title: Plasma klotho and mortality risk in older community-dwelling adults.
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.
authors.affiliation: Baltimore, MD 21287, USA. rdsemba@jhmi.edu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Mansi
authors.initials: M
authors.lastname: Dalal
authors.forename: Candace
authors.initials: C
authors.lastname: Crasto
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death / Q000639:trends; D016001:Confidence Intervals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D015577:Geriatric Assessment / Q000379:methods*; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D000090265:Klotho Proteins; D008136:Longevity / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000090265:Klotho Proteins