Epigenetic clocks in relapse after a first episode of schizophrenia

Segura, Àlex-González; Prohens, Llucia; Mezquida, Gisela; Amoretti, Sílvia; Bioque, Miquel; Ribeiro, Maria Helena; Gurriarán-Bas, Xaquin; Rementería, Lide; Bergé, Daniel; Rodríguez‐Jiménez, Roberto; Roldán, Alexandra; Pomarol‐Clotet, Edith; Ibáñez, Ángela; Usall, Judith; García-Portilla, María Paz; Cuesta, Manuel J.; Parellada, Mara; González‐Pinto, Ana; Berrocoso, Esther; Bernardo, Miquel; Mas, Sergi; González-Díaz, Jairo M.; Arbelo, Néstor; González-Peñas, Javier; Pina‐Camacho, Laura; Diestre, Alba; Selma, Judit; Zorrilla, Iñaki; López, Purificación; Trabsa, Amira; Monserrat, Clara; Sánchez-Pastor, Luis; Nuñez-Doyle, Aggie; Fatjó‐Vilas, Mar; Sarró, Salvador; Butjosa, Anna; Pardo, Marta; López-Ilundain, Jose M.; Torres, Ana M. Sánchez; Sáiz-Ruiz, Jerónimo; Mangado, Enriqueta Ochoa; RIevero, Olga; De‐la‐Cámara, Concepción; Echevarría, Rafael Segarra; González‐Blanco, Leticia

doi:10.1038/s41537-022-00268-2

Cited by 5 publications

(3 citation statements)

References 66 publications

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“…However, in blood samples one would expect a high correlation between the estimates. 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).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Although age-related epigenome changes in other diseases have been linked to disease recurrence in the past, offering new insight into how biological aging affects the clinical course of disease [133], similar connections in CLL have not been thoroughly documented. Age-related changes to the epigenome and biological clocks may serve as predictive markers for treatment response and, maybe, may influence therapy choice because the disease typically affects older people.…”

Section: Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Aging and Age-Related Epigenetic Drift in the Pathogenesis of Leukemia and Lymphomas: New Therapeutic Targets

Allegra,

Caserta,

Mirabile

et al. 2023

Cells

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One of the traits of cancer cells is abnormal DNA methylation patterns. The idea that age-related epigenetic changes may partially explain the increased risk of cancer in the elderly is based on the observation that aging is also accompanied by comparable changes in epigenetic patterns. Lineage bias and decreased stem cell function are signs of hematopoietic stem cell compartment aging. Additionally, aging in the hematopoietic system and the stem cell niche have a role in hematopoietic stem cell phenotypes linked with age, such as leukemia and lymphoma. Understanding these changes will open up promising pathways for therapies against age-related disorders because epigenetic mechanisms are reversible. Additionally, the development of high-throughput epigenome mapping technologies will make it possible to identify the “epigenomic identity card” of every hematological disease as well as every patient, opening up the possibility of finding novel molecular biomarkers that can be used for diagnosis, prediction, and prognosis.

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“…While these studies demonstrate the risk stratification and prognostic value of epigenetic markers in CLL, the identification of epigenetic features associated with treatment response remains understudied. Although age-related changes to the epigenome in other diseases have previously been associated with disease relapse, providing novel insight of the effect of biological aging on the clinical course of disease [ 21 ], these associations have not been well characterized in CLL. As a disease affecting primarily older individuals, these biological clocks may serve as prognostic features for treatment response, including treatment relapse, and potentially, may influence treatment choice.…”

Section: Introductionmentioning

confidence: 99%

Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age

et al. 2023

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Chronic lymphocytic leukemia (CLL) is a mature B cell neoplasm with a predilection for older individuals. While previous studies have identified epigenetic signatures associated with CLL, whether age-related DNA methylation changes modulate CLL relapse remains elusive. In this study, we examined the association between epigenetic age acceleration and time to CLL relapse in a publicly available dataset. DNA methylation profiling of 35 CLL patients prior to initiating chemoimmunotherapy was performed using the Infinium HumanMethylation450 BeadChip. Four epigenetic age acceleration metrics (intrinsic epigenetic age acceleration [IEAA], extrinsic epigenetic age acceleration [EEAA], PhenoAge acceleration [PhenoAA], and GrimAge acceleration [GrimAA]) were estimated from blood DNA methylation levels. Linear, quantile, and logistic regression and receiver operating characteristic curve analyses were conducted to assess the association between each epigenetic age metric and time to CLL relapse. EEAA (p = 0.011) and PhenoAA (p = 0.046) were negatively and GrimAA (p = 0.040) was positively associated with time to CLL relapse. Simultaneous assessment of EEAA and GrimAA in male patients distinguished patients who relapsed early from patients who relapsed later (p = 0.039). No associations were observed with IEAA. These findings suggest epigenetic age acceleration prior to chemoimmunotherapy initiation is associated with time to CLL relapse. Our results provide novel insight into the association between age-related DNA methylation changes and CLL relapse and may serve has biomarkers for treatment relapse, and potentially, treatment selection.

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Epigenetic clocks in relapse after a first episode of schizophrenia

Cited by 5 publications

References 66 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

Aging and Age-Related Epigenetic Drift in the Pathogenesis of Leukemia and Lymphomas: New Therapeutic Targets

Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age

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