Masayoshi Suda, Tamar Tchkonia, James L Kirkland, Tohru Minamino
{"title":"Targeting senescent cells for the treatment of age-associated diseases.","authors":"Masayoshi Suda, Tamar Tchkonia, James L Kirkland, Tohru Minamino","doi":"10.1093/jb/mvae091","DOIUrl":"10.1093/jb/mvae091","url":null,"abstract":"<p><p>Cellular senescence, which entails cellular dysfunction and inflammatory factor release-the senescence-associated secretory phenotype (SASP)-is a key contributor to multiple disorders, diseases and the geriatric syndromes. Targeting senescent cells using senolytics has emerged as a promising therapeutic strategy for these conditions. Among senolytics, the combination of dasatinib and quercetin (D + Q) was the earliest and one of the most successful so far. D + Q delays, prevents, alleviates or treats multiple senescence-associated diseases and disorders with improvements in healthspan across various pre-clinical models. While early senolytic therapies have demonstrated promise, ongoing research is crucial to refine them and address such challenges as off-target effects. Recent advances in senolytics include new drugs and therapies that target senescent cells more effectively. The identification of senescence-associated antigens-cell surface molecules on senescent cells-pointed to another promising means for developing novel therapies and identifying biomarkers of senescent cell abundance.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"177-187"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on 'Structural insights into a bacterial β-glucosidase capable of degrading sesaminol triglucoside to produce sesaminol: towards the understanding of the aglycone recognition mechanism by the C-terminal lid domain'.","authors":"Masamichi Nagae","doi":"10.1093/jb/mvae094","DOIUrl":"10.1093/jb/mvae094","url":null,"abstract":"<p><p>Sesaminol is an organic compound that shows the strong antioxidant, anti-inflammatory and neuroprotective properties. Sesaminol triglucoside (STG) is a glycosylated form of sesaminol and abundantly exists in sesame seeds. However, typical β-glucosidases could not deglycosylate STG probably due to its bulky aglycone. PSTG1 and 2 are β-glucosidases lately isolated from Paenibacillis sp. KB0459 and have the capacity to deglycosylate STG. A recent report by Yanai et al. (J. Biochem. 2023; 174:335-344) revealed the unique domain architecture of PSTG1. Apart from other β-glucosdasies in the GH3 family, PSTG1 has a novel accessary domain (domain 4) at the C-terminus. Domain 4 contributes to the dimer formation and is located close to the active site. Interestingly, several hydrophobic residues are exposed, suggesting that this domain may recognize the hydrophobic aglycone of STG. The physiological functions of the non-catalytic domains in glyco-enzymes are sometimes overlooked. This paper sheds light on the aglycone recognition by novel accessary domain.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"199-202"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional diversity of senescent cells in driving ageing phenotypes and facilitating tissue regeneration.","authors":"Yasuhiro Nakano, Yoshikazu Johmura","doi":"10.1093/jb/mvae098","DOIUrl":"10.1093/jb/mvae098","url":null,"abstract":"<p><p>As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the ageing process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development and repair. This review provides a comprehensive examination of the dual nature of senescent cells, evaluating their deleterious contributions to chronic inflammation, tissue dysfunction and disease, as well as their beneficial roles in maintaining physiological homeostasis. Additionally, we explored the therapeutic potential of senolytic agents designed to selectively eliminate detrimental senescent cells while considering the delicate balance between transient and beneficial senescence and the persistence of pathological senescence. A deeper understanding of these dynamics is critical to develop novel interventions aimed at mitigating age-related dysfunctions and enhancing healthy life expectancies.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"189-195"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sachie Chikamatsu, Yasufumi Sakakibara, Kimi Takei, Risa Nishijima, Koichi M Iijima, Michiko Sekiya
{"title":"Supplementation of essential amino acids suppresses age-associated sleep loss and sleep fragmentation but not loss of rhythm strength under yeast-restricted malnutrition in Drosophila.","authors":"Sachie Chikamatsu, Yasufumi Sakakibara, Kimi Takei, Risa Nishijima, Koichi M Iijima, Michiko Sekiya","doi":"10.1093/jb/mvae090","DOIUrl":"10.1093/jb/mvae090","url":null,"abstract":"<p><p>Sleep quality and quantity decrease with age, and sleep disturbance increases the risk of many age-associated diseases. There is a significant relationship between nutritional status and sleep outcomes, with malnutrition inducing poor sleep quality in older adults. However, it remains elusive whether, and if so how, nutritional supplementation prevents age-associated sleep problems. Here, we utilized Drosophila to investigate the effects of a malnutrition diet with restricted yeast, a primary protein source, and supplementation of 10 essential amino acids (EAAs) on sleep profiles during ageing. Compared with the standard diet containing 2.7% yeast, the malnutrition diet containing 0.27% yeast significantly decreased target of rapamycin (TOR) signalling and shortened the lifespan of male Canton-S flies. By contrast, age-associated sleep loss, sleep fragmentation and loss of rhythm strength were similarly observed under both diets. Supplementation of the malnutrition diet with EAAs in restricted yeast significantly ameliorated age-associated sleep loss and sleep fragmentation without altering loss of rhythm strength. It also rescued decreased TOR signalling activity but not the shortened lifespan, suggesting that the effects of EAAs on sleep integrity are independent of TOR activity and lifespan regulation. These results may help to develop dietary interventions that improve age-related sleep problems in humans.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"225-237"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Etomoxir suppresses the expression of PPARγ2 and inhibits the thermogenic gene induction of brown adipocytes through pathways other than β-oxidation inhibition.","authors":"Hiroki Shimura, Sota Yamamoto, Isshin Shiiba, Mami Oikawa, Shohei Uchinomiya, Akio Ojida, Shigeru Yanagi, Hisae Kadowaki, Hideki Nishitoh, Toshifumi Fukuda, Shun Nagashima, Tomoyuki Yamaguchi","doi":"10.1093/jb/mvae092","DOIUrl":"10.1093/jb/mvae092","url":null,"abstract":"<p><p>Brown adipocytes are characterized by a high abundance of mitochondria, allowing them to consume fatty acids for heat production. Increasing the number of brown adipocytes is considered a promising strategy for combating obesity. However, the molecular mechanisms underlying their differentiation remain poorly understood. In this study, we demonstrate that etomoxir, an inhibitor of Carnitine Palmitoyltransferase 1 (CPT1), inhibits their differentiation through mechanisms independent of β-oxidation inhibition. In the presence of etomoxir during brown adipocyte differentiation, reduced expression of the thermogenic gene UCP1 and decreased lipid droplets formation were observed. Furthermore, a transient reduction in the expression of PPARγ2, a critical factor in adipocyte differentiation, was also observed in the presence of etomoxir. These findings suggest the presence of a regulatory mechanism that specifically enhances PPARγ2 expression during brown adipocyte differentiation, thereby modulating thermogenic gene expression.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"203-212"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular senescence: mechanisms and relevance to cancer and aging.","authors":"Shota Yamauchi, Akiko Takahashi","doi":"10.1093/jb/mvae079","DOIUrl":"10.1093/jb/mvae079","url":null,"abstract":"<p><p>Cellular senescence is an irreversible cell cycle arrest induced by stresses such as telomere shortening and oncogene activation. It acts as a tumor suppressor mechanism that prevents the proliferation of potentially tumorigenic cells. Paradoxically, senescent stromal cells that arise in the tumor microenvironment have been shown to promote tumor progression. In addition, senescent cells that accumulate in vivo over time are thought to contribute to aging and age-related diseases. These deleterious effects of senescent cells involve the secretion of bioactive molecules such as inflammatory cytokines and chemokines, a phenomenon known as the senescence-associated secretory phenotype. While the role of cellular senescence in vivo is becoming increasingly clear, the intracellular signaling pathways that induce the expression of senescent phenotypes are not fully understood. In this review, we outline senescence-associated signaling pathways and their relevance to cancer and aging.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"163-169"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular senescence in the cancer microenvironment.","authors":"Satoru Meguro, Makoto Nakanishi","doi":"10.1093/jb/mvaf001","DOIUrl":"10.1093/jb/mvaf001","url":null,"abstract":"<p><p>In this ageing society, the number of patients suffering from age-related diseases, including cancer, is increasing. Cellular senescence is a cell fate that involves permanent cell cycle arrest. Accumulated senescent cells in tissues over time present senescence-associated secretory phenotype (SASP) and make the inflammatory context, disturbing the tumour microenvironment. In particular, the effect of senescent cancer-associated fibroblasts on cancer progression has recently come under the spotlight. Although scientific evidence on the impact of cellular senescence on cancer is emerging, the association between cellular senescence and cancer is heterogeneous and the comprehensive mechanism is still not revealed. Recently, a therapy targeting senescent cells, senotherapeutics, has been reported to be effective against cancer in preclinical research and even clinical trials. With further research, the development of senotherapeutics as a novel cancer therapy is expected.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"171-176"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on: γ-enolase (ENO2) is methylated at the Nτ position of His-190 among enolase isozymes.","authors":"Mitsuharu Hattori","doi":"10.1093/jb/mvae088","DOIUrl":"10.1093/jb/mvae088","url":null,"abstract":"","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"197-198"},"PeriodicalIF":2.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of UGT8 as a monogalactosyl diacylglycerol synthase in mammals.","authors":"Yohsuke Ohba, Mizuki Motohashi, Makoto Arita","doi":"10.1093/jb/mvae084","DOIUrl":"10.1093/jb/mvae084","url":null,"abstract":"<p><p>Monogalactosyl diacylglycerol (MGDG) is a major membrane lipid component in plants and is crucial for proper thylakoid functioning. However, MGDG in mammals has not received much attention, partly because of its relative scarcity in mammalian tissues. In addition, the biosynthetic pathway of MGDG in mammals has not been thoroughly analysed, although some reports have suggested that UGT8, a ceramide galactosyltransferase, has the potential to catalyse MGDG biosynthesis. Here, we successfully captured the endogenous levels of MGDG in HeLa cells using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)-based lipidomics. Cellular MGDG was completely depleted in CRISPR/Cas9-mediated UGT8 knockout (KO) HeLa cells. Transient overexpression of UGT8 enhanced MGDG production in HeLa cells, and the corresponding cell lysates displayed MGDG biosynthetic activity in vitro. Site-directed mutagenesis revealed that His358 within the UGT signature sequence was important for its activity. UGT8 was localized in the endoplasmic reticulum and activation of the unfolded protein response by membrane lipid saturation was impaired in UGT8 KO cells. These results demonstrate that UGT8 is an MGDG synthase in mammals and that UGT8 regulates membrane lipid saturation signals in cells.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"141-152"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter W T Lee, Minoru Kobayashi, Takakuni Dohkai, Itsuki Takahashi, Takumi Yoshida, Hiroshi Harada
{"title":"2-Oxoglutarate-dependent dioxygenases as oxygen sensors: their importance in health and disease.","authors":"Peter W T Lee, Minoru Kobayashi, Takakuni Dohkai, Itsuki Takahashi, Takumi Yoshida, Hiroshi Harada","doi":"10.1093/jb/mvae087","DOIUrl":"10.1093/jb/mvae087","url":null,"abstract":"<p><p>Since low oxygen conditions below physiological levels, hypoxia, are associated with various diseases, it is crucial to understand the molecular basis behind cellular response to hypoxia. Hypoxia-inducible factors (HIFs) have been revealed to primarily orchestrate the hypoxic response at the transcription level and have continuously attracted great attention over the past three decades. In addition to these hypoxia-responsive effector proteins, 2-oxoglutarate-dependent dioxygenase (2-OGDD) superfamily including prolyl-4-hydroxylase domain-containing proteins (PHDs) and factor inhibiting HIF-1 (FIH-1) has attracted even greater attention in recent years as factors that act as direct oxygen sensors due to their necessity of oxygen for the regulation of the expression and activity of the regulatory subunit of HIFs. Herein, we present a detailed classification of 2-OGDD superfamily proteins, such as Jumonji C-domain-containing histone demethylases, ten-eleven translocation enzymes, AlkB family of DNA/RNA demethylases and lysyl hydroxylases, and discuss their specific functions and associations with various diseases. By introducing the multifaceted roles of 2-OGDD superfamily proteins in the hypoxic response, this review aims to summarize the accumulated knowledge about the complex mechanisms governing cellular adaptation to hypoxia in various physiological and pathophysiological contexts.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"79-104"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}