Telomere Length in Fibroblasts and Blood Cells from Healthy Centenarians

Mondello, Chiara; Petropoulou, Chariklia; Monti, Daniela; Gonos, Esftathios S.; Franceschi, Claudio; Nuzzo, Fiorella

doi:10.1006/excr.1999.4398

Cited by 99 publications

(57 citation statements)

References 40 publications

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“…A progressive shortening of telomeres with aging has been reported in different tissues and the TRF shortening rate is in the range of 30 -50 bp per year. 31,32 Telomere shortening may vary according to the type of tissue involved 31 but also according to patient's age at the time of examination. 32 In our current study, we used, as telomere length controls, normal striated muscle from patients aged from 10 -78 years old.…”

Section: Discussionmentioning

confidence: 99%

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Yan

Benhattar

Coindre

et al. 2002

Intl Journal of Cancer

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In a previous study, we showed that telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA expression were undetectable in benign mesenchymal lesions and low-grade soft tissue sarcomas (STSs), but detectable in about 50% of intermediate-/high-grade STSs. We wondered if this lack of TA or hTERT mRNA expression could be related to the tumor sample examined and if there was a relationship between the former 2 parameters and telomere length. Two separate tumor samples from 37 STSs were examined for telomerase activity, using the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA expression, using RT-PCR. Considerable attention has been drawn recently to the regulation of telomere length and telomerase activity in the process of cellular senescence and immortalization. 1,2 Human telomeres are specialized terminal chromosomal structures composed of TTAGGG repeats. Shortening of telomeres has been suggested to represent the mitotic clock of cell cycle; telomere shortening is observed in most dividing somatic cells, leading to cell senescence when reaching a critical level. 1,2 Telomerase, a ribonucleoprotein enzyme that is capable of synthesizing telomeric repeats, plays a pivotal role in the process of telomere length maintenance and cell immortalization. Telomerase activity (TA) has been shown to be expressed in a majority of human carcinomas 1,2 but only few data exist regarding TA in sarcomas. [3][4][5][6][7][8][9] In a previous study, 3 we showed that TA is detectable in only about 50% of intermediate-/high-grade soft tissue sarcomas (STS) and undetectable in benign lesions and low-grade STS. These results are in keeping with those of Schneider Stock et al. detecting TA in 38% (23/60) of their STS 4 and 69% of liposarcomas. 5 A rapid literature survey shows, however, that TA in STS may vary greatly, ranging from 17% 7 to 100% 9 of the cases examined. Some authors also found a positive correlation between TA and tumor aggressiveness in sarcomas 4 and, more specifically, in liposarcomas 5,6,9 whereas others did not. 3 Telomere length has rarely been examined in STS. 5,10 Examining a series of 30 sarcomas, Schneider-Stock et al. 10 showed that telomere TRF length was heterogeneous in this tumor category. Unfortunately, they didn't examine their tumors for TA and, thus, it was not known if telomere length correlated with TA or not. In a further study focusing on liposarcomas only, the same group found a positive correlation between the presence of TA, tumor aggressiveness, high tumor grade and high proliferative activity but not between TA and TRF length. This lack of correlation between TA and TRF length may have several causes including the activation of telomerase-independent mechanism(s) of telomere lengthening referred to as alternative lengthening of telomeres (ALT) 11-13 that seems to occur by means of telomeretelomere recombination. 13,14 In our first study on STS, we observed some degree of heterogeneity in TA expression when examining several, otherwise morphol...

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Section: Discussionmentioning

confidence: 99%

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Yan

Benhattar

Coindre

et al. 2002

Intl Journal of Cancer

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“…Telomere length was analyzed by determining the mean length of the terminal restriction fragments (TRFs) by Southern blotting, as described elsewhere. 20 Briefly, DNA samples were digested with the restriction enzymes HinfI and RsaI (Amersham), resolved on a 0.6% agarose gel, and transferred to a nylon membrane (Hybond N; Amersham). The filters were hybridized with a probe for the telomeric TTAGGG repeats, a mixture of synthetic (TTAGGG)n fragments ranging in size from 100 to 400 bp.…”

Section: Rt-pcr and Competitive Quantitative Rt-pcrmentioning

confidence: 99%

p53 Codon 72 Alleles Influence the Response to Anticancer Drugs in Cells from Aged People by Regulating the Cell Cycle Inhibitor p21^WAF1

Salvioli¹,

Bonafè²,

Barbi³

et al. 2005

Cell Cycle

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“…In fact, telomere shortening, considered the cell internal clock, does not occur in all immune cells and not at the same time (26). A consequence of this molecular and cellular mosaicism could be the presence of a continuous flow of cellular communications enabling the organism to reshape itself in response to the attrition caused by chronic antigen load (16).…”

Section: Discussionmentioning

confidence: 99%

TCR Vβ repertoire in an Italian longeval population including centenarians.

Pennesi

Morellini

Lulli

et al. 2001

AGE

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During the last years, the hypothesis that aging and diseases are two distinct phenomena, and that successful aging is possible for most humans, has been put forward.We studied the TCR VI3 repertoire of T lymphocytes of healthy Iongevals and centenarians as crossing point of genetic predisposition and environmental effects to longevity, using the Spectratyping method.TCR V~I, V~8, and VI~20 were found to be expanded in the Iongeval population, compared with the younger control population. This repertoire can have been shaped by the selective action of particular HLA alleles, or by the clonal expansion of specific T cell clones, able to modulate the immune response to endogenous and exogenous antigens. Moreover, the skewed V~ usage and the clonal expansion seem to be the effects of physiological changes occurring with aging and not pathological signs of malignity.

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Telomere Length in Fibroblasts and Blood Cells from Healthy Centenarians

Cited by 99 publications

References 40 publications

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

p53 Codon 72 Alleles Influence the Response to Anticancer Drugs in Cells from Aged People by Regulating the Cell Cycle Inhibitor p21^WAF1

TCR Vβ repertoire in an Italian longeval population including centenarians.

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Telomere Length in Fibroblasts and Blood Cells from Healthy Centenarians

Cited by 99 publications

References 40 publications

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas

p53 Codon 72 Alleles Influence the Response to Anticancer Drugs in Cells from Aged People by Regulating the Cell Cycle Inhibitor p21WAF1

TCR Vβ repertoire in an Italian longeval population including centenarians.

Contact Info

Product

Resources

About

p53 Codon 72 Alleles Influence the Response to Anticancer Drugs in Cells from Aged People by Regulating the Cell Cycle Inhibitor p21^WAF1