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Semi-supercentenarians and supercentenarians – people who live to the age of 105 years and beyond – personify healthy aging, having avoided the diseases and concomitant disabilities that many adults experience, such as cardiovascular disease, diabetes, cancer, and cognitive decline. Genetics play key roles in longevity and healthy aging. Findings from a recent study indicate that semi-supercentenarians and supercentenarians have unique genetic profiles characterized by highly efficient DNA repair mechanisms.

DNA repair is a cellular defense mechanism that helps maintain genomic integrity. Research had identified five DNA repair pathways, which are active throughout the varied stages of the cell cycle. Failure of these pathways contributes to genomic instability, a hallmark of many chronic diseases.

The study involved 81 semi-supercentenarians (105 years or older) and supercentenarians (110 years or older) who were matched with 36 healthy adults (average age, 68 years) living in the same regions of Italy. Using blood samples collected from the participants, the investigators conducted whole-genome sequencing to identify genetic differences between the two groups and to create a risk score for cardiovascular disease, the leading cause of death worldwide. They compared their findings with those of a similar recent study.

The authors of the study identified five genetic variants among the participants, some of which are involved in DNA repair, mitochondrial function, and elimination of reactive oxygen species – a driver of inflammation. The participants also had fewer naturally occurring mutations, potentially conferring a protective effect against many chronic diseases. They replicated their findings in the other study.

These data suggest that people who live longer, healthier lives share similar genetic profiles that provide protection against many chronic diseases and promote healthy aging. Learn more about healthy aging in this episode featuring aging expert Dr. Judith Campisi.

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