Life metabolism最新文献

{"title":"Age-specific effects of hemoglobin A1c, blood pressure, and cholesterol levels on incident cardiovascular diseases among adults with diabetes in China: a 10-year prospective cohort study.","authors":"Yue Yin, Xiaojing Jia, Shengli Wu, Hong Qiao, Guijun Qin, Tiange Wang, Chunyan Hu, Hong Lin, Shuangyuan Wang, Yu Xu, Mian Li, Min Xu, Jie Zheng, Xiadi He, Yingfen Qin, Xulei Tang, Zhen Ye, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Qin Wan, Gang Chen, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Yinfei Zhang, Tianshu Zeng, Chao Liu, Youmin Wang, Tao Yang, Huacong Deng, Lulu Chen, Jiajun Zhao, Yiming Mu, Guang Ning, Yuhong Chen, Jieli Lu, Weiqing Wang, Yufang Bi","doi":"10.1093/lifemeta/loag008","DOIUrl":"10.1093/lifemeta/loag008","url":null,"abstract":"<p><p>Optimal control of hemoglobin A1c (HbA1c), blood pressure, and cholesterol (ABC risk factors) is essential for reducing cardiovascular disease (CVD) risk in individuals with diabetes. However, age-specific contributions of these factors remain inadequately characterized. Using data from the China Cardiometabolic Disease and Cancer Cohort study, we assessed the associations between ABC risk factors and incident CVD among Chinese adults with diabetes, stratified by age groups of < 55, 55 to < 65, 65 to < 75, and ≥ 75 years. Cox proportional hazards models and population-attributable fractions (PAFs) were used to quantify the associations between ABC risk factors and incident CVD. During a median follow-up of 10.1 years, 4707 incident cases of CVD were documented. Higher levels of baseline HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) were significantly associated with increased CVD risk. Age modified these associations (<i>P</i> _interaction < 0.05), with progressively attenuated hazard ratios (HRs) observed in older age groups. Compared with HbA1c < 7.0%, HbA1c ≥ 9.0% showed stronger CVD associations in adults aged < 55 years (HR = 2.42; 95% confidence interval [CI]: 1.98-2.97) than in those aged ≥ 75 years (HR = 1.50; 95% CI: 1.12-2.02), and SBP ≥ 140 mmHg and LDL-C ≥  4.1 mmol/L were significant only in younger groups. The leading contributor to PAFs for CVD was SBP (28.3%), followed by HbA1c (12.0%) and LDL-C (9.2%), with diminishing impacts across older groups. These results underscore the importance of age-specific management of ABC risk factors in diabetes care, with the benefit of stricter risk factor management in younger adults and the need for a more flexible approach in older populations.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag008"},"PeriodicalIF":6.3,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian biology and exercise: the time to move.","authors":"Zhihui Zhang, John A Hawley, Min-Dian Li","doi":"10.1093/lifemeta/loag009","DOIUrl":"10.1093/lifemeta/loag009","url":null,"abstract":"<p><p>Exercise performance in endurance- and power-based events is time-of-day dependent in both humans and rodents. Accordingly, there has been growing interest in determining whether there is an optimal time of day for physical activity that can amplify the well-known benefits of exercise on metabolic health in humans. Here, we discuss critical features of circadian biology that underpin many of the physiological responses to the timing of exercise. Recent studies indicate that the circadian clock regulates exercise capacity through the coordination of tissue-specific physiological responses, including fuel metabolism and mitochondrial biogenesis. Synchronized actions between circadian clocks and clock-output pathways residing in the skeletal muscle and other tissues are likely to explain how external time-of-day cues influence exercise performance and physiological responses to exercise. Understanding the circadian biology of exercise will provide the foundation on which future individualized exercise protocols are prescribed to improve metabolic health outcomes at both individual and population levels.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag009"},"PeriodicalIF":6.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosome: not only for digestion but also for production.","authors":"","doi":"10.1093/lifemeta/loag007","DOIUrl":"10.1093/lifemeta/loag007","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag007"},"PeriodicalIF":6.3,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing the strain on calorie restriction.","authors":"John R Speakman, Sharon E Mitchell","doi":"10.1093/lifemeta/loag006","DOIUrl":"10.1093/lifemeta/loag006","url":null,"abstract":"<p><p>Calorie restriction (CR) is a nutritional intervention known to delay aging and extend lifespan across a wide range of species, raising the possibility of similar benefits in humans. This apparent universality has been questioned by studies reporting shortened lifespan under CR in certain mouse strains. Here, we provide a short perspective on these conflicting findings. Using simple simulation analyses, we explored the apparent strain-specific effects on CR outcomes. Our results illustrate how experimental factors have confounded previous interpretations and led to overemphasis on genotype effects. Reproducible CR studies are crucial for understanding the true potential of CR as a broadly applicable intervention in aging.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag006"},"PeriodicalIF":6.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomes contribute to the synthesis of tricarboxylic acid-related metabolites in the hippocampus.","authors":"Liangliang Kong, Hongying Tan, Xiaoting Zhu, Yiqing Wen, Yang Li","doi":"10.1093/lifemeta/loag005","DOIUrl":"10.1093/lifemeta/loag005","url":null,"abstract":"<p><p>The central nervous system is highly sensitive to energy supply, and the hippocampus operates under sustained metabolic load due to continuous synaptic activity and information processing. Lysosomes couple nutrient status to cellular energetics through the mechanistic target of rapamycin complex 1 (mTORC1) and the autophagy-lysosome pathway, yet their -subcellular contribution to neuronal metabolic profiles remains unclear. To address this, we established an <i>in vivo</i> AAV-LysoTag/Lyso-IP workflow combined with metabolomics to quantify metabolites within mouse hippocampal lysosomes. An <i>in vitro</i> Lyso-IP platform and immunofluorescence provided cell-based validation. Under every-other-day fasting, hippocampal lysosomes exhibited reprogramming: small-molecule substrates derived from amino acids and fatty acids accumulated; bis(monoacylglycero)phosphate was upregulated, indicating enhanced intraluminal vesicle formation and lipid degradation/sorting; -sphingolipids and cardiolipin increased, consistent with selective mitophagy. Notably, high basal lysosomal levels of malic acid and α-ketoglutarate (α-KG) suggested additional sources beyond the mitochondria. Immunofluorescence further showed lysosomal localization of isocitrate dehydrogenase and fumarate hydratase, suggesting partial residency of these enzymes. The oxoglutarate carrier (SLC25A11) signals were observed in LAMP1⁺ compartments, suggesting potential transmembrane exchange of α-KG and malic acid. Together, our data indicate that lysosomal tricarboxylic acid -related metabolites are maintained by three parallel routes: mitochondrial delivery to lysosomes, local production by resident enzymes, and transporter-mediated exchange. These metabolites supplement and reshape neuronal carbon flux and metabolic resilience at the subcellular level. Our findings elevate lysosomes from degradative endpoints to mobilizable metabolic hubs in the brain and provide both methodological and conceptual frameworks for neurometabolic adaptation under energy scarcity.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag005"},"PeriodicalIF":6.3,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A functionally integrated cross-tissue alternative splicing program during short-term calorie restriction.","authors":"Daniel P Phillips, Sharon E Mitchell, Davina Derous, John R Speakman","doi":"10.1093/lifemeta/loaf046","DOIUrl":"10.1093/lifemeta/loaf046","url":null,"abstract":"<p><p>Alternative splicing (AS) involves production of several different RNA molecules from a single pre-mRNA. Calorie restriction (CR) is a sustained calorie deficit without malnutrition, which extends health and lifespan. AS is dysregulated in aging but less so following CR, suggesting a role for AS in the beneficial effects of CR. To test the hypothesis that AS is involved in the CR response and explore its tissue specificity, male C57BL/6 mice were exposed to 3 months of graded CR (0-40% at 10% increments) and RNA sequencing data from six tissues (epididymal white adipose tissue [eWAT], liver, hypothalamus, gastrocnemius muscle, testes, and stomach) were analyzed to provide a multi-tissue characterization of differential AS (DAS). The number of differentially expressed splicing regulators increased with CR levels in all tissues but primarily the muscle, eWAT, and liver. The total number of DAS genes also increased with increasing CR levels and was largely tissue-specific. Most DAS genes were not differentially expressed. DAS was functionally integrated across tissues with the same processes being overrepresented: namely, mitochondria and oxidative phosphorylation, transcription and translation, and quality checking and degradation of RNA and especially proteins. This study demonstrates that short-term CR evokes a functionally integrated cross-tissue AS response in mice that is largely independent of expression changes.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 2","pages":"loaf046"},"PeriodicalIF":6.3,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational progesterone restores menstrual cycle in PCOS patients via enhancing ovary estrogen production.","authors":"Qiwen Yang, Na Kong, Jing Wu, Yan Yang, Xinge Zhang, Yuan Lin, Zhibin Hu, Guijun Yan, Haixiang Sun, Chaojun Li","doi":"10.1093/lifemeta/loag004","DOIUrl":"10.1093/lifemeta/loag004","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, typically characterized by irregular menstrual cycles. Our study found that postpartum menstrual cycles were largely restored in PCOS patients following assisted reproductive technology (ART) therapy. However, this recovery in menstrual cycles was not -associated with any specific ART procedures. Using a PCOS mouse model, we demonstrated that elevated progesterone levels during pregnancy were responsible for normalizing estrous cyclicity. Elevated levels of progesterone induced granulosa cell apoptosis and depleted large follicles, which potentially contributed to ovarian function suppression during pregnancy. Mechanistic studies indicated that progesterone decreased follicle-stimulating hormone receptor (FSHR) expression in a GATA binding protein 2 (GATA2)-dependent manner. Interestingly, the capacity of granulosa cells to convert androgens to estrogens significantly increased after progesterone withdrawal, as evidenced by elevated expression of cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) in granulosa cells when stimulated with follicle-stimulating hormone. In addition, we found that progesterone administration reduced the thickness of the uterine endometrium in PCOS mice. Our findings suggest that sustained high levels of progesterone during pregnancy can enhance ovarian reproductive endocrine capacity and improve endometrial function, thereby facilitating the recovery of postpartum menstrual cycles.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag004"},"PeriodicalIF":6.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timekeepers of the gut: host circadian rhythms and microbial modulators.","authors":"Xianda Ma, Qiyi Yu, Zheng Kuang","doi":"10.1093/lifemeta/loag003","DOIUrl":"10.1093/lifemeta/loag003","url":null,"abstract":"<p><p>The intestine is more than a digestive organ. It is a system under circadian control, where cellular renewal, barrier integrity, absorption, immunity, and microbial ecology are orchestrated in time. Emerging evidence reveals that circadian rhythms not only regulate the daily turnover of intestinal epithelium but also fine-tune digestive enzyme expression, mucosal defense, and gut hormone secretion. These processes are driven by core clock proteins and synchronized by feeding cues, neural signals, and microbial metabolites. The gut microbiota consists of essential symbionts that themselves exhibit diurnal oscillations in composition and function, in turn feeding back to modulate host circadian pathways. Disruption of this host-microbiota temporal alignment, as occurs with jet lag, shift work, or high-fat diets, impairs intestinal homeostasis and elevates risk for inflammation, infection, and metabolic disorders. This review integrates evidence from mouse, zebrafish, fly, and human studies to highlight the rhythmic regulation of gut physiology, emphasizing how coordination between the host clock and microbiota sustains health. Viewing the gut as a circadian conductor underscores new opportunities for chronotherapy and microbiota-targeted interventions.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 2","pages":"loag003"},"PeriodicalIF":6.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytosolic acetyl-CoA: a metabolic regulator of mitophagy.","authors":"Jianhua Xiong","doi":"10.1093/lifemeta/loag002","DOIUrl":"10.1093/lifemeta/loag002","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 2","pages":"loag002"},"PeriodicalIF":6.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative omics analysis incorporating cardiovascular magnetic resonance imaging pinpoints potentially druggable plasma proteins for cardiovascular diseases.","authors":"Weiming Gong, Ping Guo, Lu Liu, Xiubin Sun, Shukang Wang, Fuzhong Xue, Lujia Shen, Zhongshang Yuan","doi":"10.1093/lifemeta/loag001","DOIUrl":"10.1093/lifemeta/loag001","url":null,"abstract":"<p><p>Despite advances in traditional risk factors for cardiovascular diseases (CVDs), significant residual risk of CVDs remains incompletely captured. Integrative analysis incorporating cardiovascular magnetic resonance imaging (CMR) could facilitate to discover novel -therapeutic targets. This study aimed to identify potentially druggable plasma proteins for CVDs by incorporating CMR traits with integrative omics analysis. By integrating protein quantitative trait loci (pQTL) datasets of plasma proteins from Atherosclerosis Risk in Communities (ARIC) study with genome-wide association studies of 19 CVDs and 82 CMR traits, we sequentially used proteome-wide association study (PWAS), Mendelian randomization (MR), and colocalization analysis to identify putatively causal proteins. Replication MR was conducted using deCODE pQTL data, followed by observational association analysis using UK Biobank individual-level data, and multidimensional downstream analyses, as well as phenome-wide MR (Phe-MR). In total, we identified 342 protein-CVD and 115 protein-CMR pairs through PWAS. MR and colocalization ana-lyses revealed 66 protein-CVD and 39 protein-CMR pairs with potential causal relationships, of which 51 protein-CVD and 33 protein-CMR pairs were replicated. Additionally, 26 protein-CVD and 6 protein-CMR pairs showed significantly observational associations. Multidimensional downstream analysis highlighted potential biological pathways and druggability insights. Notably, <i>AGER</i>, <i>CCN3</i>, <i>FER</i>, and <i>SPON1</i> were identified as proteins associated with both CVDs and CMR traits. Phe-MR analysis suggests potential beneficial and adverse effects of these proteins on other diseases. Our findings highlight potentially druggable plasma proteins for CVDs by incorporating CMR traits, providing novel insights into CVD pathogenesis and therapeutic drug development.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"5 3","pages":"loag001"},"PeriodicalIF":6.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}