Key Takeaways & Executive Findings
- •• High glucose induces senescence in HT-22 hippocampal neurons, characterized by reduced cell viability, decreased telomerase activity, and upregulation of senescence markers P53, P21, and P16. • Emodin treatment alleviates high glucose-induced senescence by restoring cell viability, increasing telomerase activity, and downregulating senescence markers. • High glucose downregulates lamin A/C expression, while emodin upregulates lamin A/C, suggesting a potential mechanism for its anti-senescence effect. • Emodin may serve as a therapeutic candidate for diabetic encephalopathy by targeting lamin A/C to mitigate neuronal senescence.
Abstract
BACKGROUND: The occurrence of diabetic encephalopathy may be closely related to neuronal aging, but its underlying molecular mechanism is not fully understood. Therefore, exploring the role of neuronal senescence in diabetic encephalopathy is of great significance for further revealing the pathogenesis of diabetic encephalopathy. OBJECTIVE: To investigate the effect and mechanism of emodin on senescence of HT-22 cells under high glucose conditions. METHODS: HT-22 cells were divided into control group (glucose concentration 25 mmol/L), high glucose group (glucose concentration 55 mmol/L), and high glucose + emodin group (glucose concentration 55 mmol/L, emodin concentration 100 µmol/L) and cultured for 48 h. The growth state of cells in each group was observed under microscope; CCK-8 assay was used to detect cell viability; ELISA was used to detect telomerase reverse transcriptase activity; RT-qPCR and western blot were used to detect the expression of senescence-related proteins P53, P21, and P16; immunofluorescence, RT-qPCR and western blot were used to detect the expression of lamin A/C. RESULTS AND CONCLUSION: Compared with the control group, the high glucose group showed obvious growth inhibition under microscope, characterized by decreased cell number, increased cell volume, and flattened morphology; compared with the high glucose group, the high glucose + emodin group showed significantly increased cell number and more regular morphology. Compared with the control group, cell viability was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, cell viability was significantly increased in the high glucose + emodin group (P < 0.0001). Compared with the control group, telomerase reverse transcriptase activity was significantly decreased in the high glucose group (P < 0.001). Compared with the control group, the expression levels of P53, P21, and P16 were significantly increased in the high glucose group (P < 0.05); compared with the high glucose group, the expression levels of P53, P21, and P16 were significantly decreased in the high glucose + emodin group (P < 0.05). Compared with the control group, the expression level of lamin A/C was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, the expression level of lamin A/C was significantly increased in the high glucose + emodin group (P < 0.05). The results indicate that emodin may slow down the senescence of HT-22 cells induced by high glucose by upregulating the expression of lamin A/C.
1. Introduction
Diabetic encephalopathy, a common severe chronic complication of diabetes, is a neurodegenerative disease closely related to aging [1], characterized by cognitive dysfunction and structural changes in the brain [2-3]. Its pathogenesis is complex and involves multiple factors. Several studies have shown a close link between diabetes and aging, with diabetes accelerating brain aging [4-7]; however, the molecular mechanisms underlying this association remain to be fully explored. High glucose, a major pathological feature of diabetes, imposes multiple challenges on cells, including increased oxidative stress and metabolic disturbances, thereby promoting the accumulation of senescent cells and accelerating cellular senescence [8-10]. Numerous studies have found that high glucose can induce premature aging in various cell types, such as endothelial cells and renal mesangial cells [11-14], but the mechanisms by which high glucose induces cellular senescence are not fully clarified, and whether high glucose directly induces hippocampal neuronal senescence and its mechanisms still lack systematic investigation. In the context of concurrent diabetes and aging, research on diabetes and aging is of great significance for the prevention and treatment of chronic diseases, and many areas warrant in-depth exploration. Finding drugs to improve diabetes-related cognitive aging has important clinical value and social significance.
Aging is a functional decline process that occurs with age, encompassing both organismal and cellular levels. Cellular senescence refers to the irreversible growth arrest of cells (e.g., G0 phase arrest), characterized by loss of proliferative capacity, altered metabolic activity, and changes in secretory phenotype. Cellular senescence is a classic hallmark of aging, occupying a place among the 14 hallmarks of aging published in Cell in April 2025 [8]. Typical features include irreversible cell cycle arrest and abnormal accumulation of senescent cells in tissues. Furthermore, senescent cells can induce local and even systemic chronic inflammation through the secretion of senescence-associated secretory phenotype, thereby forming a 'senescence-inflammatory' vicious cycle that accelerates the aging process.
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Rao Binchan, Xu Yongjie, Xu Mengling, Chen Di, Zhu Liying, Yang Siyuan, Li Xing, Wang Zhengrong, Pan Wei (2026). Role and mechanism of emodin in slowing down the senescence of HT-22 cells induced by high glucose. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21343
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Frequently Asked Questions
What is the role of emodin in high glucose-induced senescence of HT-22 cells?
Emodin alleviates high glucose-induced senescence in HT-22 cells by restoring cell viability, increasing telomerase activity, and downregulating senescence markers P53, P21, and P16, likely through upregulation of lamin A/C expression.
How does high glucose affect lamin A/C expression in HT-22 cells?
High glucose significantly reduces lamin A/C expression in HT-22 cells, which is associated with increased cellular senescence.
What are the key senescence markers examined in this study?
The study examined senescence-related proteins P53, P21, and P16, as well as telomerase reverse transcriptase activity and lamin A/C expression.
What is the potential mechanism by which emodin slows down neuronal senescence?
Emodin may slow down neuronal senescence by upregulating lamin A/C expression, thereby counteracting the downregulation induced by high glucose and mitigating senescence-associated changes.
What is the significance of this study for diabetic encephalopathy treatment?
This study suggests that emodin could be a potential therapeutic agent for diabetic encephalopathy by targeting lamin A/C to prevent or delay neuronal senescence, offering a new avenue for treatment.
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