Konakchieva Rossitza, Mladenov Mitko, Konaktchieva Marina, Sazdova Iliyana, Gagov Hristo, Nikolaev Georgi
Department of Cell and Developmental Biology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 1164 Sofia, Bulgaria.
Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia.
Int J Mol Sci. 2025 Jun 28;26(13):6267. doi: 10.3390/ijms26136267.
Circadian rhythms govern cellular metabolism, redox balance, and endocrine signaling in numerous tissues. However, chronic disturbance of these biological rhythms, mediated by modern lifestyle factors including shift work, sleep irregularity, and prolonged light exposure, has been increasingly associated with oxidative stress, metabolic dysregulation, and the pathogenesis of chronic diseases. This review discusses recent mechanistic advances that link circadian misalignment with tissue-specific metabolic reprogramming and impaired proteostasis, focusing on metabolic inflammation and associated pathologies. Emerging work reveals a close interdependence between the circadian clock and proteasome-mediated protein turnover and highlights this interplay's importance in maintaining redox homeostasis. Furthermore, circadian modulation of the activity of the inflammasome complex is suggested to represent an important, but largely unexplored, risk factor in the pathobiology of both malignancy and metabolic syndrome. Recently, researchers have proposed them as novel endocrine regulators of systemic energy balance and inflammation, with a focus on their circadian regulation. In addition, the emerging domains of chrono-epigenetics and tissue-specific programming of the clock pathways may serve to usher in novel therapies through precision medicine. Moving ahead, circadian-based therapeutic approaches, including time-restricted feeding, chronopharmacology, and metabolic rewiring, have high potential for re-establishing physiological domain homeostasis linked to metabolic inflammation pathologies. Elucidating this reciprocal relationship between circadian biology and cellular stress pathways may one day facilitate the generation of precise interventions aiming to alleviate the health burden associated with circadian disruption.
昼夜节律调控着众多组织中的细胞代谢、氧化还原平衡和内分泌信号传导。然而，由现代生活方式因素介导的这些生物节律的慢性紊乱，包括轮班工作、睡眠不规律和长时间光照，越来越多地与氧化应激、代谢失调以及慢性疾病的发病机制相关联。本综述讨论了将昼夜节律失调与组织特异性代谢重编程和蛋白质稳态受损联系起来的最新机制进展，重点关注代谢性炎症及相关病理情况。新出现的研究揭示了生物钟与蛋白酶体介导的蛋白质周转之间存在密切的相互依存关系，并强调了这种相互作用在维持氧化还原稳态中的重要性。此外，炎性小体复合物活性的昼夜调节被认为是恶性肿瘤和代谢综合征病理生物学中一个重要但很大程度上未被探索的危险因素。最近，研究人员将它们作为全身能量平衡和炎症的新型内分泌调节因子提出，重点关注它们的昼夜调节。此外，生物钟途径的时程表观遗传学和组织特异性编程等新兴领域可能有助于通过精准医学引入新的治疗方法。展望未来，基于昼夜节律的治疗方法，包括限时进食、时辰药理学和代谢重塑，在重新建立与代谢性炎症病理相关的生理领域稳态方面具有很高的潜力。阐明昼夜生物学与细胞应激途径之间的这种相互关系，也许有一天会促进旨在减轻与昼夜节律紊乱相关的健康负担的精准干预措施的产生。
