based markers. These tests are reliable for determining biological age, but there is little literature linking them to healthspan potential and even less to each of the pillars of lifestyle medicine. A new biomarker, the longevity protein klotho, might become a game-changing tool for measuring metabolic health and predicting the potential for healthy longevity. This review introduces the klotho protein as a potential novel, cost-effective biomarker and integrative tool to quantify and monitor the health status of individuals adopting lifestyle behavioral changes and summarizes current knowledge on the extent of klotho regulation across the six pillars of lifestyle medicine.

Based on this narrative analysis, klotho is a very promising marker candidate for lifestyle medicine due to its potential involvement in the six pillars of lifestyle medicine. Although we have identified knowledge gaps that warrant further study (randomized trials) to better understand the use of klotho in monitoring the effect of a lifestyle change intervention, it has enormous potential to enable objective, quantitative, and rapid monitoring of the overall health and the healthspan of patients. Klotho could be used as a marker in clinical studies where it is difficult to control the entire patient environment. Klotho is easy to quantify and, in the case of age-related diseases, would be an excellent marker to follow, as some diseases show no perceptible symptoms for a long period of time.