Browsing by Subject "Telomerase"

Now showing 1 - 4 of 4
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    A metabolic signature predicts biological age in mice
    (Wiley Open Access, 2013-02) Tomas-Loba, Antonia; Bernardes de Jesus, Bruno; Mato, Jose M; Blasco, Maria Antonia; Fisiología
    Our understanding of the mechanisms by which aging is produced is still very limited. Here, we have determined the sera metabolite profile of 117 wild-type mice of different genetic backgrounds ranging from 8 to 129 weeks of age. This has allowed us to define a robust metabolomic signature and a derived metabolomic score that reliably/accurately predicts the age of wild-type mice. In the case of telomerase-deficient mice, which have a shortened lifespan, their metabolomic score predicts older ages than expected. Conversely, in the case of mice that overexpress telomerase, their metabolic score corresponded to younger ages than expected. Importantly, telomerase reactivation late in life by using a TERT-based gene therapy recently described by us significantly reverted the metabolic profile of old mice to that of younger mice, further confirming an anti-aging role for telomerase. Thus, the metabolomic signature associated with natural mouse aging accurately predicts aging produced by telomere shortening, suggesting that natural mouse aging is in part produced by presence of short telomeres. These results indicate that the metabolomic signature is associated with the biological age rather than with the chronological age. This constitutes one of the first aging-associated metabolomic signatures in a mammalian organism.
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    Open Access
    Envejecimiento : un vistazo bajo la superficie.
    (Comunidad Autónoma de la Región de Murcia, Consejería de Educación y Cultura, Servicio de Publicaciones., 2024) Aparicio Sánchez, Marta
    Con el avance en las técnicas biomédicas se ha conseguido un aumento de la esperanza de la vida. No obstante, esto lleva consigo una serie de consecuencias y un impacto en el deterioro de nuestro organismo. Por ello, el modelo de pez cebra (Danio reiro) como modelo de investigación, no solo nos abre infinitas puertas para mejorar las condiciones de vida agravadas durante nuestra vejez, sino que también nos ayuda a entender de manera más comprensible las causas que lo provoca. Entre estas causas destaca una inactividad de una enzima presente en los extremos de las estructuras cromosómicas (telomerasa). Por ello, mediante la generación de líneas mutantes y transgénicas de Pez Cebra se pretende analizar su repercusión en el proceso de envejecimiento.
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    Telomerase activity in cancer as a diagnostic and therapeutic target
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Kyo, S.; Takakura, M.; Inoue, M.
    Major advances have been made in understanding the role of telomerase in cellular immortalization and carcinogenesis. Human telomeres undergo progressive shortening with cell division, and critical shortening of telomeres with cellular aging triggers a signal for cells to stop dividing and senesce. Telomerase is an enzyme that adds telomeric-repeated sequences to the ends of human chromosome DNA. Telomerase is active in the vast majority of tumors, but not in normal somatic tissues, and prevents progressive shortening of telomeres with cell division, probably giving tumor cells a growth advantage over normal cells. Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay provided the means to analyze telomerase in a wide variety of tissues. Evidence has been accumulated that this assay may be useful as a potential diagnostic tool for cancer. The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers. The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles. Understanding of such mechanisms might provide insight into molecular basis of human carcinogenesis and contributes to the development of novel cancer gene therapy targeting telomerase.
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    Telomeres and telomerase. A survey about methods and recent advances in cancer diagnostic and therapy
    (Murcia : F. Hernández, 2006) Weise, J.M.; Günes, Ç.
    Since the discovery that telomerase is repressed in most normal human somatic cells but strongly expressed in most human tumours, telomerase emerged as an attractive target for diagnostic, prognostic and therapeutic purposes to combat human cancer. In this review, a synopsis of methods detecting telomerase is presented evaluating their potential for diagnostic and prognostic use. Also, the most promising telomerase therapeutics are discussed in the light of recent advances in the field.