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 NacmiasSandro 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournaleLife
Volume10
DOIs
Publication statusPublished - May 4 2021

Keywords

  • ageing
  • clonal hematopoiesis
  • genetics
  • genomics
  • geroscience
  • human
  • longevity
  • semi-supercentenarians
  • sequencing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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