Plasma klotho and mortality risk in older community-dwelling adults

J Gerontol A Biol Sci Med Sci. 2011 Jul;66(7):794-800. doi: 10.1093/gerona/glr058. Epub 2011 Apr 7.

Abstract

Background: The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans.

Methods: We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy.

Results: During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho (<575 pg/mL) had an increased risk of death compared with participants in the highest tertile of plasma klotho (>763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20-2.63).

Conclusions: In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aging / blood*
  • Biomarkers / blood
  • Cause of Death / trends
  • Confidence Intervals
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Geriatric Assessment / methods*
  • Glucuronidase / blood*
  • Humans
  • Italy / epidemiology
  • Longevity / physiology*
  • Male
  • Motor Activity / physiology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • Time Factors

Substances

  • Biomarkers
  • Glucuronidase
  • klotho protein