Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder-Reference-Cited by-同舟云学术

Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder

Published:2024-01-26 Issue:2 Volume:48 Page:250-259
ISSN:2993-7175
Container-title:Alcohol, Clinical and Experimental Research
language:en
Short-container-title:Alcohol, Clinical and Experimental Research

Author:

Zillich Lea¹²^ORCID,Cetin Metin¹,Hummel Elisabeth M.³,Poisel Eric¹,Fries Gabriel R.⁴,Frank Josef¹,Streit Fabian¹,Foo Jerome C.¹^ORCID,Sirignano Lea¹,Friske Marion M.⁵^ORCID,Lenz Bernd⁶^ORCID,Hoffmann Sabine⁶,Adorjan Kristina⁷⁸,Kiefer Falk⁶,Bakalkin Georgy⁹,Hansson Anita C.⁵,Lohoff Falk W.²^ORCID,Kärkkäinen Olli¹⁰^ORCID,Kok Eloise¹¹¹²¹³,Karhunen Pekka J.¹³¹⁴^ORCID,Sutherland Greg T.¹⁵,Walss‐Bass Consuelo⁴,Spanagel Rainer⁵,Rietschel Marcella¹,Moser Dirk A.³,Witt Stephanie H.¹¹⁶

Affiliation:

1. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany

2. Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda Maryland USA

3. Department of Genetic Psychology, Faculty of Psychology Ruhr Universität Bochum Bochum Germany

4. Louis A. Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USA

5. Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany

6. Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany

7. Department of Psychiatry and Psychotherapy University Hospital, Ludwig Maximilian University of Munich Munich Germany

8. Institute of Psychiatric Phenomics and Genomics, University Hospital Ludwig Maximilian University of Munich Munich Germany

9. Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden

10. School of Pharmacy University of Eastern Finland Kuopio Finland

11. Department of Pathology University of Helsinki Helsinki Finland

12. HUS Diagnostic Center Helsinki University Hospital Helsinki Finland

13. Faculty of Medicine and Health Technology Tampere University Tampere Finland

14. Fimlab Laboratories Ltd., Pirkanmaa Hospital District, and Finnish Cardiovascular Research Centre Tampere Tampere Finland

15. Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia

16. Center for Innovative Psychiatric and Psychotherapeutic Research, Biobank, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany

Abstract

AbstractBackgroundAlcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation‐related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken.MethodsAs markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63–94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates.ResultsThe majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain.ConclusionsThe present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.

Funder

Research Society on Alcoholism

Bundesministerium für Bildung und Forschung

Deutsche Forschungsgemeinschaft

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acer.15241

Reference59 articles.

1. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays

2. Association of Mitochondrial DNA Copy Number With Cardiovascular Disease

3. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions

4. Associations between alcohol use and accelerated biological ageing

5. Accelerated aging with HIV begins at the time of initial HIV infection