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Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double ap...

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Autores principales: Podolskiy, Dmitriy I., Lobanov, Alexei V., Kryukov, Gregory V., Gladyshev, Vadim N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990632/
https://www.ncbi.nlm.nih.gov/pubmed/27515585
http://dx.doi.org/10.1038/ncomms12157
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author Podolskiy, Dmitriy I.
Lobanov, Alexei V.
Kryukov, Gregory V.
Gladyshev, Vadim N.
author_facet Podolskiy, Dmitriy I.
Lobanov, Alexei V.
Kryukov, Gregory V.
Gladyshev, Vadim N.
author_sort Podolskiy, Dmitriy I.
collection PubMed
description Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer.
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spelling pubmed-49906322016-09-01 Analysis of cancer genomes reveals basic features of human aging and its role in cancer development Podolskiy, Dmitriy I. Lobanov, Alexei V. Kryukov, Gregory V. Gladyshev, Vadim N. Nat Commun Article Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. Nature Publishing Group 2016-08-12 /pmc/articles/PMC4990632/ /pubmed/27515585 http://dx.doi.org/10.1038/ncomms12157 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Podolskiy, Dmitriy I.
Lobanov, Alexei V.
Kryukov, Gregory V.
Gladyshev, Vadim N.
Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title_full Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title_fullStr Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title_full_unstemmed Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title_short Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
title_sort analysis of cancer genomes reveals basic features of human aging and its role in cancer development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990632/
https://www.ncbi.nlm.nih.gov/pubmed/27515585
http://dx.doi.org/10.1038/ncomms12157
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