Whole-genome sequencing analysis of semi-supercentenarians

Elife. 2021 May 4:10:e57849. doi: 10.7554/eLife.57849.


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: ageing; clonal hematopoiesis; genetics; genomics; geroscience; human; longevity; semi-supercentenarians; sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Clonal Hematopoiesis / genetics*
  • Cohort Studies
  • DNA Repair*
  • Female
  • Genetic Background
  • Humans
  • Italy
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Whole Genome Sequencing / methods
  • Whole Genome Sequencing / statistics & numerical data*

Associated data

  • figshare/10.6084/m9.figshare.12367085.v1

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.