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Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics
Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886738/ https://www.ncbi.nlm.nih.gov/pubmed/35864375 http://dx.doi.org/10.1007/s11357-022-00590-8 |
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author | Kananen, Laura Hurme, Mikko Bürkle, Alexander Moreno-Villanueva, Maria Bernhardt, Jürgen Debacq-Chainiaux, Florence Grubeck-Loebenstein, Beatrix Malavolta, Marco Basso, Andrea Piacenza, Francesco Collino, Sebastiano Gonos, Efstathios S. Sikora, Ewa Gradinaru, Daniela Jansen, Eugene H. J. M. Dollé, Martijn E. T. Salmon, Michel Stuetz, Wolfgang Weber, Daniela Grune, Tilman Breusing, Nicolle Simm, Andreas Capri, Miriam Franceschi, Claudio Slagboom, Eline Talbot, Duncan Libert, Claude Raitanen, Jani Koskinen, Seppo Härkänen, Tommi Stenholm, Sari Ala-Korpela, Mika Lehtimäki, Terho Raitakari, Olli T. Ukkola, Olavi Kähönen, Mika Jylhä, Marja Jylhävä, Juulia |
author_facet | Kananen, Laura Hurme, Mikko Bürkle, Alexander Moreno-Villanueva, Maria Bernhardt, Jürgen Debacq-Chainiaux, Florence Grubeck-Loebenstein, Beatrix Malavolta, Marco Basso, Andrea Piacenza, Francesco Collino, Sebastiano Gonos, Efstathios S. Sikora, Ewa Gradinaru, Daniela Jansen, Eugene H. J. M. Dollé, Martijn E. T. Salmon, Michel Stuetz, Wolfgang Weber, Daniela Grune, Tilman Breusing, Nicolle Simm, Andreas Capri, Miriam Franceschi, Claudio Slagboom, Eline Talbot, Duncan Libert, Claude Raitanen, Jani Koskinen, Seppo Härkänen, Tommi Stenholm, Sari Ala-Korpela, Mika Lehtimäki, Terho Raitakari, Olli T. Ukkola, Olavi Kähönen, Mika Jylhä, Marja Jylhävä, Juulia |
author_sort | Kananen, Laura |
collection | PubMed |
description | Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00590-8. |
format | Online Article Text |
id | pubmed-9886738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-98867382023-02-01 Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics Kananen, Laura Hurme, Mikko Bürkle, Alexander Moreno-Villanueva, Maria Bernhardt, Jürgen Debacq-Chainiaux, Florence Grubeck-Loebenstein, Beatrix Malavolta, Marco Basso, Andrea Piacenza, Francesco Collino, Sebastiano Gonos, Efstathios S. Sikora, Ewa Gradinaru, Daniela Jansen, Eugene H. J. M. Dollé, Martijn E. T. Salmon, Michel Stuetz, Wolfgang Weber, Daniela Grune, Tilman Breusing, Nicolle Simm, Andreas Capri, Miriam Franceschi, Claudio Slagboom, Eline Talbot, Duncan Libert, Claude Raitanen, Jani Koskinen, Seppo Härkänen, Tommi Stenholm, Sari Ala-Korpela, Mika Lehtimäki, Terho Raitakari, Olli T. Ukkola, Olavi Kähönen, Mika Jylhä, Marja Jylhävä, Juulia GeroScience Original Article Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00590-8. Springer International Publishing 2022-07-21 /pmc/articles/PMC9886738/ /pubmed/35864375 http://dx.doi.org/10.1007/s11357-022-00590-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Kananen, Laura Hurme, Mikko Bürkle, Alexander Moreno-Villanueva, Maria Bernhardt, Jürgen Debacq-Chainiaux, Florence Grubeck-Loebenstein, Beatrix Malavolta, Marco Basso, Andrea Piacenza, Francesco Collino, Sebastiano Gonos, Efstathios S. Sikora, Ewa Gradinaru, Daniela Jansen, Eugene H. J. M. Dollé, Martijn E. T. Salmon, Michel Stuetz, Wolfgang Weber, Daniela Grune, Tilman Breusing, Nicolle Simm, Andreas Capri, Miriam Franceschi, Claudio Slagboom, Eline Talbot, Duncan Libert, Claude Raitanen, Jani Koskinen, Seppo Härkänen, Tommi Stenholm, Sari Ala-Korpela, Mika Lehtimäki, Terho Raitakari, Olli T. Ukkola, Olavi Kähönen, Mika Jylhä, Marja Jylhävä, Juulia Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title | Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title_full | Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title_fullStr | Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title_full_unstemmed | Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title_short | Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
title_sort | circulating cell-free dna in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886738/ https://www.ncbi.nlm.nih.gov/pubmed/35864375 http://dx.doi.org/10.1007/s11357-022-00590-8 |
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