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The EU-Integrated Project GEHA (GEnetics of Healthy Aging)
a C.I.G.—Interdepartmental Centre "L.Galvani," University of Bologna, Via S. Giacomo 12, 40126 Bologna, Italy b Institute of Gerontology, 04114 Kiev, Ukraine c Centre Polymorphisme Humaine, Fondation Jean Dausset, 75010 Paris, France d Beijing Genomics Institute, Chinese Academy of Sciences, 101300 Beijing, China e Institute of Public Health, University of Southern Denmark, 5000 Odense C, Denmark f University of Calabria, 87030 Rende, Italy g University of Sassari, 07100 Sassari, Italy h National Hellenic Research Foundation, GR-11635 Athens, Greece i Tampere School of Public Health, University of Tampere, 33015 Tampere, Finland j School of Clinical Medical Sciences, Gerontology "Henry Wellcome," University of Newcastle upon Tyne, NE4 6BE Newcastle upon Tyne, United Kingdom k University of Aarhus, 8000 Aarhus C, Denmark l Research & Innovation Soc.Coop. a r.l., 35136 Padova, Italy m IFOM—Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milano, Italy n National Public Health Institute, 00251 Helsinki, Finland o Research Centre of Demographic Management for Public Administrations, UCL—GéDAP, 1348-Louvain-la-Neuve, Belgium p The Queen's University Belfast, BT 9 7BL Belfast, United Kingdom q Eppendorf Array Technologies, SA—EAT Research and Development, 5000 Namur, Belgium r University of Montpellier, Val d'Aurelle Cancer Research Center, 34298 Montpellier, France s Kiel Center for Functional Genomics, University Hospital Schleswig Holstein, 24105 Kiel, Germany t Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland u Leiden University Medical Centre, Leiden, the Netherlands v INRCA—Italian National Research Centre on Aging, 60121 Ancona, Italy w Istituto Superiore di Sanità, 00161 Rome, Italy x Facultés Universitaire Notre Dame de la Paix, B-5000 Namur, Belgium y Max Planck Institute for Demographic Research, 8057 Rostock, Germany
Key Words: longevity • genetics • mitochondrial DNA • centenarians • aging
Address for correspondence: Claudio Franceschi, C.I.G.—Interdepartmental Centre "L.Galvani," University of Bologna, Via S. Giacomo 12, 40126 Bologna, Italy. Voice: +39-051-2094743; fax: +39-051-2094768. claudio.franceschi{at}unibo.it
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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