Whole-genome sequencing analysis of semi-supercentenarians

eLife - Tập 10
Paolo Garagnani1,2,3, Julien Marquis4, Massimo Delledonne5, Chiara Pirazzini6, Elena Marasco7,8, Katarzyna Malgorzata Kwiatkowska9, Vincenzo Iannuzzi1, Maria Giulia Bacalini6, Armand Valsesia4, Jérôme Carayol4, Frédéric Raymond4, Alberto Ferrarini5, Luciano Xumerle5, Sebastiano Collino4, Daniela Mari10, Beatrice Arosio11,12, Martina Casati10, Evelyn Ferri10, Daniela Monti13, Benedetta Nacmias14,15, Sandro Sorbi14,15, Donata Luiselli16, Davide Pettener17, Gastone Castellani9, Claudia Sala18, Giuseppe Passarino19, Francesco De Rango19, Patrizia D’Aquila19, Luca Bertamini20,21, Nicola Martinelli21, Domenico Girelli21, Oliviero Olivieri21, Cristina Giuliani22,23, Patrick Descombes4, Claudio Franceschi24,25,6
1Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy
2Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
3Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
4Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
5Functional Genomics Laboratory, Department of Biotechnology, University of Verona, Verona, Italy
6IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
7Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy
8Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
9Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
10Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
11Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy; Geriatric Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
12Geriatric Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
13Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy.
14Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Firenze, Italy
15IRCCS Fondazione Don Carlo Gnocchi, Firenze, Italy
16Department for the Cultural Heritage (DBC), University of Bologna, Ravenna, Italy
17Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy
18Department of Physics and Astronomy, University of Bologna, Bologna, Italy
19Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
20Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy
21Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy
22Department 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
23School of Anthropology and Museum Ethnography, University of Oxford, Oxford, United Kingdom
24Department of Applied Mathematics and Laboratory of Systems Biology of Aging, Lobachevsky University, Nizhny Novgorod, Russian Federation
25Department of Applied Mathematics and Laboratory of Systems Biology of Aging, Lobachevsky University, Nizhny Novgorod, Russian Federation; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

Tóm tắt

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.

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