Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging

Spano, Luana; Étain, Bruno; Meyrel, Manon; Hennion, Vincent; Gross, Gregory D.; Laplanche, Jean‐Louis; Bellivier, Frank; Marie-Claire, Cynthia

doi:10.1038/s41398-022-01891-4

Cited by 17 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to Köse Çinar (2017), late-stage patients have shorter TL than early-stage patients and controls (Köse Çinar 2017). Spano et al showed that the relatively short telomere length in bipolar patients might be an essential criterion to distinguish patients from healthy individuals (AUC; 0.904) (Spano et al 2022a). When we look at these studies, as in our study, telomere length was found to be short in patients with bipolar disorder.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Analysis of ATPase-6 mtDNA mutations and telomere length in patients with bipolar disorder

Dirican

Özcan

Uzunçakmak

2023

Preprint

View full text Add to dashboard Cite

This study's objective was to analyze ATPase-6 mtDNA mutations and telomere length in patients with bipolar disorder. 37 patients with bipolar disorder and 48 healthy individuals were included in this research. DNA samples of all patients and healthy individuals were isolated. To identify mtDNA mutations in patients, samples were first amplified by PCR, and then Sanger DNA sequencing was performed. RT-PCR method was used for relative telomere length analysis. T112A (m.8860A>G) mutation was detected in all patients (37/37). In addition, T53I (m.8684 C>T) mutations were detected in three patients (3/37) and L156L (m.8994 G>A) and S176N (m.9053 G>A) mutations in one patient each (1/37). Telomere lengths of patients with bipolar disorder were shorter than healthy individuals (p=0.0046). ROC analyses showed that telomere length has a significant diagnostic value for bipolar patients with 94.6% sensitivity and 45.8% specificity (AUC:0.678, 95% CI: 0.568-0.776, p=0.002). There were not statistically significant differences in telomere lengths according to mutation type (p>0.05). Also, there was no relation difference between ATPase-6 mtDNA mutations and telomere length and clinical demographic data (p>0.05). In conclusion, it was shown that patients with bipolar disorder have shorter telomere lengths than healthy individuals. Telomere length may be used as a diagnostic factor. Furthermore, the high frequency of ATPase-6 mtDNA mutations may be part of the genetic background of bipolar disorder. It would be beneficial to support studies with more extensive patient populations to confirm the results we found.

show abstract

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Analysis of ATPase-6 mtDNA mutations and telomere length in patients with bipolar disorder

Dirican

Özcan

Uzunçakmak

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, our study also found a difference in the correlation between GrimAge and chronological age, especially for the earliest age group between BD/non-SA and BD/SA in the replication cohort and between BD/SA and controls in the discovery cohort. This suggests that GrimAgeAccel may already be detected in young individuals with a history of SA, which coincides with previous observation of shorter telomere length and lower mitochondrial DNA copy numbers in a subgroup of young BD individuals [87].…”

Section: (Which Was Not Certified By Peer Review) Preprintsupporting

confidence: 91%

Association between the Epigenetic Lifespan Predictor GrimAge and History of Suicide Attempt in Bipolar Disorder

Lima¹,

Kovács

Mirza

et al. 2022

Preprint

View full text Add to dashboard Cite

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n=50), BD individuals with (n=77, BD/SA) and without (n=67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n=48) and BD/non-SA (n=47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F=5.424, p=0.005), with the highest GrimAgeAccel in BD/SA (p=0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p=0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

show abstract

“…Multiple publications have shown increased mtDNA in maternal circulation and cord blood in pregnancies affected by PE, PE/IUGR, and IUGR [ 50 , 51 ]. Contrarily, the quality of mitochondrial quality and mtDNA copy number is significantly reduced in ageing cells [ 52 , 53 , 54 ]. This study did not provide evidence of increased mtDNA copy numbers in PE, PE associated with IUGR, and IUGR, and based on this surrogate marker of mitochondrial dysfunction, we propose that mitochondrial dysfunction is not a significant contributor to the heterogeneity evident in our study.…”

Section: Discussionmentioning

confidence: 99%

Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence

Manna

McElwain

Maher

et al. 2023

IJMS

View full text Add to dashboard Cite

Premature ageing of the placenta in pregnancy outcomes is associated with the persistent presence of oxidative stress and placental insufficiency reducing its functional capacity. In this study, we investigated cellular senescence phenotypes of pre-eclampsia and IUGR pregnancies by simultaneously measuring several biomarkers of senescence. Maternal plasma and placental samples were collected at term gestation from nulliparous women undergoing pre-labour elective caesarean section with pre-eclampsia without intrauterine growth restriction (PE; n = 5), pre-eclampsia associated with intrauterine growth restriction (n = 8), intrauterine growth restriction (IUGR < 10th centile; n = 6), and age-matched controls (n = 20). Placental absolute telomere length and senescence gene analysis was performed by RTqPCR. The expression of cyclin-dependent kinase inhibitors (p21 and p16) was determined by Western blot. Senescence-associated secretory phenotypes (SASPs) were evaluated in maternal plasma by multiplex ELISA assay. Placental expression of senescence-associated genes showed significant increases in CHEK1, PCNA, PTEN, CDKN2A, and CCNB-1 (p < 0.05) in pre-eclampsia, while TBX-2, PCNA, ATM, and CCNB-1 expression were evident (p < 0.05) and were significantly decreased in IUGR compared with controls. Placental p16 protein expression was significantly decreased in pre-eclampsia only compared with controls (p = 0.028). IL-6 was significantly increased in pre-eclampsia (0.54 pg/mL ± 0.271 vs. 0.3 pg/mL ± 0.102; p = 0.017) while IFN-γ was significantly increased in IUGR (4.6 pg/mL ± 2.2 vs. 2.17 pg/mL ± 0.8; p = 0.002) compared with controls. These results provide evidence of premature senescence in IUGR pregnancies, and while cell cycle checkpoint regulators are activated in pre-eclampsia, the cellular phenotype is one of cell repair and subsequent proliferation rather than progression to senescence. The heterogeneity of these cellular phenotypes highlights the complexity of characterising cellular senescence and may equally be indicative of the differing pathophysiological insults unique to each obstetric complication.

show abstract

Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging

Cited by 17 publications

References 46 publications

WITHDRAWN: Analysis of ATPase-6 mtDNA mutations and telomere length in patients with bipolar disorder

WITHDRAWN: Analysis of ATPase-6 mtDNA mutations and telomere length in patients with bipolar disorder

Association between the Epigenetic Lifespan Predictor GrimAge and History of Suicide Attempt in Bipolar Disorder

Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence

Contact Info

Product

Resources

About