Klotho is a gene associated with longevity and plays a key role within the cell. A portion of the full protein is also released into the bloodstream. In humans, higher levels of circulating klotho are linked to lower incidence of age-related diseases and mortality. In mice, interventions that increase klotho levels are shown to extend life, while reducing klotho levels shortens life. Klotho is believed to act within the kidney, protecting it against age-related decline in function. Increased klotho levels have been found to improve cognitive function in mice and non-human primates, and higher levels in humans are associated with lesser degrees of cognitive decline in later life. Some are exploring the delivery of klotho as a potential basis for therapies.
Recent research shows that while klotho levels and physical capabilities both decline with age, the degree of physical fitness at a given age does not appear to correlate with klotho levels. Therefore, increasing physical fitness in later life would not be expected to raise klotho levels. This is interesting because circulating klotho has been shown to correlate with parameters that should theoretically be improved by greater fitness, such as lower chronic inflammation in individuals with higher levels of circulating klotho.
A study has found that Klotho protein plays a crucial role in the development of functional impairments with aging. Klotho is a large transmembrane glycoprotein that is predominantly expressed in the distal convoluted tubules of the kidneys. Research demonstrated that Klotho-deficient mice exhibited a premature aging phenotype, including severe muscle wasting, hypokinesis, an abnormal walking pattern, and decreased stride length. This suggests a role for Klotho in regulating skeletal muscle function, muscle regeneration, mitochondrial biogenesis, oxidative stress, and inflammation. Additionally, other studies have shown that lower levels of Klotho are associated with increased disability in activities of daily living and higher risk of frailty, suggesting a strong connection between Klotho levels and physical function.
Another study sought to examine the relationship between serum Klotho levels and physical function in healthy adults across various age categories. The results showed that Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity. These findings suggest a strong association between lower Klotho levels and impaired physical function.
