Franceschi, Claudio and Bezrukov, Vladyslav and Blanché, Hélène and Bolund, Lars and Christensen, Kaare and De Benedictis, Giovanna and Deiana, Luca and Gonos, Efsthatios and Hervonen, Antti and Yang, Huanning and Jeune, Bernard and Kirkwood, Tom B. L. and Kristensen, Peter and Leon, Alberta and Pelicci, Pier Giuseppe and Peltonen, Leena and Poulain, Michel and Rea, Irene Maeve and Remacle, José and Robine, Jean Marie and Schreiber, Stefan and Sikora, Ewa and Slagboom, Pieternella Eline and Spazzafumo, Liana and Stazi, Maria Antonietta and Toussaint, Olivier and Vaupel, James W. (2007) Genetics of healthy aging in europe. Annals of the New York Academy of Sciences, Vol. 1100 (Biogerontology Mechanisms and Interventions), p. 21-45. eISSN 1749-6632. Article.
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The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing Genomics Institute from China), is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians, and statisticians has been set up. The working plan is to: (a) collect DNA and information on the health status from an unprecedented number of long-lived 90+ sibpairs (n= 2650) and of younger ethnically matched controls (n= 2650) from 11 European countries; (b) perform a genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals); this investigation will be followed by linkage disequilibrium mapping (LD mapping) of the candidate chromosomal regions; (c) study in cases (i.e., the 2650 probands of the sibpairs) and controls (2650 younger people), genomic regions (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in previous studies as possible candidates to harbor longevity genes; (d) genotype all recruited subjects for apoE polymorphisms; and (e) genotype all recruited subjects for inherited as well as epigenetic variability of the mitochondrial DNA (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms, within the framework of centralized databases for phenotypic, genetic, and mtDNA data. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, functional genomics and proteomics, molecular biology, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow (a) to identify gender-specific genes involved in healthy aging and longevity in women and men stratified for ethnic and geographic origin and apoE genotype; (b) to perform a longitudinal survival study to assess the impact of the identified genetic loci on 90+ people mortality; and (c) to develop mathematical and statistical models capable of combining genetic data with demographic characteristics, health status, socioeconomic factors, lifestyle habits.
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