The Genetics of Human Longevity

doi:10.1196/annals.1354.033

^{^a} CIG, Interdepartmental Center "L.Galvani," University of Bologna, Bologna, Italy
^{^b} Department of Experimental Pathology, University of Bologna, Bologna, Italy
^{^c} Department of Experimental Oncology and Pathology, University of Firenze, Firenze, Italy
^{^d} Center for Medical Research, ZMF, University of Tübingen, Tübingen, Germany
^{^e} Department of Cell Biology, University of Calabria, Calabria, Italy
^{^f} Institute of Biological Research & Biotechnology, NHR Foundation, Athens, Greece
^{^g} INRCA, National Institute for Research on Aging, Ancona, Italy

Address for correspondence: Prof. Claudio Franceschi, M.D., CIG – Centro Interdipartimentale "L. Galvani," University of Bologna, Via S. Giacomo, 12, 40126 Bologna, Italy. Voice: +39 051 2094740; fax: +39 051 2094747. e-mail: claudio.franceschi{at}unibo.it

Aging is due to a complex interaction of genetic, epigenetic,and environmental factors, but a strong genetic component appearsto have an impact on survival to extreme ages. In order to identify"longevity genes" in humans, different strategies are now available.In our laboratory, we performed association studies on a varietyof "candidate" polymorphisms in Italian centenarians. Many genes/polymorphismsgave negative results, while others showed a positive associationwith human longevity and a sometimes-positive association withunsuccessful aging (myocardial infarction, Alzheimer's disease,and type 2 diabetes). Results regarding genes involved in inflammation(IL-1 cluster, IL-6, IL-10, TNF- ${alpha}$ , TGF- $beta$ , TLR-4, PPAR ${gamma}$ ), insulin/IGF-1signaling pathway and lipid metabolism (apolipoproteins, CETP,PON1), and oxidative stress (p53, p66^shc) will be described.In addition, a strong role of the interaction between nuclearand mitochondrial genomes (mtDNA haplogroups and the C150T mutation)emerged from our findings. Thus, the genetics of human longevityappears to be quite peculiar in a context where antagonisticpleiotropy can play a major role and genes can have a differentbiological role at different ages.

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