Heat-Shock Protein 70 Genes and Human Longevity A View from Denmark RIPUDAMAN SINGH, a STEEN KØLVRAA, b PETER BROSS, c KAARE CHRISTENSEN, d NIELS GREGERSEN, c QIHUA TAN, e UFFE BIRK JENSEN, a,h HANS EIBERG, f AND SURESH I. S. RATTAN g a Department of Human Genetics, University of Aarhus, Aarhus, Denmark b Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark c Research Unit for Molecular Medicine, Aarhus University Hospital and Faculty of Health Sciences, Skejby Hospital, Aarhus, Denmark d Institute of Public Health, University of Southern Denmark, Odense, Denmark e Odense University Hospital, KKA, Department of Clinical Biochemistry and Genetics, Odense, Denmark f Panum Institut, Copenhagen, Denmark g Department of Molecular Biology, University of Aarhus, Aarhus, Denmark h Department of Clinical Genetics, University of Aarhus, Aarhus, Denmark ABSTRACT: We have studied the association of three single nucleotide polymorphisms (SNPs) present in the three HSP70 (heat-shock protein) genes on 6p21 with human longevity. The availability of biological sam- ples from various population cohorts in Denmark has given us the op- portunity to try novel methods of gene association with human longevity. A significant association of one haplotype with male longevity was ob- served. Furthermore, a significant difference in the survival of the car- riers of the different genotypes in females was observed. We also found an age-dependant decline in the ability of peripheral blood mononuclear cells to respond to heat stress in terms of Hsp70 induction. KEYWORDS: human longevity; aging; heat-shock proteins; heat-shock response; gene association; linkage disequilibrium Address for correspondence: Ripudaman Singh, Department of Human Genetics, Bartholin Building, University of Aarhus, Aarhus C. Denmark. Voice: +45-8942-1682; fax: +45-8612-3173. e-mail: singh@humgen.au.dk Ann. N.Y. Acad. Sci. 1067: 301–308 (2006). C  2006 New York Academy of Sciences. doi: 10.1196/annals.1354.040 301