PMID- 36056774 OWN - NLM STAT- MEDLINE DCOM- 20221021 LR - 20230123 IS - 1474-9726 (Electronic) IS - 1474-9718 (Print) IS - 1474-9718 (Linking) VI - 21 IP - 10 DP - 2022 Oct TI - Importance of Bmal1 in Alzheimer's disease and associated aging-related diseases: Mechanisms and interventions. PG - e13704 LID - 10.1111/acel.13704 [doi] LID - e13704 AB - With the aging world population, the prevalence of aging-related disorders is on the rise. Diseases such as Alzheimer's, type 2 diabetes mellitus (T2DM), Parkinson's, atherosclerosis, hypertension, and osteoarthritis are age-related, and most of these diseases are comorbidities or risk factors for AD; however, our understandings of molecular events that regulate the occurrence of these diseases are still not fully understood. Brain and muscle Arnt-like protein-1 (Bmal1) is an irreplaceable clock gene that governs multiple important physiological processes. Continuous research of Bmal1 in AD and associated aging-related diseases is ongoing, and this review picks relevant studies on a detailed account of its role and mechanisms in these diseases. Oxidative stress and inflammation turned out to be common mechanisms by which Bmal1 deficiency promotes AD and associated aging-related diseases, and other Bmal1-dependent mechanisms remain to be identified. Promising therapeutic strategies involved in the regulation of Bmal1 are provided, including melatonin, natural compounds, metformin, d-Ser2-oxyntomodulin, and other interventions, such as exercise, time-restricted feeding, and adiponectin. The establishment of the signaling pathway network for Bmal1 in aging-related diseases will lead to advances in the comprehension of the molecular and cellular mechanisms, shedding light on novel treatments for aging-related diseases and promoting aging-associated brain health. CI - (c) 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. FAU - Fan, Rongping AU - Fan R AUID- ORCID: 0000-0003-3587-3365 AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Peng, Xuemin AU - Peng X AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Xie, Lei AU - Xie L AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Dong, Kun AU - Dong K AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Ma, Delin AU - Ma D AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Xu, Weijie AU - Xu W AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Shi, Xiaoli AU - Shi X AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Zhang, Shujun AU - Zhang S AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Chen, Juan AU - Chen J AD - Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yu, Xuefeng AU - Yu X AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. FAU - Yang, Yan AU - Yang Y AUID- ORCID: 0000-0001-8146-8040 AD - Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220903 PL - England TA - Aging Cell JT - Aging cell JID - 101130839 RN - 0 (Adiponectin) RN - JL5DK93RCL (Melatonin) RN - 9100L32L2N (Metformin) RN - 0 (ARNTL Transcription Factors) SB - IM MH - Humans MH - Adiponectin MH - Aging/genetics MH - *Alzheimer Disease/genetics/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - *Melatonin MH - *Metformin MH - ARNTL Transcription Factors/metabolism PMC - PMC9577946 OTO - NOTNLM OT - ARNTL transcription factors OT - Alzheimer disease OT - Parkinson disease OT - atherosclerosis OT - diabetes mellitus OT - osteoarthritis OT - type 2 COIS- The authors have no conflicts of interest to disclose. EDAT- 2022/09/04 06:00 MHDA- 2022/10/20 06:00 PMCR- 2022/10/01 CRDT- 2022/09/03 06:32 PHST- 2022/06/16 00:00 [revised] PHST- 2022/02/22 00:00 [received] PHST- 2022/08/11 00:00 [accepted] PHST- 2022/09/04 06:00 [pubmed] PHST- 2022/10/20 06:00 [medline] PHST- 2022/09/03 06:32 [entrez] PHST- 2022/10/01 00:00 [pmc-release] AID - ACEL13704 [pii] AID - 10.1111/acel.13704 [doi] PST - ppublish SO - Aging Cell. 2022 Oct;21(10):e13704. doi: 10.1111/acel.13704. Epub 2022 Sep 3.