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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

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
Katso/Avaa
s11357-022-00590-8.pdf (1.701Mb)
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SPRINGER
doi:10.1007/s11357-022-00590-8
URI
https://link.springer.com/article/10.1007/s11357-022-00590-8
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022091258656
Tiivistelmä

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.

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