• 생명과학회지
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• 제33권9호
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• pp.730-735
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• 2023

지난 10년 동안 인공지능의 도움으로 노화를 정량화하기 위한 수많은 연구가 수행되었다. DNA 메틸화 데이터를 사용하여 다양한 모델이 개발되었으며 흔히 후성유전학적 시계라고 불린다. 후성유전학적 나이 가속화는 일반적으로 질병 상태와도 주로 연관이 있어 보인다. 조현병은 가속 노화 가설과 관련있는 정신질병으로 심각한 정신적, 신체적 스트레스를 동반한다. 다른 심리 질환과 비교했을 때 이 질병은 젊은 사람들에서 높은 사망률과 질병률을 유발한다. 과거 연구에서는 이 질병이 가속 노화 가설과 연관있다고 알려져 있었다. 이번 연구에서는 조현병 환자의 후성유전학적 나이 가속도 변화를 통해 질병에 대한 후성유전학적 통찰을 얻고자 하였다. 후성유전학적 나이 가속화를 측정하기 위해 두 가지 다른 DNA 메틸화 시계 모델을 사용했으며 이는 범조직 모델인 Horvath clock과 Epi clock을 사용하였다. 우리는 Horvath clock과 Epi clock이 모두 호환되는 450k 어레이 데이터를 사용하였다. 그 결과, Epi clock을 사용했을 때 환자샘플에서 후성유전학적 나이 가속화가 더 느리다는 것을 발견했다. Epi clock이 질병으로 인한 DNA 메틸화 변화를 잘 감지해낼 수 있음을 알아내었다. 또한 Epi clock에서 대조군과 환자군에서 차등적으로 메틸화된 CpG 부위를 분석하고 경로 농축 분석을 수행한 결과, 대부분의 CpG가 신경 세포 과정에 관여한다는 사실을 발견했다.

• Animal cells and systems
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• 제16권1호
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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.

• 통합자연과학논문집
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• 제16권3호
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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.

• 통합자연과학논문집
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• 제16권2호
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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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• 제52권10호
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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.