Whole-genome sequencing analysis of semi-supercentenarians

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.

Automated summary

People who reach extreme ages have a unique genetic background associated with efficient DNA repair mechanisms, which helps delay aging and protect from cardiovascular events. This genetic trait is characterized by lower mutation load compared to younger individuals, as shown in both germline and somatic mutation patterns.