Deletion of Ku86 causes early onset of senescence in mice PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vogel, H., Lim, D. S., Karsenty, G., Finegold, M., Hasty, P. 1999; 96 (19): 10770-10775

Abstract

DNA double-strand breaks formed during the assembly of antigen receptors or after exposure to ionizing radiation are repaired by proteins important for nonhomologous end joining that include Ku86, Ku70, DNA-PK(CS), Xrcc4, and DNA ligase IV. Here we show that ku86-mutant mice, compared with control littermates, prematurely exhibited age-specific changes characteristic of senescence that include osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci, and age-specific mortality. Cancer and likely sepsis (indicated by reactive immune responses) partly contributed to age-specific mortality for both cohorts, and both conditions occurred earlier in ku86(-/-) mice. These data indicate that Ku86-dependent chromosomal metabolism is important for determining the onset of age-specific changes characteristic of senescence in mice.

View details for DOI 10.1073/pnas.96.19.10770

View details for Web of Science ID 000082574100047

View details for PubMedID 10485901

View details for PubMedCentralID PMC17958