Erosion of telomeric 3'-overhangs in white blood cells of aged subjects with high frequency of very short telomeres.
After extended proliferation, cells enter a state of replicative quiescence that is probably due to progressive telomere shortening. It is supposed that changes in telomere structure eventually expose the chromosome ends to undesired recombination events and thus promote cell senescence. The telomeric 3'-overhang is crucial for efficient chromosome capping, but its specific role in telomere shortening and in triggering the senescence program is uncertain. We have addressed this issue by measuring the 3'-overhangs of a human tissue cells aging in vivo. The 3'-overhangs were analyzed in blood samples from 41 individuals aged 91-106 years and 89 individuals ranging from 6 months to 85 years. We found that the overall 3'-overhang length did not significantly change with age, but did, however, find extensively eroded 3'-overhangs in 3 subjects of the 91-106 years cohort and one 61 years old subject affected with Down syndrome. These subjects had 3'-overhang length distributions skewed towards shorter tails, the shortest overall telomere lengths and the highest frequencies of very short telomeres. These data raise the possibility that during ageing very short telomeres with very poor 3'-overhangs can reach a critical point for functional telomeres.
Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy.
Stefano
S
Mattarocci
Ettore
E
D'Ambrosio
Laura
L
Tafaro
Valentina
V
Somma
Giuseppa
G
Zannino
Vincenzo
V
Marigliano
Fiorentina
F
Ascenzioni
Graziella
G
Cimino-Reale
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
D015342:DNA Probes; D004247:DNA