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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

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Abstract

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.

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Acknowledgments

This work was supported by: the PRRIITT program of the Emilia-Romagna Region (and Fondi Strutturali Obiettivo 2); Italian Ministry of Health Grant “Progetto Finalizzato ≪Studio delle differenze uomo-donna nei meccanismi patogenetici delle malattie cardiovascolari≫“to CF; Roberto and Cornelia Pallotti Legacy for Cancer Research Grants to CF and SS. University of Bologna “Progetti Strategici” 2006 grant (“p53 e patologie non neoplastiche nell’anziano: uno studio multidisciplinare sul ruolo del polimorfismo al codone 72 del gene TP53”) to SS.

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Authors and Affiliations

  1. Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126, Bologna, Italy

    Laura Invidia, Stefano Salvioli, Serena Altilia, Michela Pierini, Maria P. Panourgia & Claudio Franceschi

  2. Interdepartmental Centre “L. Galvani” (C.I.G.), University of Bologna, via S. Giacomo 12, 40126, Bologna, Italy

    Stefano Salvioli & Claudio Franceschi

  3. ER-GenTech Laboratory, via Saragat 1, 44100, Ferrara, Italy

    Stefano Salvioli & Claudio Franceschi

  4. Department of Experimental Pathology and Oncology, University of Florence, V. Morgagni 50, 50134, Florence, Italy

    Daniela Monti

  5. Department of Cell Biology, University of Calabria, 87030, Rende, Italy

    Francesco De Rango & Giuseppe Passarino

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  1. Laura Invidia
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  2. Stefano Salvioli
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  9. Claudio Franceschi
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Correspondence to Claudio Franceschi.

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Invidia, L., Salvioli, S., Altilia, S. et al. 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 11, 67–73 (2010). https://doi.org/10.1007/s10522-009-9229-z

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  • DOI: https://doi.org/10.1007/s10522-009-9229-z

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