@article{ZannasArlothCarrilloRoaetal.2015,
  author    = {Zannas, Anthony S. and Arloth, Janine and Carrillo-Roa, Tania and Iurato, Stella and R{\"o}h, Simone and Ressler, Kerry J. and Nemeroff, Charles B. and Smith, Alicia K. and Bradley, Bekh and Heim, Christine and Menke, Andreas and Lange, Jennifer F. and Br{\"u}ckl, Tanja and Ising, Marcus and Wray, Naomi R. and Erhardt, Angelika and Binder, Elisabeth B. and Mehta, Divya},
  title     = {Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling},
  series = {Genome Biology},
  volume    = {16},
  journal   = {Genome Biology},
  number    = {266},
  doi       = {10.1186/s13059-015-0828-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149865},
  year      = {2015},
  abstract  = {Background Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. Results We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 \% (110/353) of these CpGs and transcription in 81.7 \% (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Conclusions Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.},
  language  = {en}
}
@article{VeniaminovaCespuglioChernukhaetal.2020,
  author    = {Veniaminova, Ekaterina and Cespuglio, Raymond and Chernukha, Irina and Schmitt-Boehrer, Angelika G. and Morozov, Sergey and Kalueff, Allan V. and Kuznetsova, Oxana and Anthony, Daniel C. and Lesch, Klaus-Peter and Strekalova, Tatyana},
  title     = {Metabolic, Molecular, and Behavioral Effects of Western Diet in Serotonin Transporter-Deficient Mice: Rescue by Heterozygosity?},
  series = {Frontiers in Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Neuroscience},
  issn      = {1662-453X},
  doi       = {10.3389/fnins.2020.00024},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199813},
  year      = {2020},
  abstract  = {Reduced function of the serotonin transporter (SERT) is associated with increased susceptibility to anxiety and depression and with type-2 diabetes, which is especially true in older women. Preference for a "Western diet" (WD), enriched with saturated fat, cholesterol, and sugars, may aggravate these conditions. In previous studies, decreased glucose tolerance, central and peripheral inflammation, dyslipidemia, emotional, cognitive, and social abnormalities were reported in WD-fed young female mice. We investigated the metabolic, molecular, and behavioral changes associated with a 3-week-long dietary regime of either the WD or control diet in 12-month-old female mice with three different Sert genotypes: homozygous (Slc6a4) gene knockout (Sert\(^{-/-}\): KO), heterozygous (Sert\(^{+/-}\): HET), or wild-type mice (Sert\(^{+/+}\): WT). In the WT-WD and KO-WD groups, but not in HET-WD-fed mice, most of changes induced by the WD paralleled those found in the younger mice, including brain overexpression of inflammatory marker Toll-like receptor 4 (Tlr4) and impaired hippocampus-dependent performance in the marble test. However, the 12-month-old female mice became obese. Control diet KO mice exhibited impaired hippocampal-dependent behaviors, increased brain expression of the serotonin receptors Htr2c and Htr1b, as well as increased Tlr4 and mitochondrial regulator, peroxisome proliferator-activated receptor gamma-coactivator-1a (Ppargc1a). Paradoxically, these, and other changes, were reversed in KO-WD mutants, suggesting a complex interplay between Sert deficiency and metabolic factors as well as potential compensatory molecular mechanisms that might be disrupted by the WD exposure. Most, but not all, of the changes in gene expression in the brain and liver of KO mice were not exhibited by the HET mice fed with either diet. Some of the WD-induced changes were similar in the KO-WD and HET-WD-fed mice, but the latter displayed a "rescued" phenotype in terms of diet-induced abnormalities in glucose tolerance, neuroinflammation, and hippocampus-dependent performance. Thus, complete versus partial Sert inactivation in aged mice results in distinct metabolic, molecular, and behavioral consequences in response to the WD. Our findings show that Sert\(^{+/-}\) mice are resilient to certain environmental challenges and support the concept of heterosis as evolutionary adaptive mechanism.},
  language  = {en}
}