Correlation between senescence and DNA repair in cells from young and old individuals and in premature aging syndromes.
Cellular aging appears to be related to and perhaps caused by diminished DNA repair. To elucidate direct correlations between DNA repair capacity and senescence various parameters of cellular aging and DNA repair were studied simultaneously. Of special interest are features of DNA repair and senescence in cultured diploid fibroblasts derived either from healthy young or elderly probands as well as from patients suffering from premature senescence syndromes (Werner syndrome, Cockayne syndrome, ataxia telangiectasia and Down syndrome). Here we demonstrate the striking parallelism between reduced maximal lifespan, elevated levels of spontaneous chromosomal breaks, higher incidence of formation of micronuclei, a significant prolongation of cell cycle duration and a diminished reactivation of in vitro injured plasmid after transfection in cells from old individuals and from patients with premature senescence syndromes, suggesting a causal relationship between senescence and DNA damage.
Weirich-Schwaiger
H
H
Institut für Medizinische Biologie und Humangenetik der Universität, Innsbruck, Austria.
Weirich
H G
HG
Gruber
B
B
Schweiger
M
M
Hirsch-Kauffmann
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000503:physiopathology; D002453:Cell Cycle; D002470:Cell Survival; D016922:Cellular Senescence / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002869:Chromosome Aberrations; D003057:Cockayne Syndrome / Q000235:genetics* / Q000503:physiopathology; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004314:Down Syndrome / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D014162:Transfection; D014898:Werner Syndrome / Q000235:genetics* / Q000503:physiopathology
D015500:Chloramphenicol O-Acetyltransferase