Additive Effects of Stress and Alcohol Exposure on Accelerated Epigenetic Aging in Alcohol Use Disorder

Jung, Jeesun; McCartney, Daniel L.; Wagner, Josephin; Yoo, Joyce; Bell, Andrew S.; Mavromatis, Lucas A.; Rosoff, Daniel B.; Hodgkinson, Colin A.; Sun, Hui; Schwandt, Melanie L.; Diazgranados, Nancy; Smith, Alicia K.; Michopoulos, Vasiliki; Powers, Abigail; Stevens, Jennifer S.; Bradley, Bekh; Fani, Negar; Walker, Rosie M.; Campbell, Archie; Porteous, David J.; McIntosh, Andrew M.; Horvath, Steve; Marioni, Riccardo E.; Evans, Kathryn; Goldman, David; Lohoff, Falk W.

doi:10.1016/j.biopsych.2022.06.036

Cited by 16 publications

(5 citation statements)

References 44 publications

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“…In recent studies, DNAmTL has been shown to have predictive value for a variety of disease phenotypes, such as HIV (Breen et al, 2022) and schizophrenia (Segura et al, 2022). The results from our study contribute to a growing body of evidence showing that DNAmTL and TL show little agreement and seem to differ in their way of assessing this biological feature (Hastings et al, 2022;Jung et al, 2023;Pearce et al, 2021). It has to be noted that we observed heterogeneity between the cohorts in the meta-analysis.…”

Section: Discussionmentioning

confidence: 53%

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

Zillich,

Cetin,

Hummel

et al. 2024

Alcohol, Clinical and Experimental Research

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BackgroundAlcohol 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.

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Section: Discussionmentioning

confidence: 53%

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

Zillich,

Cetin,

Hummel

et al. 2024

Alcohol, Clinical and Experimental Research

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“…Preconception stress along with prenatal and early post-natal stress and/or alcohol exposure all have the potential for elucidating important sources of variance in outcomes across generations for a number of common disorders including cardiovascular, metabolic, neurological, and developmental disorders. Recently, the additive effects of stress and alcohol use has been reported in which epigenetic aging effects were shown to be increased when both stress and heavy alcohol use were present ( Jung et al, 2023 ). The interaction of stress and alcohol consumption across generations may provide substantial explanatory power in our understanding of disease risk.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, additive effects of stress and alcohol use on epigenetic aging have been reported in humans ( Jung et al, 2023 ). Given the interrelated nature of stress and alcohol use ( Becker, 2017 ; Wittgens et al, 2022 ; Keyes et al, 2012 ) and the heritability of their phenotypes discussed in this review, more cross-generational research is needed to investigate the combinatorial effects of chronic preconception stress and ethanol as well as to dissect the stress-inducing effects of ethanol ( Becker, 2017 ) (and any subsequent epigenetic modifications due to this stress) from epigenetic modifications due to ethanol itself.…”

Section: Integration Of Chronic Preconception Stress and Ethanol Expo...mentioning

confidence: 99%

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Rice,

Gil,

Baratta

et al. 2024

Neurobiology of Stress

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“…These findings provide robust evidence suggesting a causal link between short telomeres and sarcoidosis, while also indicating divergent underlying disease mechanisms in sarcoidosis. Although sarcoidosis is not typically associated with families affected by telomere biology disorders ( 52 ), there are indications that short telomeres may lower the threshold for damage induced by chronic cigarette smoke ( 53 ), obesity ( 54 ), and alcohol ( 55 ). Therefore, while short telomeres may not have a direct causal role in sarcoidosis, they could contribute to the age-related onset of chronic immune-inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis

Zhu,

Hao,

Chen

et al. 2024

Front. Med.

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BackgroundTelomere length, crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored.ObjectiveThis study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study.MethodsWe examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy.ResultsSummary data extracted from GWAS datasets of TL (n = 472,174) and (n = 217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524–0.888, p: 0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR: 0.992, 95% confidence interval: 0.979–1.005, p: 0.2424).ConclusionOur results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitoring. Understanding the critical role of telomere shortening enables more effective focus on diagnosing, treating, and curing sarcoidosis linked to telomeres. Clinical investigations into treatments that enhance TL are warranted.

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Additive Effects of Stress and Alcohol Exposure on Accelerated Epigenetic Aging in Alcohol Use Disorder

Cited by 16 publications

References 44 publications

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

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

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis

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