Aging Cell最新文献_第5页

DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains. DP1受体阻断可减轻老年大脑外泌体中PTGDS引起的小胶质细胞衰老和认知能力下降。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-19 DOI: 10.1111/acel.70228

Yaru Liu, Pan Liao, Bo Yan, Dai Li, Shishuang Zhang, Wei Zhang, Zexi Jia, Zihan Zhang, Han Gao, Qiang Liu, Fanglian Chen, Ping Lei, Zhenyu Yin

{"title":"DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains.","authors":"Yaru Liu, Pan Liao, Bo Yan, Dai Li, Shishuang Zhang, Wei Zhang, Zexi Jia, Zihan Zhang, Han Gao, Qiang Liu, Fanglian Chen, Ping Lei, Zhenyu Yin","doi":"10.1111/acel.70228","DOIUrl":"https://doi.org/10.1111/acel.70228","url":null,"abstract":"Aging leads to neurodegenerative diseases, such as cognitive decline, which are induced by persistent chronic low-grade inflammation in the brain driven by microglial activation. However, whether and how brain-derived exosomes from aged mice (A-exo) induce a pro-inflammatory state and cellular senescence in microglia within the aging brain is poorly understood. Here, we report that brain-derived exosomes from aged mice (A-exo) cause cognitive decline in normal young mice, inducing microglial overactivation, lipid droplet accumulation, and senescence-associated secretory phenotype (SASP) secretion. This abnormal microglial activity arises from the elevated expression of PTGDS in A-exo due to mouse aging, resulting in increased central and peripheral D-prostanoid receptor 1 (DP1) ligand PGD2 levels, which subsequently leads to sustained DP1 signaling activation. Consequently, this process promotes myeloid cell infiltration, cellular senescence, and cognitive decline by generating a senescent, pro-inflammatory microglial phenotype. Blocking the DP1 receptor ameliorates A-exo-mediated microglial overactivation, myeloid cell infiltration, and cellular senescence. Strikingly, DP1 receptor blockade improves cellular senescence, neuroinflammation, and cognitive decline in aged mice. Our findings reveal a systemic mechanism underlying the sustained activation of microglia following brain aging, paving the way for improving chronic neuroinflammation, cellular senescence, and cognitive decline associated with aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70228"},"PeriodicalIF":7.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex- and APOE Genotype-Dependent Pain Susceptibility and Alzheimer's Risk Mediated by the Lipid Metabolism Enzyme LPCAT2. 脂质代谢酶LPCAT2介导的性别和APOE基因型依赖性疼痛易感性和阿尔茨海默病风险

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-17 DOI: 10.1111/acel.70234

Rai-Hua Lai, Ren-Hua Chung, Wan-Yu Pai, Yi-Chung Chen, Ka-Hei Lam, Cheng-Nong Lai, Jyh-Lyh Juang

{"title":"Sex- and APOE Genotype-Dependent Pain Susceptibility and Alzheimer's Risk Mediated by the Lipid Metabolism Enzyme LPCAT2.","authors":"Rai-Hua Lai, Ren-Hua Chung, Wan-Yu Pai, Yi-Chung Chen, Ka-Hei Lam, Cheng-Nong Lai, Jyh-Lyh Juang","doi":"10.1111/acel.70234","DOIUrl":"https://doi.org/10.1111/acel.70234","url":null,"abstract":"Neuropathological changes that precede or accompany early cognitive decline in Alzheimer's disease (AD) may also impact pain processing; however, the molecular connection between these domains remains unclear. In this study, we investigated whether a shared causal factor underlies both increased pain susceptibility and AD progression. Analysis of two ethnically distinct cohorts revealed a significant association between pain susceptibility and cognitive decline from cognitively normal (CN) status to mild cognitive impairment (MCI), particularly in non-APOE4 (non-E4) males, an unexpected finding given that APOE4 females exhibited the highest overall pain susceptibility across sex and genotype groups. To explore potential drivers of this APOE genotype- and sex-specific association, blood transcriptomic analysis identified LPCAT2 expression as correlating with both heightened pain susceptibility and progression from MCI to AD, most notably in non-E4 males. This relationship was further supported by elevated LPCAT2 protein levels in the hippocampus of postmortem non-E4 male AD patients. Strengthening this link, our genetic association analysis across four cohorts identified several functional LPCAT2 variants that not only influenced its expression but were also associated with altered pain susceptibility, increased AD risk, and accelerated progression from MCI to AD. To move beyond correlation and assess causality, Mendelian randomization analysis supported a causal role for LPCAT2 in both pain susceptibility and MCI-to-AD progression. Collectively, these findings identify LPCAT2 as a key molecular link between altered pain processing and AD progression, highlighting its potential as both a therapeutic target for genotype- and sex-specific subpopulations and a prognostic biomarker for MCI-to-AD conversion.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70234"},"PeriodicalIF":7.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease. α -酮戊二酸改善APP/PS1小鼠阿尔茨海默病模型的突触可塑性缺陷

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-17 DOI: 10.1111/acel.70235

Sheeja Navakkode, Brian K Kennedy

{"title":"Alpha-Ketoglutarate Ameliorates Synaptic Plasticity Deficits in APP/PS1 Mice Model of Alzheimer's Disease.","authors":"Sheeja Navakkode, Brian K Kennedy","doi":"10.1111/acel.70235","DOIUrl":"https://doi.org/10.1111/acel.70235","url":null,"abstract":"Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders, characterized by a progressive decline in cognitive function. Increasing evidence indicates that alpha-ketoglutarate (AKG), a key metabolite in the tricarboxylic acid (TCA) cycle, can extend lifespan and healthspan across various animal models, raising interest in its potential neuroprotective effects in age-related disorders such as AD. Our previous research found that dietary supplementation with calcium alpha-ketoglutarate (CaAKG), a calcium derivative of AKG, enhances both lifespan and healthspan in mice. However, little is known about the neuroprotective role of AKG/CaAKG in AD. Here, we show that CaAKG could rescue synaptic deficits that are associated with AD. Treatment with AKG or CaAKG ameliorates long-term potentiation (LTP) at hippocampal CA1 synapses in APP/PS1 mice, with a more profound effect in female AD mice than in males. The effects of CaAKG were mediated through an NMDA receptor-independent mechanism involving L-type calcium channels (LTCC) and calcium-permeable AMPA receptors (CP-AMPARs). Analysis of protein expression showed that AD hippocampal slices treated with CaAKG exhibited increased LC3-II levels, indicating enhanced autophagy. Similarly, rapamycin, an mTOR inhibitor, also rescued LTP deficits in AD mice, suggesting that the observed increase in autophagy may contribute to neuroprotection. Interestingly, rapamycin showed differential effects, as it rescued LTP in AD mice but blocked LTP in WT mice. We also observed that CaAKG facilitated synaptic tagging and capture (STC), a widely studied cellular model for associative memory, indicating its potential to facilitate associative memory. Overall, our findings suggest that CaAKG has neuroprotective effects in APP/PS1 mice. We propose CaAKG as a promising therapeutic target not only for aging but also for AD and potentially other age-associated neurodegenerative diseases, highlighting geroprotective strategies as viable alternatives for the prevention and treatment of AD.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70235"},"PeriodicalIF":7.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regenerate to "Rejuvenate": Insights From Adult Resident Stem Cells of Aged Flatworms and Mice. 再生到“年轻化”：来自成年扁平虫和小鼠的成年常驻干细胞的见解。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-14 DOI: 10.1111/acel.70236

Kevin A Murach, Cory M Dungan, Toby L Chambers, Steve Horvath, Jayakrishnan Nandakumar, Vadim N Gladyshev, Scott D Pletcher, Xiaoting Dai, Longhua Guo

引用次数: 0

Association of Eating Window With Mortality Among US Adults: Insights From a Nationally Representative Study. 美国成年人饮食窗口与死亡率的关系：来自一项全国代表性研究的见解。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-13 DOI: 10.1111/acel.70230

Ziling Mao, Haley Grant, Stephen B Kritchevsky, Anne B Newman, Samaneh Farsijani

{"title":"Association of Eating Window With Mortality Among US Adults: Insights From a Nationally Representative Study.","authors":"Ziling Mao, Haley Grant, Stephen B Kritchevsky, Anne B Newman, Samaneh Farsijani","doi":"10.1111/acel.70230","DOIUrl":"https://doi.org/10.1111/acel.70230","url":null,"abstract":"Time-based diets have gained popularity for their health benefits, but their effects on human longevity remain unclear, with most evidence from short-term human trials and animal studies. We determined the associations between eating window and mortality among U.S. adults. We conducted a prospective cohort study using NHANES 2003-2018 data linked to mortality records through December 2019. The analytic sample included 33,052 adults (aged 20 and above) with two complete 24-h dietary recalls collected at baseline. Eating window was defined as the time between first and last consumption of any food/beverage containing > 0 kcal within 24 h. We used survey-weighted Cox regression with Restricted Cubic Splines (RCS) to model nonlinear associations, treating eating window as both a continuous and categorical variable (< 8.0-≥ 15.0 h/day). Models were adjusted for sociodemographic, lifestyle, health, and dietary factors. Subgroup analyses were conducted by age, sex, and race/ethnicity. Over a median follow-up of 8 years, there were 4158 all-cause, 1277 cardiovascular, and 989 cancer deaths. RCS models showed a U-shaped association between eating window and mortality, with the lowest risk at ~11-12 h/day (p = 0.004). Shorter windows (≤ 8 h) were linked to ≥ 30% higher all-cause mortality, especially in older adults, and > 50% higher cardiovascular mortality in older adults, men, and Whites. Longer eating window categories (≥ 15 h/day) were associated with 25% higher all-cause mortality (95% CI: 1.01-1.55). Moderate eating windows (~11-12 h/day) are linked to the lowest mortality risk, with deviations associated with higher risk. Differences across demographic groups highlight the need for personalized guidance.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70230"},"PeriodicalIF":7.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Entropy, Assessed by Homeostatic Dysregulation on Electrocardiograms Predicts Fracture and Mortality. 通过心电图的稳态失调评估的熵可以预测骨折和死亡率。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-10 DOI: 10.1111/acel.70227

Namki Hong, Sang Wouk Cho, Jungheui Kim, Hanjin Park, Dong-Seon Kang, Seng Chan You, Hee Tae Yu, Kyoung Min Kim, Yumie Rhee, Alan A Cohen, Steven R Cummings

{"title":"Entropy, Assessed by Homeostatic Dysregulation on Electrocardiograms Predicts Fracture and Mortality.","authors":"Namki Hong, Sang Wouk Cho, Jungheui Kim, Hanjin Park, Dong-Seon Kang, Seng Chan You, Hee Tae Yu, Kyoung Min Kim, Yumie Rhee, Alan A Cohen, Steven R Cummings","doi":"10.1111/acel.70227","DOIUrl":"https://doi.org/10.1111/acel.70227","url":null,"abstract":"Entropy, characterized by increased disorder throughout biological systems, can be quantified by homeostatic dysregulation (HD). One potential measure of HD is the dispersion of points from a normal value, approximated at the individual level by Mahalanobis distance (DM). We hypothesized that greater HD in electrocardiogram (ECG) would also reflect greater HD in the musculoskeletal system which, in turn, would be associated with age and manifest as an increased risk of fracture independently of age, bone mineral density (BMD), and history of fracture. We further hypothesized that greater ECG-HD would be associated with increased risk of all-cause mortality. A cohort of 7738 individuals aged 40 years or older who underwent a screening 12-lead ECG between 2007 and 2018 was analyzed (mean age 63.5 years; 59.5% women; 5.5 years follow-up). ECG-HD was calculated as the natural log-transformed DM of five ECG measurements (ventricular rate, QRS duration, corrected QT interval, R axis, and T axis) referenced to young individuals (age 19-29). ECG-HD increased with age (r = 0.28). Each standard deviation increment in ECG-HD was associated with a 48% higher unadjusted fracture risk (HR 1.48, 95% CI 1.37-1.58) and remained significant after adjustment for clinical risk factors, ECG diagnoses, and femoral neck BMD (aHR 1.28, 95% CI 1.15-1.42). ECG-HD was also associated with vertebral, nonvertebral, and hip fractures, and with mortality (aHR 1.44, 95% CI 1.18-1.74). ECG-HD, a measurement of entropy in the cardiac system, was associated with fracture risk and mortality in adults, independent of clinical risk factors, BMD, and ECG diagnoses.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70227"},"PeriodicalIF":7.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STN1 Shields CTC1 From TRIM32-Mediated Ubiquitination to Prevent Cellular Aging. STN1屏蔽trim32介导的CTC1泛素化以防止细胞衰老

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-09 DOI: 10.1111/acel.70214

Yina Lan, Xiaole Liang, Guotao Kuang, Tengfei Ma, Fangyingnan Zhang, Zaoli Huang, Huan Wang, Zhenhua Luo, Xuyang Feng

{"title":"STN1 Shields CTC1 From TRIM32-Mediated Ubiquitination to Prevent Cellular Aging.","authors":"Yina Lan, Xiaole Liang, Guotao Kuang, Tengfei Ma, Fangyingnan Zhang, Zaoli Huang, Huan Wang, Zhenhua Luo, Xuyang Feng","doi":"10.1111/acel.70214","DOIUrl":"https://doi.org/10.1111/acel.70214","url":null,"abstract":"The CST (CTC1-STN1-TEN1) complex, a single-stranded DNA (ssDNA) binding complex, is essential for telomere maintenance and genome stability. Depletion of either CTC1 or STN1 results in cellular senescence, while mutations in these components are associated with severe hereditary disorders. In this study, we demonstrate that the direct STN1-CTC1 interaction stabilizes CTC1 by preventing its degradation via TRIM32 mediated ubiquitination. Functional assays indicate that TRIM32 and the CTC1/STN1 complex exert opposing effects on cellular proliferation. Additionally, transcriptomic analysis of large-scale RNA sequencing data from the Genotype-Tissue Expression (GTEx) reveals inverse expression patterns of TRIM32 and CTC1/STN1 during somatic cell aging. Structural modeling using AlphaFold3 predicts that the TRIM32-CTC1 interaction occurs at the OB-G domain of CTC1, with the binding interface positioned near the STN1-interacting region, termed the \"cleft\" motif. Mechanistically, STN1 likely associates with the OB-G domain of CTC1, competing with TRIM32 for binding sites and thereby interfering with TRIM32-mediated ubiquitination of CTC1. Collectively, our findings identify STN1 as a critical regulator of CST complex integrity and cellular aging by safeguarding CTC1 from TRIM32-driven ubiquitin-proteasome degradation.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70214"},"PeriodicalIF":7.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of Hippo Signaling Through Ablation of Lats1 and Lats2 Protects Against Cognitive Decline in 5xFAD Mice via Increasing Neuronal Resilience Against Ferroptosis. 通过消融Lats1和Lats2抑制Hippo信号通过增加神经元对铁下垂的恢复力来保护5xFAD小鼠的认知能力下降。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-09 DOI: 10.1111/acel.70218

Robert C Evans, Nawab John Dar, Liuji Chen, Ren Na, Jason C O'Connor, Jing Jiang, Siyuan Zheng, Qitao Ran

{"title":"Inhibition of Hippo Signaling Through Ablation of Lats1 and Lats2 Protects Against Cognitive Decline in 5xFAD Mice via Increasing Neuronal Resilience Against Ferroptosis.","authors":"Robert C Evans, Nawab John Dar, Liuji Chen, Ren Na, Jason C O'Connor, Jing Jiang, Siyuan Zheng, Qitao Ran","doi":"10.1111/acel.70218","DOIUrl":"https://doi.org/10.1111/acel.70218","url":null,"abstract":"The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice. To determine how inhibition of Hippo signaling might affect disease pathogenesis, we generated 5xFAD mice with conditional neuronal ablation of Lats1 and Lats2, the gatekeepers of Hippo signaling activity. Our results indicated that 5xFAD mice with ablation of Lats1 and Lats2 were protected against cognitive decline compared with control 5xFAD mice, and this protection was correlated with a marked reduction in neurodegeneration. Interestingly, primary culture neurons with ablation of Lats1 and Lats2 had significantly increased survival following treatment with chemical inducers of ferroptosis and exhibited reduced lipid peroxidation, the driving force of ferroptotic cell death. Moreover, 5xFAD mice with ablation of Lats1 and Lats2 showed reduced lipid peroxidation, and transcriptomic analysis revealed that 5xFAD mice with ablation of Lats1 and Lats2 had enriched metabolic pathways associated with ferroptosis. These results indicate that inhibition of Hippo signaling activity confers neural protection in 5xFAD mice by augmenting resilience against ferroptosis.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70218"},"PeriodicalIF":7.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging. mTOR-Tfeb-Fabp7a轴通过减缓心脏衰老改善bag3型心肌病

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-08 DOI: 10.1111/acel.70216

Yonghe Ding, Xueling Ma, Feixiang Yan, Baul Yoon, Wei Wei, Yuji Zhang, Xueying Lin, Xiaolei Xu

{"title":"An mTOR-Tfeb-Fabp7a Axis Ameliorates bag3 Cardiomyopathy via Decelerating Cardiac Aging.","authors":"Yonghe Ding, Xueling Ma, Feixiang Yan, Baul Yoon, Wei Wei, Yuji Zhang, Xueying Lin, Xiaolei Xu","doi":"10.1111/acel.70216","DOIUrl":"https://doi.org/10.1111/acel.70216","url":null,"abstract":"While BAG3 has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in BAG3-related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish bag3 cardiomyopathy model. Given the known cardioprotective effects of mtor inhibition and the fact that transcription factor EB (tfeb) encodes a direct downstream phosphorylation target of mTOR signaling, we generated a cardiomyocyte-specific transgenic line overexpressing tfeb (Tg[cmlc2:tfeb]). This overexpression was sufficient to restore defective proteostasis and rescue cardiac dysfunction in the bag3 cardiomyopathy model. Importantly, we detected accelerated cardiac senescence in the bag3 cardiomyopathy model, which can be mitigated by Tg(cmlc2:tfeb). We compared cardiac transcriptomes between the Tg(cmlc2:tfeb) transgenic fish and the mtorxu015/+ mutant and found that inhibition of the fatty acid binding protein a (fabp7a) gene exerts therapeutic effects. Consistent with this genetic evidence, we detected elevated fabp7a expression in the bag3 cardiomyopathy model, whereas cardiomyocyte-specific overexpression of fabp7a induced dysregulated proteostasis, accelerated cardiac senescence, and cardiac dysfunction. To elucidate the functions of Fabp7a in normative cardiac aging, we turned to the African Turquoise Killifish. We noted elevated Fabp7a expression in the hearts of aged killifish, and pharmacological inhibition of Fabp7a mitigated the cardiac aging process. Together, this study uncovered accelerated cardiac senescence as a key pathological event in bag3 cardiomyopathy and reveals that manipulating the mTOR-Tfeb-Fabp7a axis can mitigate this pathology and confer cardioprotective effects.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70216"},"PeriodicalIF":7.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic Age Acceleration and Cardiometabolic Biomarkers in Response to Weight-Loss Dietary Interventions Among Obese Individuals: The MACRO Trial. 表观遗传年龄加速和心脏代谢生物标志物对肥胖个体减肥饮食干预的反应：MACRO试验。

IF 7.1 1区医学

Aging Cell Pub Date : 2025-09-08 DOI: 10.1111/acel.70224

Minghao Kou, Xiang Li, Yoriko Heianza, Kirsten Dorans, Lydia Bazzano, Lu Qi

{"title":"Epigenetic Age Acceleration and Cardiometabolic Biomarkers in Response to Weight-Loss Dietary Interventions Among Obese Individuals: The MACRO Trial.","authors":"Minghao Kou, Xiang Li, Yoriko Heianza, Kirsten Dorans, Lydia Bazzano, Lu Qi","doi":"10.1111/acel.70224","DOIUrl":"https://doi.org/10.1111/acel.70224","url":null,"abstract":"Epigenetic clocks have emerged as promising biomarkers of aging, but their responsiveness to lifestyle interventions and relevance for short-term changes in cardiometabolic health remain uncertain. In this study, we examined the associations between three epigenetic aging measures (DunedinPACE, PCPhenoAge acceleration, and PCGrimAge acceleration) and a broad panel of cardiometabolic biomarkers in 144 obese participants from the MACRO trial, a 12-month weight-loss dietary intervention comparing low-carbohydrate and low-fat diets. At pre-intervention baseline, DunedinPACE was significantly associated with several cardiometabolic biomarkers (FDR [false discovery rate] < 0.05), including insulin, homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, adiponectin, and ghrelin. These associations were substantially attenuated following the intervention, with only CRP and adiponectin remaining significant. Changes in epigenetic aging measures were not significantly associated with changes in biomarkers, nor did they mediate the effects of weight loss. Our findings highlight DunedinPACE as a sensitive biomarker of cardiometabolic health in adults with obesity but raise questions about the utility of epigenetic clocks as causal targets in short-term lifestyle interventions. While caloric restriction may attenuate some phenotypic manifestations of biological aging, short-term changes in epigenetic aging measures may not fully reflect underlying cardiometabolic changes. These results underscore the need for caution in interpreting epigenetic aging as a modifiable intervention target.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e70224"},"PeriodicalIF":7.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0