Life sciences最新文献

{"title":"Nicotinamide riboside promoted cardiac energetics and alleviated doxorubicin-induced cardiotoxicity via SIRT1/ERRα signal in human pluripotent stem cells-derived cardiomyocytes","authors":"Rui Wang ,&nbsp;Hua Zhang ,&nbsp;Qin Yi ,&nbsp;Yun Peng Wang ,&nbsp;Hao Xu ,&nbsp;Bin Tan ,&nbsp;Jing Zhu","doi":"10.1016/j.lfs.2025.123685","DOIUrl":"10.1016/j.lfs.2025.123685","url":null,"abstract":"<div><div>Doxorubicin is an antineoplastic chemotherapeutic drug that causes cardiotoxicity with energetics impairment and oxidative stress. Nicotinamide ribose (NR) is the precursor of NAD+ and has demonstrated beneficial effects in several animal models of cardiovascular disease. This study aimed to test the role and mechanism of nicotinamide ribose on human induced pluripotent stem cell-differentiated cardiomyocytes (HiPSCs-CMs) under normal and doxorubicin-treated states. We found that NR increased mitochondrial fusion and integrity in HiPSCs-CMs, promoted mitochondrial oxidative phosphorylation levels and ATP output, and increased ERRα expression. Inhibition of SIRT1 reversed the beneficial effects of NR. Protein-protein docking and immunoprecipitation showed that SIRT1 may bind directly to ERRα and regulates ERRα expression. Agonism of SIRT1 shows a facilitating effect on mitochondrial energetics, an effect that is counteracted by inhibitors of ERRα. Furthermore, NR promotes mitochondrial energetics via SIRT1/ERRα in doxorubicin-induced cardiac cytotoxicity, reduces cardiomyocyte oxidative stress injury, and attenuates apoptosis. Our findings reveal beneficial effects of nicotinamide ribose on HiPSCs-CMs under normal or disease conditions. In conclusion, our study provides the basis for advancing the clinical translation of nicotinamide ribose into the clinic.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123685"},"PeriodicalIF":5.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the double-edged role of cellular senescence in chronic liver disease for new treatment approaches","authors":"Yiwen Yang ,&nbsp;Qun Cai ,&nbsp;Mingyan Zhu ,&nbsp;Jianning Rong ,&nbsp;Xudong Feng ,&nbsp;Ke Wang","doi":"10.1016/j.lfs.2025.123678","DOIUrl":"10.1016/j.lfs.2025.123678","url":null,"abstract":"<div><div>Cellular senescence is a fundamental yet complex defense mechanism that restricts excessive proliferation, maintains cellular homeostasis under various stress conditions—such as oncogenic activation and inflammation—and serves as a dynamic stress response program involved in development, aging, and immunity. Its reversibility depends on essential maintenance components. Cellular senescence is a “double-edged sword”: on one hand, it limits the malignant proliferation of damaged cells, thereby preventing tumor development. However, by retaining secretory functions, senescent cells can also induce persistent changes in the microenvironment and disrupt homeostasis, leading to tissue inflammation, fibrosis, and carcinogenesis. Senescence plays a critical role in the pathogenesis of various chronic liver diseases, including chronic viral hepatitis, liver fibrosis, and hepatocellular carcinoma. It exerts a dual influence by facilitating immune evasion and inflammation in chronic viral hepatitis, modulating hepatic stellate cell activity in fibrosis, and reshaping the tumor microenvironment to accelerate hepatocarcinogenesis. This article reviews the characteristics of cellular senescence and its role in the pathogenesis of these chronic liver diseases while exploring potential treatment and prevention strategies. The aim is to provide a comprehensive reference for future clinical and research investigations into chronic liver disease.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123678"},"PeriodicalIF":5.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of specific gut microbes and their therapeutic potential in ameliorating systemic lupus erythematosus in a mouse model","authors":"Ji-Seon Ahn ,&nbsp;Ye-Been Lee ,&nbsp;Eui-Jeong Han ,&nbsp;Yu-Jin Choi ,&nbsp;Da-Hye Kim ,&nbsp;Seung Ki Kwok ,&nbsp;Hyung-Kyoon Choi ,&nbsp;Hea-Jong Chung","doi":"10.1016/j.lfs.2025.123684","DOIUrl":"10.1016/j.lfs.2025.123684","url":null,"abstract":"<div><h3>Aims</h3><div>The gut microbiome significantly influences autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to characterize the gut microbiome and metabolome in SLE and evaluate the therapeutic potential of specific microbial supplementation in MRL/<em>lpr</em> mice.</div></div><div><h3>Materials and methods</h3><div>MRL/<em>lpr</em> mice, a well-established model for SLE, were used to analyze gut microbiome changes before and after SLE symptom onset. 16S rRNA sequencing and GC–MS-based metabolic profiling were performed to identify key microbial species and associated metabolites. Selected microbes were supplemented in MRL/<em>lpr</em> mice for 10 weeks, and their effects on SLE symptoms and Th17/Treg balance were evaluated.</div></div><div><h3>Key findings</h3><div><em>Eisenbergiella massiliensis</em>, <em>Lacrimispora saccharolytica</em>, and <em>Hungatella xylanolytica</em> were significantly decreased in MRL/<em>lpr</em> mice following the onset of SLE symptoms. These microbes were strongly correlated with specific metabolites, including 5-cholestanol, cholesterol, <em>p</em>-cresol, and indole. Supplementation with these microbes alleviated SLE symptoms and modulated the Th17/Treg balance.</div></div><div><h3>Significance</h3><div>This study highlights the critical role of gut microbiota in immune regulation and SLE symptom relief. Targeted microbial supplementation may serve as a novel therapeutic strategy for managing SLE.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"374 ","pages":"Article 123684"},"PeriodicalIF":5.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2,3,7,8-tetrachlorodibenzofuran modulates intestinal microbiota and tryptophan metabolism in mice","authors":"Hanxiao Shen ,&nbsp;Ding Wang ,&nbsp;Yuxin Huang ,&nbsp;Yueying Yang ,&nbsp;Shuqi Ji ,&nbsp;Wei Zhu ,&nbsp;Qing Liu","doi":"10.1016/j.lfs.2025.123679","DOIUrl":"10.1016/j.lfs.2025.123679","url":null,"abstract":"<div><div>Persistent organic pollutants (POPs) are known to disrupt gut microbiota composition and host metabolism, primarily through dietary exposure. In this study, we investigate the impact of 2,3,7,8-tetrachlorodibenzofuran (TCDF) on gut microbiota and host metabolic processes. RNA-seq analysis revealed that TCDF exposure significantly affected tryptophan metabolism, lipid metabolic pathways, and immune system function. Metagenomic and metabolomic analyses further showed that TCDF reduced the abundance of <em>Mucispirillum schaedleri</em> and levels of two key tryptophan metabolites, indole-3-carboxaldehyde (3-IAld) and Indole acrylic acid (IA). Supplementation with 3-IAld and IA alleviated TCDF-induced liver toxicity in mouse, as evidenced by reduced <em>Cyp1a1</em> expression, and mitigated intestinal inflammation, reflected by lower pro-inflammatory cytokines (<em>Ifn-γ</em> and <em>Il-1β</em>) in the colon. Additionally, 3-IAld and IA supplementation enhanced intestinal barrier function, as demonstrated by increased Mucin 2 (MUC2) expression in the gut mucosa of mouse. These findings suggest that TCDF exposure disrupts the gut microbiome and host metabolic balance, and highlight the potential therapeutic role of tryptophan-derived metabolites in mitigating environmental pollutant-induced damage.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123679"},"PeriodicalIF":5.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR40 signaling in agouti-related peptide neurons mediates fat preference","authors":"Yueping Ge ,&nbsp;Huidong Zhan ,&nbsp;Shanshan Wu ,&nbsp;Jing Wang ,&nbsp;Yang Xu ,&nbsp;Yixiao Liang ,&nbsp;Li Peng ,&nbsp;Ling Gao ,&nbsp;Jiajun Zhao ,&nbsp;Zhao He","doi":"10.1016/j.lfs.2025.123677","DOIUrl":"10.1016/j.lfs.2025.123677","url":null,"abstract":"<div><h3>Aims</h3><div>Fat preference is mediated by fatty acid receptors in the oral, intestinal, and central nervous systems, but their central nervous system roles remain unclear. Here, we investigated how GPR40, a medium- and long-chain fatty acid receptor, regulates fat preference via agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus (ARC).</div></div><div><h3>Materials and methods</h3><div>AgRP neuron-specific <em>Gpr40</em> knockout mice were generated to investigate the role of GPR40 in dietary fat preference. Behavioral tests were conducted to assess dietary preferences, and metabolic analyses were performed after starvation. We also measured the activity of AgRP neurons and the expression levels of AgRP and neuropeptide Y (NPY) to explore the mechanisms.</div></div><div><h3>Key findings</h3><div>Our results indicate that GPR40 is a novel signaling pathway that regulates fat preference in hypothalamic AgRP neurons, but not in pro-opiomelanocortin (POMC) neurons. AgRP-specific <em>Gpr40</em> knockout mice displayed a reduced preference for fat. This alteration in dietary preference was not associated with behavioral anomalies such as anxiety, depression, or deficits in short-term memory. Additionally, <em>Gpr40</em> deletion in ARC AgRP neurons resulted in a diminished metabolic state, increased AgRP neuronal activity, and elevated levels of AgRP and NPY peptides following starvation, leading to reduced fat intake and increased carbohydrate intake. Inhibition of AgRP neuronal activity in AgRP-specific <em>Gpr40</em> knockout mice rescued the observed changes in fat preference.</div></div><div><h3>Significance</h3><div>GPR40 signaling in AgRP neurons plays a critical role in regulating fat preference by modulating neuronal activity and the expression of AgRP and NPY peptides.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123677"},"PeriodicalIF":5.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-progressive stratification of Becker muscular dystrophy patients: a focus on muscle biopsy fibrosis, inflammation and capillary network","authors":"Simona Zanotti ,&nbsp;Patrizia Ciscato ,&nbsp;Laura Napoli ,&nbsp;Letizia Bertolasi ,&nbsp;Stefania Corti ,&nbsp;Giacomo Pietro Comi ,&nbsp;Maurizio Moggio ,&nbsp;Monica Sciacco ,&nbsp;Michela Ripolone","doi":"10.1016/j.lfs.2025.123676","DOIUrl":"10.1016/j.lfs.2025.123676","url":null,"abstract":"<div><div>Skeletal muscle dystrophies comprise a group of inherited disorders characterized by progressive muscle weakness, with Duchenne and Becker muscular dystrophies (DMD/BMD) being among the most severe. These dystrophies are caused by mutations in the <em>dystrophin</em> gene, resulting in muscle cell instability, chronic inflammation, fibrosis, and impaired muscle regeneration. Although skeletal muscle has intrinsic regenerative potential via satellite cells, the ongoing muscle damage in DMD/BMD depletes these cells and promotes fibrosis. Inflammation also plays a pivotal role, with immune cell infiltration correlating with disease severity.</div><div>This study investigates fibrosis, inflammation, and capillarization in BMD patients across different age groups to clarify how disease progression varies over time. Morphological analyses of muscle biopsies revealed an increase in connective tissue, particularly in adult patients. Pediatric patients showed reduced capillarization, whereas adult patients displayed vascular adaptations, including elevated capillary-to-fibre ratios and capillary contacts, indicative of compensatory mechanisms in response to chronic muscle degeneration.</div><div>Inflammatory profiles also varied with age: younger adult patients exhibited a predominance of CD68-positive macrophages, while older adults demonstrated increased CD4/CD8 T-cell activity.</div><div>Our findings highlight pronounced age-dependent differences in muscle pathology, encompassing structural adaptations, fibrosis, and inflammation, which may be crucial for developing age-tailored therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123676"},"PeriodicalIF":5.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D3, cholecalciferol via its hydroxylmetabolites, receptors and metabolizing enzymes modulates male reproductive functions","authors":"David Tolulope Oluwole ,&nbsp;Ayodeji Folorunsho Ajayi","doi":"10.1016/j.lfs.2025.123680","DOIUrl":"10.1016/j.lfs.2025.123680","url":null,"abstract":"<div><div>Although biologically known for its central role in calcium homeostasis, Vitamin D3 (VD3), owing to its scattered receptors across bodily tissues and the presence of its metabolizing enzymes, has recently garnered scientific attention. This review examined the literature to document the role and specific mechanisms of action of VD3, its receptors, and metabolizing enzymes in male reproduction. Using the keywords Vitamin D3, vitamin D receptors, vitamin D metabolic enzymes, and male reproductive system to search PUBMED and other academic archives, it was observed that VD3, through its interaction with the VDR and with the backing of the activities of its metabolizing enzymes, modulates the male reproductive functions, acting as an antioxidant and anti-inflammatory in reproductive organs to prevent oxidative damages that may result from exposure to environmental toxicants and the increased oxygen utilization by mitochondria owing to high level of unsaturated fatty acids in the testis, thus preventing male infertility.</div></div><div><h3>Essential points</h3><div><ul><li><span>a)</span><span><div>Vitamin D₃, interaction with its receptor and metabolizing enzymes modulates the male reproductive functions</div></span></li><li><span>b)</span><span><div>Damages to reproductive organs result from mitochondrial oxygen utilization, high level of unsaturated fatty acids and environmental toxicants,</div></span></li><li><span>c)</span><span><div>Vitamin D3 modulates spermatogenesis by upregulating enzymes responsible for testicular androgen hormone production</div></span></li><li><span>d)</span><span><div>Vitamin D3 acts as antioxidant and anti-inflammatory agent in reproductive organs to prevent organ damages</div></span></li></ul></div><div><strong>Search Strategy</strong>: PUBMED, GOOGLE SCHOLAR, MEDLINE, SCOPUS database</div><div>This review narrated the impact of VD3 on male reproduction: exploring its Receptor-Mediated and Enzymatic Regulation of Fertility, Erectile Function, Testicular Health, and Sperm Quality. Articles used were obtained from PubMed, MEDLINE, and Scopus databases with the Subject title terms “Vitamin D3” OR “Cholecalciferol” OR “1, 25-Dihydroxyvitamin D3” AND “Male fertility” OR “Erectile function” OR “Testicular health” OR “Sperm quality”, “Vitamin D3” OR “VD3” AND “Vitamin D receptor” OR “VDR” AND “Male reproductive health” OR “Fertility”. “1, 25-Dihydroxyvitamin D3” OR “1-alpha-hydroxylase” AND “Testicular function” OR “Sperm motility” OR “Sperm morphology”. “Vitamin D3” OR “VD3” AND “CYP27B1” OR “CYP24A1” AND “Male reproductive biology” OR “Fertility”. Articles published in English language were used.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123680"},"PeriodicalIF":5.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poldip2 Aggravates inflammation in diabetic retinopathy by impairing mitophagy via the AMPK/ULK1/Pink1 pathway","authors":"Siyu Lin ,&nbsp;Zhiyu Ji ,&nbsp;Jie Gao ,&nbsp;Jiawei Fan ,&nbsp;Jingjing Hou ,&nbsp;Sha Liu ,&nbsp;Chuanxi Wang ,&nbsp;Keyang Chen ,&nbsp;Liming Tao ,&nbsp;Zhengxuan Jiang","doi":"10.1016/j.lfs.2025.123681","DOIUrl":"10.1016/j.lfs.2025.123681","url":null,"abstract":"<div><h3>Background and aim</h3><div>Inflammation is a crucial aspect of the pathophysiology of diabetic retinopathy (DR). Polymerase delta-interacting protein 2 (Poldip2) has been linked to inflammation in various disorders, but its role in DR remains unclear. This study aims to elucidate the underlying mechanisms of Poldip2 in DR.</div></div><div><h3>Methods</h3><div>Transmission Electron Microscopy (TEM) revealed significant mitophagy reduction due to the accumulation of damaged mitochondria in the retinas of Streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rats. In vivo, AAV9-<em>Poldip2</em>-shRNA was administered to STZ-induced DR rats, partially restoring mitophagy. Microglia (BV2) cells cultured in high glucose (HG) conditions exhibited similar behavior. Likewise, BV2 received <em>Poldip2</em>-siRNA treatment to further explore the regulatory mechanism of Poldip2.</div></div><div><h3>Results</h3><div>In vivo, Poldip2 was significantly elevated alongside VEGFR and SQSTM1/P62, while mitophagy markers were inhibited. Under HG conditions, BV2 secret large amounts of pro-inflammatory factors. Human Retinal Microvascular Endothelial Cells (HRMECs) were significantly affected by these HG-cultured BV2, leading to angiogenesis. Notably, Poldip2 knockdown significantly increased Pink1 by preventing its ubiquitination-mediated degradation, thereby enhancing mitophagy and reducing retinal inflammation.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that Poldip2 contributes to DR by promoting Pink1 degradation, which inhibits mitophagy and leads to inflammation. Targeting Poldip2 may offer a novel therapeutic strategy for DR.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123681"},"PeriodicalIF":5.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Indole-3-lactic acid derived from tryptophan metabolism alleviates the sFlt-1-induced preeclampsia-like phenotype via the activation of aryl hydrocarbon receptor” [Life Sci. 361 (2025) 123329]","authors":"Yingying Wei ,&nbsp;Haojun Tian ,&nbsp;Hao Peng ,&nbsp;Ayinisa Wubulikasimu ,&nbsp;Mengtian Wei ,&nbsp;Han Li ,&nbsp;Qizhi He ,&nbsp;Tao Duan ,&nbsp;Yiying Huang ,&nbsp;Kai Wang","doi":"10.1016/j.lfs.2025.123666","DOIUrl":"10.1016/j.lfs.2025.123666","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123666"},"PeriodicalIF":5.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-mediated muscle-hypothalamus crosstalk: Improvement for cognitive dysfunction caused by disrupted circadian rhythm","authors":"Jun-xiao Shi ,&nbsp;Zi-yuan Wang ,&nbsp;Sheng-wen Wang ,&nbsp;Qi Shen ,&nbsp;Xing Tan","doi":"10.1016/j.lfs.2025.123657","DOIUrl":"10.1016/j.lfs.2025.123657","url":null,"abstract":"<div><div>In contemporary societal evolution, the increasing disruption of the natural sleep-wake cycle, attributable to factors such as shift work and overexposure to artificial light, has been paralleled by a marked escalation in the incidence of cognitive impairments and the prevalence of neurodegenerative diseases. Current management strategies for cognitive impairments include pharmacological and non-pharmacological interventions. Pharmacological interventions for cognitive impairments typically involve medications to manage cognitive symptoms and improve neurological functions. However, these drugs show limited long-term efficacy in slowing disease progression and may cause side effects. Given the widespread occurrence of cognitive dysfunction, it is crucial to develop accessible non-pharmacological interventions. Physical activity and exercise have emerged as pivotal lifestyle determinants known to exert a modulatory effect on the risk profile for cognitive dysfunction caused by disrupted circadian rhythms. The skeletal muscle, a dynamic tissue, undergoes a profound morphological and metabolic reconfiguration in response to physical exertion, along with the secretion of myokines. Additionally, the hypothalamus, particularly the ventromedial nuclei, arcuate nuclei, and the suprachiasmatic nucleus, have crucial functions in regulating physical activity, influencing energy metabolism, and managing circadian cycles. Nevertheless, the communication between the hypothalamus and skeletal muscle during exercise is not fully understood. This narrative review integrates current knowledge on the interaction between the hypothalamus and skeletal muscle during exercise, emphasizing its neuroendocrine effects and potential therapeutic implications for alleviating cognitive dysfunction associated with disrupted circadian rhythms.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123657"},"PeriodicalIF":5.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}