Longevity, Aging and DNA Damage: Investigation of the Role of 53BP1 in the Maintenance of Genomic Stability

1. A comparative analysis in five mammalian species of 53BP1 repair foci and micronuclei expression shows an inverse correlation of these two DNA damage markers: higher level of 53BP1 foci are associated to lower incidence of micronuclei formation. 2. By CRISPR-CAS9 methodology, a 53BP1 knock down model, comparable to the difference observed among species, was reproduced: stable downregulation of 53BP1 is associated to lower survival and increase of micronuclei frequency in response to DNA damage. 3. Spontaneous micronuclei (MN) frequency is inversely proportional to adult body mass. 4. 53BP1 as DNA damage marker for the aging process: increased spontaneous 53BP1 foci level and small decrease of repair efficiency are associated to the increase of chronological age, in human donors.