ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Hypermethylation of BDNF and SST Genes in the Orbital Frontal Cortex of Older Individuals: A Putative Mechanism for Declining Gene Expression with Age.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review.Neuroscience and biobehavioral reviews · 2023Pooled it
- Epigenetic Clocks Can Predict Age in the Largemouth Bass-Complex Despite Spatial and Sexual Variation.Evolutionary applications · 2026Article
- Linking Age Changes in Human Cortical Microcircuits to Impaired Brain Function and EEG Biomarkers.Aging cell · 2026Article
- Association between plant-based dietary patterns and dementia among Chinese older adults.Frontiers in nutrition · 2025Article
- Comparing the effect of plasma therapy with estradiol valerate in motor and cognitive behavioral disorders in ovariectomized old rats: Behavioral, biochemical, and protein expression.Iranian journal of basic medical sciences · 2025Article
- Article
- Roles of physical exercise in neurodegeneration: reversal of epigenetic clock.Translational neurodegeneration · 2021Review
- Aging biomarkers and the brain.Seminars in cell & developmental biology · 2021Review
- Reversal of Age-Related Neuronal Atrophy by α5-GABAA Receptor Positive Allosteric Modulation.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Turning the 'Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex.Frontiers in behavioral neuroscience · 2020Article
- AgeGuess, a Methylomic Prediction Model for Human Ages.Frontiers in bioengineering and biotechnology · 2020Article
- Early Manifestations of Brain Aging in Mice Due to Low Dietary Folate and Mild MTHFR Deficiency.Molecular neurobiology · 2019Article
- DNA methylation in the human frontal cortex reveals a putative mechanism for age-by-disease interactions.Translational psychiatry · 2019Article
- Comprehensive functional genomic resource and integrative model for the human brain.Science (New York, N.Y.) · 2018Article
- DNA methylation as a putative mechanism for reduced dendritic spine density in the superior temporal gyrus of subjects with schizophrenia.Translational psychiatry · 2017Article
- DNA methylation evidence against the accelerated aging hypothesis of schizophrenia.NPJ schizophrenia · 2017Article
- The Role of BDNF in Age-Dependent Changes of Excitatory and Inhibitory Synaptic Markers in the Human Prefrontal Cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity.Molecular oncology · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Expression of brain-derived neurotrophic factor (BDNF) and somatostatin (SST) mRNAs in the brain decreases progressively and robustly with age, and lower BDNF and SST expression in the brain has been observed in many brain disorders. BDNF is known to regulate SST expression; however, the mechanisms underlying decreased expression of both genes are not understood. DNA methylation (DNAm) is an attractive candidate mechanism. To investigate the contribution of DNAm to the age-related decline in BDNF and SST expression, the Illumina Infinium HumanMethylation450 Beadchip Array was used to quantify DNAm of BDNF (26 CpG loci) and SST (9 CpG loci) in the orbital frontal cortices of postmortem brains from 22 younger (age <42 years) and 22 older individuals (age >60 years) with known age-dependent BDNF and SST expression differences. Relative to the younger individuals, 10 of the 26 CpG loci in BDNF and 8 of the 9 CpG loci in SST were significantly hypermethylated in the older individuals. DNAm in BDNF exons/promoters I, II, and IV negatively correlated with BDNF expression (r=-0.37, p<0.05; r=-0.40, p<0.05; r=-0.24, p=0.07), and DNAm in SST 5' UTR and first exon/intron negatively correlated with SST expression (r=-0.48, p<0.01; r=-0.63, p<0.001), respectively. An expanded set of BDNF- and GABA-related genes exhibited similar age-related changes in DNAm and correlation with gene expression. These results suggest that DNAm may be a proximal mechanism for decreased expression of BDNF, SST, and other BDNF- and GABA-related genes with brain aging and, by extension, for brain disorders in which their expression is decreased.
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