Exp Mol Med.
2006 Dec;38(6):686-693.
Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence
- Affiliations
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- 1Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea. ghpark@korea.ac.kr, kyunglee@korea.ac.kr
- 2Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea
- 3National Rural Resources Development Institute, Suwon 441-853, Korea
- 4Department of Plastic and Reconstructive Surgery, Eulji General Hospital, Eulji University, Seoul 139-231, Korea
- 5Department of Preventive Medicine, College of Medicine, Korea University, Seoul 136-705, Korea
- 6Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 110-746, Korea
Abstract
- The gradual loss of telomeric DNA can contribute to replicative senescence and thus, having longer telomeric DNA is generally considered to provide a longer lifespan. Maintenance and stabilization of telomeric DNA is assisted by binding of multiple DNA-binding proteins, including those involved in double strand break (DSB) repair. We reasoned that declining DSB repair capacity and increased telomere shortening in aged individuals may be associated with decreased expression of DSB repair proteins capable of telomere binding. Our data presented here show that among the DSB repair proteins tested, only the expression of Ku70 and Mre11 showed statistically significant age-dependent changes in human lymphocytes. Furthermore, we found that expressions of Ku70 and Mre11 are statistically correlated, which indicate that the function of Ku70 and Mre11 may be related. All the other DSB repair proteins tested, Sir2, TRF1 and Ku80, did not show any significant differences upon aging. In line with these data, people who live in the regional community (longevity group), which was found to have statistically longer average life span than the rest area, shows higher level of Ku70 expression than those living in the neighboring control community. Taken together, our data show, for the first time, that Ku70 and Mre11 may represent new biomarkers for aging and further suggest that maintenance of higher expression of Ku70 and Mre11 may be responsible for keeping longer life span observed in the longevity group.
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