Aging Cell最新文献_第8页

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny. 增加线粒体突变异质性诱导多能干细胞及其分化后代的衰老表型。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-16 DOI: 10.1111/acel.14402

Amy R Vandiver, Alejandro Torres, Amberly Sanden, Thang L Nguyen, Jasmine Gasilla, Mary T Doan, Vahan Martirosian, Austin Hoang, Jonathan Wanagat, Michael A Teitell

{"title":"Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny.","authors":"Amy R Vandiver, Alejandro Torres, Amberly Sanden, Thang L Nguyen, Jasmine Gasilla, Mary T Doan, Vahan Martirosian, Austin Hoang, Jonathan Wanagat, Michael A Teitell","doi":"10.1111/acel.14402","DOIUrl":"https://doi.org/10.1111/acel.14402","url":null,"abstract":"The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy. We reprogrammed three human fibroblast lines with known heteroplasmy for deleterious mtDNA point or deletion mutations. Quantification of mutation heteroplasmy in the resulting 76 induced pluripotent stem cell (iPSC) clones yielded a bimodal distribution, creating three sets of clones with high levels or absent mutation heteroplasmy with matched nuclear genomes. iPSC clones with elevated deletion mutation heteroplasmy show altered growth dynamics, which persist in iPSC-derived progenitor cells. We identify transcriptomic and metabolic shifts consistent with increased investment in neutral lipid synthesis as well as increased epigenetic age in high mtDNA deletion mutation iPSC, consistent with changes occurring in cellular aging. Together, these data demonstrate that high mtDNA mutation heteroplasmy induces changes occurring in cellular aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14402"},"PeriodicalIF":8.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833193","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

Age-associated accumulation of RAB9 disrupts oocyte meiosis. 年龄相关的RAB9积累破坏卵母细胞减数分裂。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-15 DOI: 10.1111/acel.14449

Min Gao, Fang Wang, Tengteng Xu, Yanling Qiu, Tianqi Cao, Simiao Liu, Wenlian Wu, Yitong Zhou, Haiying Liu, Fenghua Liu, Junjiu Huang

{"title":"Age-associated accumulation of RAB9 disrupts oocyte meiosis.","authors":"Min Gao, Fang Wang, Tengteng Xu, Yanling Qiu, Tianqi Cao, Simiao Liu, Wenlian Wu, Yitong Zhou, Haiying Liu, Fenghua Liu, Junjiu Huang","doi":"10.1111/acel.14449","DOIUrl":"https://doi.org/10.1111/acel.14449","url":null,"abstract":"The critical role of some RAB family members in oocyte meiosis has been extensively studied, but their role in oocyte aging remains poorly understood. Here, we report that the vesicle trafficking regulator, RAB9 GTPase, is essential for oocyte meiosis and aging in humans and mice. RAB9 was mainly located at the meiotic spindle periphery and cortex during oocyte meiosis. In humans and mice, we found that the RAB9 protein level were significantly increased in old oocytes. Age-related accumulation of RAB9 inhibits first polar body extrusion and reduces the developmental potential of oocytes. Further studies showed that increased Rab9 disrupts spindle formation and chromosome alignment. In addition, Rab9 overexpression disrupts the actin cap formation and reduces the cortical actin levels. Mechanically, Rab9-OE increases ROS levels, decreases mitochondrial membrane potential, ATP content and the mtDNA/nDNA ratio. Further studies showed that Rab9-OE activates the PINK1-PARKIN mitophagy pathway. Importantly, we found that reducing RAB9 protein expression in old oocytes could partially improve the rate of old oocyte maturation, ameliorate the accumulation of age-related ROS levels and spindle abnormalities, and partially rescue ATP levels, mtDNA/nDNA ratio, and PINK1 and PARKIN expression. In conclusion, our results suggest that RAB9 is required to maintain the balance between mitochondrial function and meiosis, and that reducing RAB9 expression is a potential strategy to ameliorate age-related deterioration of oocyte quality.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14449"},"PeriodicalIF":8.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826799","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

Association of metabolomic aging acceleration and body mass index phenotypes with mortality and obesity-related morbidities. 代谢组学老化加速和体重指数表型与死亡率和肥胖相关发病率的关联。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-12 DOI: 10.1111/acel.14435

Xiaomin Zeng, Ruiye Chen, Danli Shi, Xiayin Zhang, Ting Su, Yaxin Wang, Yijun Hu, Mingguang He, Honghua Yu, Xianwen Shang

{"title":"Association of metabolomic aging acceleration and body mass index phenotypes with mortality and obesity-related morbidities.","authors":"Xiaomin Zeng, Ruiye Chen, Danli Shi, Xiayin Zhang, Ting Su, Yaxin Wang, Yijun Hu, Mingguang He, Honghua Yu, Xianwen Shang","doi":"10.1111/acel.14435","DOIUrl":"https://doi.org/10.1111/acel.14435","url":null,"abstract":"This study aims to investigate the association between metabolomic aging acceleration and body mass index (BMI) phenotypes with mortality and obesity-related morbidities (ORMs). 85,458 participants were included from the UK Biobank. Metabolomic age was determined using 168 metabolites. The Chronological Age-Adjusted Gap was used to define metabolomically younger (MY) or older (MO) status. BMI categories were defined as normal weight, overweight, and obese. Participants were categorized into MY normal weight (MY-NW, reference), MY overweight (MY-OW), MY obesity (MY-OB), MO normal weight (MO-NW), MO overweight (MO-OW), and MO obesity (MO-OB). Mortality and 43 ORMs were identified through death registries and hospitalization records. Compared with MY-NW phenotype, MO-OB phenotype yielded increased risk of mortality and 32 ORMs, followed by MO-OW with mortality and 27 ORMs, MY-OB with mortality and 26 ORMs, MY-OW with 21 ORMs, and MO-NW with mortality and 14 ORMs. Consistently, MO-OB phenotype showed the highest risk of developing obesity-related multimorbidities, followed by MY-OB phenotype, MO-OW phenotype, MY-OW phenotype, and MO-NW phenotype. Additive interactions were found between metabolomic aging acceleration and obesity on CVD-specific mortality and 10 ORMs. Additionally, individuals with metabolomic aging acceleration had higher mortality and cardiovascular risk, even within the same BMI category. These findings suggest that metabolomic aging acceleration could help stratify mortality and ORMs risk across different BMI categories. Weight management should also be extended to individuals with overweight or obesity even in the absence of accelerated metabolomic aging, as they face increased healthy risk compared with MY-NW individuals. Additionally, delaying metabolic aging acceleration is needed for all metabolomically older groups, including those with normal weight.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14435"},"PeriodicalIF":8.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811497","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

Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice. 端粒酶逆转录酶基因敲入可以延长小鼠寿命，加速损伤修复。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-11 DOI: 10.1111/acel.14445

Tian-Yi Zhu, Po Hu, Yu-Hui Mi, Jun-Li Zhang, An-Na Xu, Ming-Tong Gao, Ying-Ying Zhang, San-Bing Shen, Guang-Ming Yang, Yang Pan

{"title":"Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice.","authors":"Tian-Yi Zhu, Po Hu, Yu-Hui Mi, Jun-Li Zhang, An-Na Xu, Ming-Tong Gao, Ying-Ying Zhang, San-Bing Shen, Guang-Ming Yang, Yang Pan","doi":"10.1111/acel.14445","DOIUrl":"https://doi.org/10.1111/acel.14445","url":null,"abstract":"While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise gene targeting into the Rosa26 locus via embryonic stem (ES) cells under the control of the elongation factor 1α (EF1α) promoter. The Tert knock-in (TertKI) mice harboring the EF1α-Tert gene displayed elevated telomerase activity, elongated telomeres, and extended lifespan, with no spontaneous genotoxicity or carcinogenicity. The TertKI mice showed also enhanced wound healing, characterized by significantly increased expression of Fgf7, Vegf, and collagen. Additionally, TertKI mice exhibited robust resistance to the progression of colitis induced by dextran sodium sulfate (DSS), accompanied by reduced expression of disease-deteriorating genes. These findings foreshadow the potential of TertKI as an extraordinary rejuvenation force, promising not only longevity but also rejuvenation in skin and intestinal aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14445"},"PeriodicalIF":8.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805541","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

Associations of combined accelerated biological aging and genetic susceptibility with incidence of heart failure in a population-based cohort study. 在一项基于人群的队列研究中，联合加速生物衰老和遗传易感性与心力衰竭发病率的关系。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-11 DOI: 10.1111/acel.14430

Hao Zhao, Xuening Zhang, Yanzhi Li, Wanxin Wang, Wenjian Lai, Wenjing Zhang, Kai Kang, Xiali Zhong, Lan Guo

{"title":"Associations of combined accelerated biological aging and genetic susceptibility with incidence of heart failure in a population-based cohort study.","authors":"Hao Zhao, Xuening Zhang, Yanzhi Li, Wanxin Wang, Wenjian Lai, Wenjing Zhang, Kai Kang, Xiali Zhong, Lan Guo","doi":"10.1111/acel.14430","DOIUrl":"https://doi.org/10.1111/acel.14430","url":null,"abstract":"The global aging population raises concerns about heart failure (HF), yet its association with accelerated biological age (BA) remains inadequately understood. We aimed to examine the longitudinal association between BA acceleration and incident HF risk, assess its modifying effect on genetic susceptibility, and how much BA acceleration mediates the impact of modifiable health behaviors on incident HF. We analyzed 274,608 UK Biobank participants without HF at baseline. Two BA accelerations (Biological Age Acceleration [BioAgeAccel] and Phenotypic Age Acceleration [PhenoAgeAccel]) were calculated by regressing clinical biomarker-based BA on chronological age, with higher values indicating accelerated aging. Health behavior scores were computed based on diet, physical activity, tobacco/nicotine, sleep, and BMI. Genetic risk scores (GRS) were calculated by 12 HF-associated loci. During a median follow-up of 13.5 years, 8915 HF cases were documented. Each standard deviation increase in BioAgeAccel and PhenoAgeAccel was associated with an increased incident HF risk, yielding HRs of 1.45 (95% CI, 1.42-1.48) and 1.42 (95% CI, 1.40-1.45), respectively. Participants with high GRS and highest quartile of BioAgeAccel had an HR of 2.69 (95% CI, 2.42-2.99), and for PhenoAgeAccel, an HR of 2.83 (95% CI, 2.52-3.18), compared to those with low GRS, and lowest quartile. Additive interactions were observed between GRS and BA accelerations. Health behaviors reduced HF risk, with 21.1% (95% CI, 19.5%-22.8%) mediated by decreased BioAgeAccel and 20.9% (95% CI, 19.5%-22.6%) by decreased PhenoAgeAccel. Accelerated BA is associated with an increased incident HF risk, with an additive effect when combined with genetic susceptibility. Maintaining health behaviors may help mitigate BA aging and reduce HF risk.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14430"},"PeriodicalIF":8.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811508","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

Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice. 雌二醇缺乏是衰老导致的雌性小鼠卫星细胞池耗竭的原因之一。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-06 DOI: 10.1111/acel.14441

Brian P Sullivan, Alexie A Larson, Ahmed S Shams, Shawna L McMillin, Mara C Ebeling, Sydney Peng, Michael Kyba, Dawn A Lowe

{"title":"Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice.","authors":"Brian P Sullivan, Alexie A Larson, Ahmed S Shams, Shawna L McMillin, Mara C Ebeling, Sydney Peng, Michael Kyba, Dawn A Lowe","doi":"10.1111/acel.14441","DOIUrl":"10.1111/acel.14441","url":null,"abstract":"The effects of aging on the satellite cell pool have primarily been studied in male mice, where the role of cell-intrinsic versus environmental changes on satellite cell function remains contentious. Estradiol is necessary for maintenance of satellite cell pool size in adult female mice-here we investigate the hypothesis that in females, estradiol is a major environmental driver of age-associated effects on satellite cells. In 24-26 month-old ovarian senescent mice, we find the satellite cell pool size is severely diminished in certain muscles (TA and EDL) but only marginally affected in others (soleus and gastrocnemius). Supplementation with 17-beta estradiol significantly increases satellite cell pool size in the TA and EDL. To assess cell-intrinsic versus environmental regulation, we perform two transplantation experiments, Adult or Aged satellite cells transplanted into Adult recipients, and Adult satellite cells transplanted into Adult or Aged mice. These results demonstrate that the aged environment dominates over cell-autonomous age in terms of the specification of satellite cell pool size. Transcriptional profiling on satellite cells from Adult, Aged and ovariectomized mice revealed commonalities across the two estradiol-deficient conditions, Aged and ovariectomized, in GO terms from differentially expressed genes. Our findings support the hypothesis that the lack of estradiol contributes to reductions in satellite cell number in Aged female muscle, yet cells that remain are functional in terms of proliferative potential and self-renewal capacity. These findings have implications for sex hormone treatment of menopausal women and highlight the vital role of estradiol in the maintenance of the satellite cell pool.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14441"},"PeriodicalIF":8.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783443","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

IF 8 1区医学

Aging Cell Pub Date : 2024-12-06 DOI: 10.1111/acel.14428

Matthew C Mosley, Holly E Kinser, Olivier M F Martin, Nicholas Stroustrup, Tim Schedl, Kerry Kornfeld, Zachary Pincus

{"title":"Similarities and differences in the gene expression signatures of physiological age versus future lifespan.","authors":"Matthew C Mosley, Holly E Kinser, Olivier M F Martin, Nicholas Stroustrup, Tim Schedl, Kerry Kornfeld, Zachary Pincus","doi":"10.1111/acel.14428","DOIUrl":"https://doi.org/10.1111/acel.14428","url":null,"abstract":"Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan-predictive biomarkers to isolate, at mid-adulthood, prospectively long- and short-lived individuals from an otherwise identical population. We selected two biomarkers which correlated positively with lifespan, lin-4p::GFP and mir-243p::GFP, and two which correlated negatively, mir-240/786p::GFP and autofluorescence. The gene-expression signature of long versus short future lifespan was strikingly similar across all four biomarkers tested. Since these biomarkers are expressed in different tissues, these results suggest a shared connection to a global health state correlated with future lifespan. To further investigate this underlying state, we compared the transcriptional signature of long versus short future lifespan to that of chronologically young versus old individuals. By comparison to a high-resolution time series of the average aging transcriptome, we determined that subpopulations predicted to be long- or short-lived by biomarker expression had significantly different transcriptional ages despite their shared chronological age. We found that this difference in apparent transcriptional age accounted for the majority of differentially expressed genes associated with future lifespan. Interestingly, we also identified several genes whose expression consistently separated samples by biomarker expression independent of apparent transcriptional age. These results suggest that the commonalities in the long-lived versus short-lived state reported across different biomarkers of aging extends beyond simply transcriptionally young versus transcriptionally old.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14428"},"PeriodicalIF":8.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783423","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

Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity. 己基神经酰胺和醚连接的磷酸胆碱作为人类极端长寿的标志的表型上调。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-05 DOI: 10.1111/acel.14429

Anna Fernàndez-Bernal, Joaquim Sol, José Daniel Galo-Licona, Natàlia Mota-Martorell, Cristina Mas-Bargues, Ángel Belenguer-Varea, Èlia Obis, José Viña, Consuelo Borrás, Mariona Jové, Reinald Pamplona

{"title":"Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity.","authors":"Anna Fernàndez-Bernal, Joaquim Sol, José Daniel Galo-Licona, Natàlia Mota-Martorell, Cristina Mas-Bargues, Ángel Belenguer-Varea, Èlia Obis, José Viña, Consuelo Borrás, Mariona Jové, Reinald Pamplona","doi":"10.1111/acel.14429","DOIUrl":"https://doi.org/10.1111/acel.14429","url":null,"abstract":"Centenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this lipidomic profile is specific to centenarians or is the consequence of extreme longevity genetics and is also present in centenarians' offspring. This distinction is crucial for defining potential therapeutic targets that could help delay the aging process and associated pathologies. We applied mass-spectrometry-based techniques to quantify 569 lipid species in plasma samples from 39 centenarians, 63 centenarians' offspring, and 69 noncentenarians' offspring without familial connections. Based on this profile, we calculated different indexes to characterize the functional and structural properties of plasma lipidome. Our findings demonstrate that extreme longevity genetics (centenarians and centenarians' offspring) determines a specific lipidomic signature characterized by (i) an enrichment of hexosylceramides, (ii) a decrease of specific species of ceramides and sulfatides, (iii) a global increase of ether-PC and ether-LPC, and (iv) changes in the fluidity and diversity of specific lipid classes. We point out the conversion of ceramides to hexosylceramides and the maintenance of the levels of the ether-linked PC as a phenotypic trait to guarantee extreme longevity. We propose that this molecular signature is the result of an intrinsic adaptive program that preserves protective mechanisms and cellular identity.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14429"},"PeriodicalIF":8.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783420","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

Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice. 肠道菌群代谢支链氨基酸及其代谢物可改善衰老小鼠的生理功能。

IF 8 1区医学

Aging Cell Pub Date : 2024-12-04 DOI: 10.1111/acel.14434

Hongchao Wang, Ling Feng, Zhangming Pei, Jianxin Zhao, Shourong Lu, Wenwei Lu

{"title":"Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice.","authors":"Hongchao Wang, Ling Feng, Zhangming Pei, Jianxin Zhao, Shourong Lu, Wenwei Lu","doi":"10.1111/acel.14434","DOIUrl":"https://doi.org/10.1111/acel.14434","url":null,"abstract":"The metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice. The results showed that these treatments could delay aging in mice by providing health benefits in reducing oxidative stress and inflammation, improving muscle capacity, reversing brain acetylcholine levels, and regulating blood glucose. The mechanism was preliminarily explored by combining the gut microbiota metagenome and faecal serum metabolome. Parabacteroides merdae altered the species composition and structure of the gut microbiota in mice. Increasing the abundance of beneficial bacteria, such as Bifidobacterium pseudolongum. Three metabolites affects the gut microbiota and the body's pathways of protein and improves the overall health through a variety of signaling pathways. Overall, regulating the gut microbiota involved in branched-chain amino acid metabolism to bring health benefits may be a new way of reversing aging.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14434"},"PeriodicalIF":8.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765049","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

Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study. 加速生物老化、健康行为和遗传易感性与脑卒中及其亚型的发病率：一项前瞻性队列研究

IF 8 1区医学

Aging Cell Pub Date : 2024-12-04 DOI: 10.1111/acel.14427

Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu

{"title":"Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study.","authors":"Xuening Zhang, Hao Zhao, Zilin Li, Xinjie Liu, Yurong Zhang, Ning Yang, Tongchao Zhang, Xiaorong Yang, Ming Lu","doi":"10.1111/acel.14427","DOIUrl":"https://doi.org/10.1111/acel.14427","url":null,"abstract":"Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA acceleration calculated by regressing BA on chronological age. The polygenic risk score (PRS) was derived from 87 genetic loci. The behaviors score was based on diet, physical activity, tobacco/nicotine, sleep, and BMI. During a median follow-up of 13.6 years, 5460 strokes, 4337 ischemic stroke (IS), 951 intracerebral hemorrhage (ICH), and 553 subarachnoid hemorrhage (SAH) cases were documented. Adjusting for confounding factors, each standard deviation increase in BA acceleration was associated with higher stroke risk: for KDM-BA acceleration, stroke (HR = 1.28, 95% CI = 1.25-1.32), IS (1.32, 1.28-1.36), ICH (1.15, 1.08-1.23), and SAH (1.16, 1.07-1.27); for PhenoAge acceleration, stroke (1.22, 1.19-1.25), IS (1.26, 1.22-1.29), ICH (1.08, 1.02-1.16), and SAH (1.08, 1.00-1.18). Compared to participants with the lowest PRS and BA acceleration, those with the highest PRS and BA acceleration had the highest stroke risk (KDM-BA acceleration: 2.19, 1.85-2.59; PhenoAge acceleration: 2.03, 1.69-2.42). Additionally, there was an additive interaction between KDM-BA acceleration and PRS. The mediation proportion of BA acceleration in associations of behaviors score with incident stroke and its subtypes ranged from 15.84% to 33.08%. BA acceleration may raise stroke risk, especially in those with high genetic risk. Maintaining healthy behaviors may help mitigate this risk.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14427"},"PeriodicalIF":8.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778681","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