To Stay Happy, Keep Your SIRT1 Active

      Depression is one of the most common psychiatric disorders and a major cause of disability that affects almost 350 million people worldwide. Common symptoms include depressed mood, persistent anxiety, loss of interest or pleasure in hobbies, feelings of hopelessness, suicidal thoughts, and reduced motivation. Antidepressant drugs often take weeks or even months to reach therapeutic levels and may result in exacerbated symptoms. The pathophysiological cause of depression has not been clearly identified; however, researchers are actively investigating the molecular pathways that contribute to major depressive disorder in human subjects and examining the basis of stress sensitivity and resilience in rodent subjects. One underlying mechanism may be epigenetic, involving the long-lasting regulation of gene expression via histone modification, DNA modification, and chromatin remodeling. Epigenetic enzymes have been linked to various pathophysiological conditions, including depression (
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      Epigenetics of the depressed brain: Role of histone acetylation and methylation.
      ). Sirtuin 1 (SIRT1), a lysine deacetylase, has been extensively studied for its connection to depression, but the specific role of SIRT1 remains controversial. Deciphering the molecular pathways by which SIRT1 may lead to depressed behavior will provide valuable information from a therapeutic perspective.
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      Linked Article

      • Hippocampal Sirtuin 1 Signaling Mediates Depression-like Behavior
        Biological PsychiatryVol. 80Issue 11
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          Although depression is the leading cause of disability worldwide, its pathophysiology is poorly understood. Recent evidence has suggested that sirtuins (SIRTs) play a key role in cognition and synaptic plasticity, yet their role in mood regulation remains controversial. Here, we aimed to investigate whether SIRT function is associated with chronic stress-elicited depression-like behaviors and neuronal atrophy.
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