Deletion of Ku86 causes early onset of senescence in mice

Hannes Vogel, Dae Sik Lim, Gerard Karsenty, Milton Finegold, Paul Hasty

Research output: Contribution to journalArticle

299 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10770-10775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number19
DOIs
StatePublished - Sep 14 1999
Externally publishedYes

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