TY - JOUR TI - Whole-genome sequencing analysis of semi-supercentenarians AU - Garagnani, Paolo AU - Marquis, Julien AU - Delledonne, Massimo AU - Pirazzini, Chiara AU - Marasco, Elena AU - Kwiatkowska, Katarzyna Malgorzata AU - Iannuzzi, Vincenzo AU - Bacalini, Maria Giulia AU - Valsesia, Armand AU - Carayol, Jerome AU - Raymond, Frederic AU - Ferrarini, Alberto AU - Xumerle, Luciano AU - Collino, Sebastiano AU - Mari, Daniela AU - Arosio, Beatrice AU - Casati, Martina AU - Ferri, Evelyn AU - Monti, Daniela AU - Nacmias, Benedetta AU - Sorbi, Sandro AU - Luiselli, Donata AU - Pettener, Davide AU - Castellani, Gastone AU - Sala, Claudia AU - Passarino, Giuseppe AU - De Rango, Francesco AU - D'Aquila, Patrizia AU - Bertamini, Luca AU - Martinelli, Nicola AU - Girelli, Domenico AU - Olivieri, Oliviero AU - Giuliani, Cristina AU - Descombes, Patrick AU - Franceschi, Claudio A2 - Tyler, Jessica K A2 - Suh, Yousin A2 - Shuldiner, Alan R VL - 10 PY - 2021 DA - 2021/05/04 SP - e57849 C1 - eLife 2021;10:e57849 DO - 10.7554/eLife.57849 UR - https://doi.org/10.7554/eLife.57849 AB - 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. KW - longevity KW - ageing KW - clonal hematopoiesis KW - sequencing KW - geroscience KW - semi-supercentenarians JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -