Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence.
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.
Ju
Yeun-Jin
YJ
Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.
Lee
Kee-Ho
KH
Park
Jeong-Eun
JE
Yi
Yong-Su
YS
Yun
Mi-Yong
MY
Ham
Yong-Ho
YH
Kim
Tae-Jin
TJ
Choi
Hyun Mi
HM
Han
Gwi Jung
GJ
Lee
Jong-Hoon
JH
Lee
Juneyoung
J
Han
Jong Seol
JS
Lee
Kyung-Mi
KM
Park
Gil-Hong
GH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D034961:Antigens, Nuclear / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D008136:Longevity; D000076228:MRE11 Homologue Protein; D008875:Middle Aged; D016615:Telomere / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D004247:DNA; D000076228:MRE11 Homologue Protein; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen