Telomeres progressively shorten with age, and it has been proposed that critically short and dysfunctional telomeres contribute to aging and aging-associated diseases in humans. For many years it was thought that telomere erosion was strictly a consequence of the "end replication problem", or the inability of replicative polymerases to completely duplicate linear DNA ends. It is becoming increasingly evident, however, that telomere shortening of cultured human cells is also caused due to other replication defects in telomeric repeats, those that cause fragile telomeres and other aberrant telomeric structures that can be detected on metaphase chromosomes. Whether these replication defects contribute to telomere erosion also in human tissues is currently unknown. By analyzing peripheral blood mononuclear cells from a total of 35 healthy subjects ranging in age from 23 to 101 years, we demonstrated that telomeres increasingly display aberrant structures with advancing donor age. While the percentages of fragile telomeres increased only until adulthood, the percentages of chromosomes displaying sister telomere loss and sister telomere chromatid fusions increased consistently throughout the entire human lifespan. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging associated-telomere erosion in humans.

Telomeres Increasingly Develop Aberrant Structures in Aging Humans / V. Boccardi, L. Cari, G. Nocentini, C. Riccardi, R. Cecchetti, C. Ruggiero, B. Arosio, G. Paolisso, U. Herbig, P. Mecocci. - In: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. - ISSN 1079-5006. - :0(2018 Nov 02), pp. 1-6. [Epub ahead of print]

Telomeres Increasingly Develop Aberrant Structures in Aging Humans

C. Riccardi;B. Arosio;
2018

Abstract

Telomeres progressively shorten with age, and it has been proposed that critically short and dysfunctional telomeres contribute to aging and aging-associated diseases in humans. For many years it was thought that telomere erosion was strictly a consequence of the "end replication problem", or the inability of replicative polymerases to completely duplicate linear DNA ends. It is becoming increasingly evident, however, that telomere shortening of cultured human cells is also caused due to other replication defects in telomeric repeats, those that cause fragile telomeres and other aberrant telomeric structures that can be detected on metaphase chromosomes. Whether these replication defects contribute to telomere erosion also in human tissues is currently unknown. By analyzing peripheral blood mononuclear cells from a total of 35 healthy subjects ranging in age from 23 to 101 years, we demonstrated that telomeres increasingly display aberrant structures with advancing donor age. While the percentages of fragile telomeres increased only until adulthood, the percentages of chromosomes displaying sister telomere loss and sister telomere chromatid fusions increased consistently throughout the entire human lifespan. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging associated-telomere erosion in humans.
telomeres; human aging; health
Settore MED/09 - Medicina Interna
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
2-nov-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/602417
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