Work

Deletion of Ku86 causes early onset of senescence in mice

Year: 1999

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.96.19.10770

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

Institution: Baylor College of Medicine

Language: English

Topic: Genetics, Aging, and Longevity in Model Organisms

Subfield: Aging

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute