Plasma klotho and mortality risk in older community-dwelling adults

Richard D. Semba, Anne R. Cappola, Kai Sun, Stefania Bandinelli, Mansi Dalal, Candace Crasto, Jack M. Guralnik, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)794-800
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume66 A
Issue number7
DOIs
StatePublished - Jul 2011

Keywords

  • Aging
  • Klotho
  • Longevity
  • Mortality

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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