TY - JOUR
T1 - Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics
AU - Kananen, Laura
AU - Hurme, Mikko
AU - Bürkle, Alexander
AU - Moreno-Villanueva, Maria
AU - Bernhardt, Jürgen
AU - Debacq-Chainiaux, Florence
AU - Grubeck-Loebenstein, Beatrix
AU - Malavolta, Marco
AU - Basso, Andrea
AU - Piacenza, Francesco
AU - Collino, Sebastiano
AU - Gonos, Efstathios S.
AU - Sikora, Ewa
AU - Gradinaru, Daniela
AU - Jansen, Eugene H.J.M.
AU - Dollé, Martijn E.T.
AU - Salmon, Michel
AU - Stuetz, Wolfgang
AU - Weber, Daniela
AU - Grune, Tilman
AU - Breusing, Nicolle
AU - Simm, Andreas
AU - Capri, Miriam
AU - Franceschi, Claudio
AU - Slagboom, Eline
AU - Talbot, Duncan
AU - Libert, Claude
AU - Raitanen, Jani
AU - Koskinen, Seppo
AU - Härkänen, Tommi
AU - Stenholm, Sari
AU - Ala-Korpela, Mika
AU - Lehtimäki, Terho
AU - Raitakari, Olli T.
AU - Ukkola, Olavi
AU - Kähönen, Mika
AU - Jylhä, Marja
AU - Jylhävä, Juulia
N1 - Funding Information:
The Health 2000 Survey was funded by the National Institute for Health and Welfare (THL), the Finnish Centre for Pensions (ETK), the Social Insurance Institution of Finland (KELA), the Local Government Pensions Institution (KEVA) and other organisations listed on the survey website ( https://thl.fi/en/web/thl-biobank/for-researchers/sample-collections/health-2000-and-2011-surveys ).
Funding Information:
Open access funding provided by Karolinska Institute. We also acknowledge the financial support provided by the European Commission through the FP7 large-scale integrating project “European Study to Establish Biomarkers of Human Ageing” (MARK-AGE; grant agreement No.: 200880).
Funding Information:
The Young Finns Study has been financially supported by the Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements: No 848146 for To Aition and grant agreement 755320 for TAXINOMISIS, European Research Council (grant 742927 for MULTIEPIGEN project), Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry.
Funding Information:
This analysis was supported financially by Yrjö Jahnsson Foundation (Grant 20197181) and Juho Vainio Foundation to L. Kananen, and by the Academy of Finland through its funding to the Centre of Excellence in Research of Ageing and Care (CoEAgeCare, grant numbers 326567 and 336670). M. Ala-Korpela was supported by a research grant from the Sigrid Juselius Foundation, Finland. J. Jylhävä was supported by the Swedish Research Council (2018–02077), the Loo & Hans Osterman Foundation and the Strategic Research Program in Epidemiology at Karolinska Institutet.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Biomarker of ageing
KW - Cell-free DNA
KW - Frailty
KW - Health behaviours
KW - Metabolomics
KW - Morbidity
UR - http://www.scopus.com/inward/record.url?scp=85134675413&partnerID=8YFLogxK
U2 - 10.1007/s11357-022-00590-8
DO - 10.1007/s11357-022-00590-8
M3 - Article
AN - SCOPUS:85134675413
SN - 2509-2715
VL - 45
SP - 85
EP - 103
JO - GeroScience
JF - GeroScience
IS - 1
ER -