Relationship between klotho and physical function in healthy aging

“Longevity Protein”—— Klotho levels decline as early as 50 years old, potentially before the onset of age-related impairment in exercise capacity.

Epidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.

Open Access Paper:

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Another reason to take a SLG-2 inhibitor, for example Canagliflozin

Sodium-glucose co-transporter-2 inhibitors increase Klotho in patients with diabetic kidney disease: A clinical and experimental study


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

Aging is not a disease; it is a natural evolution of human physiology. Medical advances have extended our life expectancy, but chronic diseases and geriatric syndrome continue to affect the increasingly aging population. Yet modern medicine perpetuates an approach based on treatment rather than prevention and education. In order to help solve this ever-growing problem, a new discipline has emerged: lifestyle medicine. Nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances are the pillars on which lifestyle medicine is founded. The aim of this discipline is to increase healthspan and reduce the duration of morbidity by making changes to our lifestyle. In this review, we propose the use of klotho protein as a novel biomarker for lifestyle medicine in order to quantify and monitor the health status of individuals, as no integrative tool currently exists.


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.

The world’s population is growing, aging, and becoming increasingly sedentary. A healthcare system that focuses solely on treatment is unsustainable, and if this trend continues, healthcare costs will be astronomical as the population’s health declines. The recent pandemic has shown us the capabilities of modern science and the importance of being healthy. It has also clearly demonstrated the extent of social inequalities on a global scale. A 2019 report by The Institute of Health Metrics and Evaluation analyzed data from more than 190 countries and found that what people eat and fail to eat is the leading cause of disease and death [37]. Health promotion and prevention, coupled with simple, cost-effective biomarkers, will become a necessity for tomorrow’s medicine. Lifestyle medicine and allopathic medicine are not mutually exclusive but rather work together in the patient’s best interest. We must invest in health today to reap the benefits later, but first, efforts need to be focused where they are needed most so that health becomes accessible to all. Health is a multifactorial concept, and as long as there are low-income areas, low levels of education, and food-insecure households, inequalities will persist, as will chronic disease.

Open access paper: Metabolites | Free Full-Text | The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements


I found this new (at least for my limited knowledge):

A low-calorie, high-protein diet increases klotho levels in a rat’s brain, while a phosphate-restricted diet improves klotho kidney expression in a mouse model of polycystic kidney disease [45].

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Anyone know how to measure/test it?