eLife (May 2021)
Whole-genome sequencing analysis of semi-supercentenarians
- Paolo Garagnani,
- Julien Marquis,
- Massimo Delledonne,
- Chiara Pirazzini,
- Elena Marasco,
- Katarzyna Malgorzata Kwiatkowska,
- Vincenzo Iannuzzi,
- Maria Giulia Bacalini,
- Armand Valsesia,
- Jerome Carayol,
- Frederic Raymond,
- Alberto Ferrarini,
- Luciano Xumerle,
- Sebastiano Collino,
- Daniela Mari,
- Beatrice Arosio,
- Martina Casati,
- Evelyn Ferri,
- Daniela Monti,
- Benedetta Nacmias,
- Sandro Sorbi,
- Donata Luiselli,
- Davide Pettener,
- Gastone Castellani,
- Claudia Sala,
- Giuseppe Passarino,
- Francesco De Rango,
- Patrizia D'Aquila,
- Luca Bertamini,
- Nicola Martinelli,
- Domenico Girelli,
- Oliviero Olivieri,
- Cristina Giuliani,
- Patrick Descombes,
- Claudio Franceschi
Affiliations
- Paolo Garagnani
- ORCiD
- 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
- Julien Marquis
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Massimo Delledonne
- Functional Genomics Laboratory, Department of Biotechnology, University of Verona, Verona, Italy
- Chiara Pirazzini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
- Elena Marasco
- Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy
- Katarzyna Malgorzata Kwiatkowska
- ORCiD
- Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
- Vincenzo Iannuzzi
- Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy
- Maria Giulia Bacalini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
- Armand Valsesia
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Jerome Carayol
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Frederic Raymond
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Alberto Ferrarini
- Functional Genomics Laboratory, Department of Biotechnology, University of Verona, Verona, Italy
- Luciano Xumerle
- Functional Genomics Laboratory, Department of Biotechnology, University of Verona, Verona, Italy
- Sebastiano Collino
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Daniela Mari
- Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Beatrice Arosio
- Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy; Geriatric Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Martina Casati
- Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Evelyn Ferri
- Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Daniela Monti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
- Benedetta Nacmias
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Firenze, Italy
- Sandro Sorbi
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Firenze, Italy
- Donata Luiselli
- Department for the Cultural Heritage (DBC), University of Bologna, Ravenna, Italy
- Davide Pettener
- Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy
- Gastone Castellani
- Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
- Claudia Sala
- Department of Physics and Astronomy, University of Bologna, Bologna, Italy
- Giuseppe Passarino
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
- Francesco De Rango
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
- Patrizia D'Aquila
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy
- Luca Bertamini
- 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
- Nicola Martinelli
- Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy
- Domenico Girelli
- Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy
- Oliviero Olivieri
- Department of Medicine, Unit of Internal Medicine, University of Verona, Verona, Italy
- Cristina Giuliani
- ORCiD
- 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
- Patrick Descombes
- Nestlé Research, Société des Produits Nestlé SA, Lausanne, Switzerland
- Claudio Franceschi
- 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
- DOI
- https://doi.org/10.7554/eLife.57849
- Journal volume & issue
-
Vol. 10
Abstract
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.
Keywords
