Deletion of Ku86 causes early onset of senescence in mice

H Vogel, DS Lim, G Karsenty… - Proceedings of the …, 1999 - National Acad Sciences
H Vogel, DS Lim, G Karsenty, M Finegold, P Hasty
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
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-PKCS, 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 …
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-PKCS, 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.
National Acad Sciences