Whole-genome sequencing analysis of semi-supercentenarians

eLife

Vincenzo Iannuzzi¹  Donata Luiselli²  Davide Pettener³  Cristina Giuliani⁴  Giuseppe Passarino⁵  Francesco De Rango⁵  Patrizia D'Aquila⁵  Daniela Monti⁶  Katarzyna Malgorzata Kwiatkowska⁷  Gastone Castellani⁷  Elena Marasco⁸  Paolo Garagnani⁹  Luca Bertamini^1,10  Claudio Franceschi^1,11  Oliviero Olivieri^1,12  Nicola Martinelli^1,12  Domenico Girelli^1,12  Benedetta Nacmias^1,13  Sandro Sorbi^1,13  Claudia Sala^1,14  Evelyn Ferri^1,15  Daniela Mari^1,15  Martina Casati^1,15  Beatrice Arosio^1,16  Luciano Xumerle^1,17  Massimo Delledonne^1,17  Alberto Ferrarini^1,17  Maria Giulia Bacalini^1,18  Chiara Pirazzini^1,18  Armand Valsesia^1,19  Frederic Raymond^1,19  Sebastiano Collino^1,19  Julien Marquis^1,19  Jerome Carayol^1,19  Patrick Descombes^1,19 

[1] Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy;Department for the Cultural Heritage (DBC), University of Bologna, Ravenna, Italy;Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy;Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy;School of Anthropology and Museum Ethnography, University of Oxford, Oxford, United Kingdom;Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy;Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy;Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy;Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden;Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy;Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy;Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy;Department of Applied Mathematics and Laboratory of Systems Biology of Aging, Lobachevsky University, Nizhny Novgorod, Russian Federation;Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy;Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy;IRCCS Fondazione Don Carlo Gnocchi, Firenze, Italy;Department of Physics and Astronomy, University of Bologna, Bologna, Italy;Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy;Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy;Geriatric Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy;Functional Genomics Laboratory, Department of Biotechnology, University of Verona, Verona, Italy;IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy;Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland;

关键词: longevity;    ageing;    clonal hematopoiesis;    sequencing;    geroscience;    semi-supercentenarians;    Human;   

DOI  :  10.7554/eLife.57849

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

【 授权许可】

CC BY