The frequency of Klotho KL-VS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect

Biogerontology. 2010 Feb;11(1):67-73. doi: 10.1007/s10522-009-9229-z. Epub 2009 May 7.


In mice a defect of Klotho gene expression results in multiple aging-like phenotypes including short lifespan, osteoporosis and atherosclerosis, while its over-expression suppresses aging and extends lifespan. Contrasting data have been reported as far as the importance of the functional variant of Klotho termed "KL-VS" on human longevity, depending on the average age of the old subjects that were compared with young controls. We therefore performed a study on a large Italian population sample including people from very young to very old age (centenarians). A total of 1,089 (669 women and 420 men) unrelated individuals from 19 to 109 years, born and residing in northern and central Italy, were subdivided into three age classes defined on the basis of the survival curve constructed using Italian demographic mortality data, and genotyped for the KL-VS allele. We found a significant increase of the heterozygous Klotho genotype in the class of elderly people compared to young controls. On the contrary, no difference was present between centenarians and young controls. Such a non monotonic trajectory is evident only when a large, comprehensive age range is investigated, and is compatible with the hypothesis that this KL-VS heterozygous genotype is favorable for survival in old people, its beneficial effect decreasing thereafter, and becoming no more evident at the extreme ages. Such unusual age-related changes in the Klotho KL-VS genotype frequency is compatible with the hypothesis that alleles and genotypes involved in aging and longevity may exert their biological effect at specific time windows.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Chromosome Disorders / epidemiology*
  • Chromosome Disorders / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Glucuronidase / genetics*
  • Humans
  • Incidence
  • Italy / epidemiology
  • Life Expectancy*
  • Longevity
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Proportional Hazards Models*
  • Risk Assessment / methods
  • Risk Factors
  • Time Factors


  • Glucuronidase
  • klotho protein