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Telomeres Increasingly Develop Aberrant Structures in Aging Humans.

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 because of 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. Although 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 life span. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging-associated telomere erosion in humans.

SUBMITTER: Boccardi V

PROVIDER: S-EPMC7176058 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Telomeres Increasingly Develop Aberrant Structures in Aging Humans.

Boccardi Virginia V Cari Luigi L Nocentini Giuseppe G Riccardi Carlo C Cecchetti Roberta R Ruggiero Carmelinda C Arosio Beatrice B Paolisso Giuseppe G Herbig Utz U Mecocci Patrizia P

The journals of gerontology. Series A, Biological sciences and medical sciences 20200101 2

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 because of oth ...[more]

PMID: 30388200

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Dataset Information

Telomeres Increasingly Develop Aberrant Structures in Aging Humans.

Publications

Telomeres Increasingly Develop Aberrant Structures in Aging Humans.

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