• Journal of Life Science
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• v.33 no.9
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• pp.730-735
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• 2023

In the past decade, numerous studies have been carried out to quantify aging with the help of artificial intelligence. Using DNA methylation data, various models have been developed; these are commonly called epigenetic clocks. Epigenetic age acceleration is usually associated with disease conditions. Schizophrenia is a mental illness associated with severe mental and physical stress. This disease leads to high mortality and morbidity rates in young people compared with other psychological disorders. In the past, the research community considered this disease to be related to the accelerated aging hypothesis. In the current study, we wanted to investigate the epigenetic age acceleration changes in schizophrenia patients to obtain epigenetic insights into the disease. To measure the epigenetic age acceleration, we used two different DNA methylation clock models, namely, Horvath clock and Epi clock, as these are pan-tissue models. We utilized 450k array data compatible with both clocks. We found a slower epigenetic acceleration in the patients' samples when we used the Epi clock. We further analyzed the differentially methylated CpG sites between the control and cases and performed pathway enrichment analysis. We found that most of the CpGs are involved in neuronal processes.

• Animal cells and systems
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• v.16 no.1
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• pp.1-10
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• 2012

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

• Journal of Integrative Natural Science
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• v.16 no.3
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• pp.75-80
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• 2023

Bipolar disorder is a mental illness characterized by extreme mood and behavioral swings, such as highs of euphoria and lows of depression. It is a socially significant disorder in which people with the disorder experience intense mood swings and, for those with severe bipolar disorder, it is even difficult leading a normal life. High stress levels in people with mental illness can lead to neuroendocrine disruption, and it is strongly linked to aging. When the neuroendocrine system becomes vulnerable to these mental illnesses and stress, it is likely to accelerate aging. And it's the epigenetic clock that can measure the extent of this accelerated aging. The Epi clock, a pan tissue clock, measures aging through DNA methylation, and the degree of methylation is modified and changed by environmental conditions in the body. Therefore we wanted to check the changes in the epigenetic age of the patients with bipolar disorder. While we found no significant differences in epigenetic age, we did confirm the possibility that people with bipolar disorder have different methylation than normal people. We also found that the EPIC array data fit better on the Epi clock than on the Horvath clock with age-accelerated data from normal people.

• Journal of Integrative Natural Science
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• v.16 no.2
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• pp.61-67
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• 2023

Human body ages differently due to environmental, genetic and pathological factors. DNA methylation patterns also differs depending on various factors such as aging and several other diseases. The aging clock model, which uses these differences to predict age, analyzes DNA methylation patterns, recognizes age-specific patterns, predicts age, and grasps the speed and degree of aging. Aging occurs in everyone and causes various problems such as deterioration of physical ability and complications. Alzheimer's disease is a disease associated with aging and the most common brain degenerative disease. This disease causes various cognitive functions disabilities such as dementia and impaired judgment to motor functions, making daily life impossible. It has been reported that the incidence and progression of this disease increase with aging, and that increased phosphorylation of Aβ and tau proteins, which are overexpressed in this disease and accelerates epigenetic aging. It has also been reported that DNA methylation is significantly increased in the hippocampus and entorhinal cortex of Alzheimer's disease patients. Therefore, we calculated the biological age using the Epi clock, a pan-tissue aging clock model, and confirmed that the epigenetic age of patients suffering from Alzheimer's disease is lower than their actual age. Also, it was confirmed to slow down aging.

• BMB Reports
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• v.52 no.10
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• pp.577-588
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• 2019

DNA methylation at CpG sites is an essential epigenetic mark that regulates gene expression during mammalian development and diseases. Methylome refers to the entire set of methylation modifications present in the whole genome. Over the last several years, an increasing number of reports on brain DNA methylome reported the association between aberrant methylation and the abnormalities in the expression of critical genes known to have critical roles during aging and neurodegenerative diseases. Consequently, the role of methylation in understanding neurodegenerative diseases has been under focus. This review outlines the current knowledge of the human brain DNA methylomes during aging and neurodegenerative diseases. We describe the differentially methylated genes from fetal stage to old age and their biological functions. Additionally, we summarize the key aspects and methylated genes identified from brain methylome studies on neurodegenerative diseases. The brain methylome studies could provide a basis for studying the functional aspects of neurodegenerative diseases.