2006
DOI: 10.1038/emm.2006.81
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Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence

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 tel… Show more

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Cited by 77 publications
(64 citation statements)
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“…As rats age Ku levels diminish in the testis and Ku70 or Ku80 levels are differentially expressed in various tissues (Um et al, 2003). Similarly as humans age, Ku nuclear localization and DNA binding is impaired in blood mononuclear cells (Doria et al, 2004;Frasca et al, 1999) and Ku70, but not Ku80, levels decline in lymphocytes (Ju et al, 2006). By correlation, Ku levels decline and their cellular distribution is altered as human fibroblasts approach senescence (Seluanov et al, 2007b).…”
Section: Pathways That Repair or Suppress Dna Dsbsmentioning
confidence: 99%
“…As rats age Ku levels diminish in the testis and Ku70 or Ku80 levels are differentially expressed in various tissues (Um et al, 2003). Similarly as humans age, Ku nuclear localization and DNA binding is impaired in blood mononuclear cells (Doria et al, 2004;Frasca et al, 1999) and Ku70, but not Ku80, levels decline in lymphocytes (Ju et al, 2006). By correlation, Ku levels decline and their cellular distribution is altered as human fibroblasts approach senescence (Seluanov et al, 2007b).…”
Section: Pathways That Repair or Suppress Dna Dsbsmentioning
confidence: 99%
“…XRCC5 and XRCC6 encode for the ku80 and ku70 proteins, respectively, which form the Ku heterodimer. Alterations of this complex have been related to the decreased DNA repair capacity in the elderly (Doria et al 2004;Ju et al 2006;Seluanov et al 2007). However, according to our results, the methylation changes observed in these two genes during aging seems to be not associated with an increase of translocations frequency.…”
Section: Discussionmentioning
confidence: 99%
“…In animals, the efficiency of NHEJ was reduced over 4-fold in presenescent and senescent cells relative to young cells, indicating that DNA end joining becomes less efficient and more error prone in senescent cells (Seluanov et al, 2004). The level of Ku70 has been shown to decline markedly in the testes of aging rats (Um et al, 2003) and lymphocytes from aging human donors (Ju et al, 2006). Also, in a recent publication, a 50% reduction in the level of KU70 and KU80 proteins in senescent human fibroblasts was observed .…”
Section: Changes In Mismatch Repair May Be Responsible For An Age-depmentioning
confidence: 99%