Plasma klotho and frailty in older adults: Findings from the InCHIANTI Study.

Background: The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations have been linked to better physical performance; however, it is unknown whether klotho relates to frailty status in older adults.

Methods: Plasma klotho was measured in 774 participants aged ≥ 65 years enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Frailty status was assessed at three and six years after enrollment. Frailty was defined as presence of at least three out of the five criteria of unintentional weight loss, exhaustion, sedentariness, muscle weakness, and slow walking speed; prefrailty was defined as presence of one or two criteria; and robustness was defined as zero criteria. We assessed whether plasma klotho concentrations measured at the three-year visit related to frailty.

Results: Each additional natural logarithm of klotho (pg/mL) was associated with lower odds of frailty versus robustness after adjustment for covariates (Odds Ratio [OR] 0.46; 95% confidence interval [CI] 0.21, 0.98; p-value=0.045). Higher klotho was particularly associated with lower odds of exhaustion (OR 0.57; 95% CI 0.36, 0.89; p-value=0.014). Participants with higher klotho also had lower estimated odds of weight loss and weakness, but these findings were not statistically significant.

Conclusions: Higher plasma klotho concentrations were associated with lower likelihoods of frailty and particularly exhaustion. Future studies should investigate modifiable mechanisms through which klotho may affect the frailty syndrome.