Plasma Klotho and Frailty in Older Adults: Findings From the InCHIANTI Study

J Gerontol A Biol Sci Med Sci. 2019 Jun 18;74(7):1052-1057. doi: 10.1093/gerona/glx202.


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 3 and 6 years after enrollment. Frailty was defined as presence of at least three out of 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 3-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 0.21, 0.98; p-value = .045). Higher klotho was particularly associated with lower odds of exhaustion (OR 0.57; 95% CI 0.36, 0.89; p-value = .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.

Keywords: Biomarkers; Endocrinology; Epidemiology; Frailty syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • Correlation of Data
  • Female
  • Frail Elderly / psychology
  • Frailty* / blood
  • Frailty* / diagnosis
  • Frailty* / physiopathology
  • Glucuronidase / blood*
  • Healthy Aging* / physiology
  • Healthy Aging* / psychology
  • Humans
  • Italy
  • Klotho Proteins
  • Male
  • Muscle Weakness* / diagnosis
  • Muscle Weakness* / etiology
  • Physical Functional Performance
  • Sedentary Behavior
  • Walking Speed
  • Weight Loss


  • Biomarkers
  • Glucuronidase
  • Klotho Proteins