Aging Cell最新文献_第2页

Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics.

IF 8 1区医学

Aging Cell Pub Date : 2024-12-07 DOI: 10.1111/acel.14399

Iman M Al-Naggar, Maria Antony, Dylan Baker, Lichao Wang, Lucas Da Cunha Godoy, Chia-Ling Kuo, Matthew O Fraser, Phillip P Smith, Ming Xu, George A Kuchel

{"title":"Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics.","authors":"Iman M Al-Naggar, Maria Antony, Dylan Baker, Lichao Wang, Lucas Da Cunha Godoy, Chia-Ling Kuo, Matthew O Fraser, Phillip P Smith, Ming Xu, George A Kuchel","doi":"10.1111/acel.14399","DOIUrl":"https://doi.org/10.1111/acel.14399","url":null,"abstract":"Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging-related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy-induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high-fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD-induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine-blood barrier.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14399"},"PeriodicalIF":8.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790522","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.

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":"https://doi.org/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

Similarities and differences in the gene expression signatures of physiological age versus future lifespan.

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.

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.

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.

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

Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity.

IF 8 1区医学

Aging Cell Pub Date : 2024-12-04 DOI: 10.1111/acel.14386

Richie P Goulding, Braeden T Charlton, Ellen A Breedveld, Matthijs van der Laan, Anne R Strating, Wendy Noort, Aryna Kolodyazhna, Brent Appelman, Michèle van Vugt, Anita E Grootemaat, Nicole N van der Wel, Jos J de Koning, Frank W Bloemers, Rob C I Wüst

{"title":"Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity.","authors":"Richie P Goulding, Braeden T Charlton, Ellen A Breedveld, Matthijs van der Laan, Anne R Strating, Wendy Noort, Aryna Kolodyazhna, Brent Appelman, Michèle van Vugt, Anita E Grootemaat, Nicole N van der Wel, Jos J de Koning, Frank W Bloemers, Rob C I Wüst","doi":"10.1111/acel.14386","DOIUrl":"https://doi.org/10.1111/acel.14386","url":null,"abstract":"Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals. Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle-aged: 99 ± 27 pmol O2.s-1.mg-1, p = 0.95) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle-aged: 5.68 ± 1.48%, p = 0.25), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle-aged: 1.55 ± 0.15 A.U., p < 0.0001), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle-aged: 13.55 ± 4.10%, p = 0.002) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle-aged: 13.92 ± 4.95%, p = 0.005). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density. Collectively, our work highlights the critical role of skeletal muscle mitochondria in age-associated declines in physical function.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14386"},"PeriodicalIF":8.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765053","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

Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements.

IF 8 1区医学

Aging Cell Pub Date : 2024-12-01 DOI: 10.1111/acel.14431

Lucy Sinke, Marian Beekman, Yotam Raz, Thies Gehrmann, Ioannis Moustakas, Alexis Boulinguiez, Nico Lakenberg, Eka Suchiman, Fatih A Bogaards, Daniele Bizzarri, Erik B van den Akker, Melanie Waldenberger, Gillian Butler-Browne, Capucine Trollet, C P G M de Groot, Bastiaan T Heijmans, P Eline Slagboom

{"title":"Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements.","authors":"Lucy Sinke, Marian Beekman, Yotam Raz, Thies Gehrmann, Ioannis Moustakas, Alexis Boulinguiez, Nico Lakenberg, Eka Suchiman, Fatih A Bogaards, Daniele Bizzarri, Erik B van den Akker, Melanie Waldenberger, Gillian Butler-Browne, Capucine Trollet, C P G M de Groot, Bastiaan T Heijmans, P Eline Slagboom","doi":"10.1111/acel.14431","DOIUrl":"https://doi.org/10.1111/acel.14431","url":null,"abstract":"Across the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue-specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes. The Growing Old Together (GOTO) study is a 13-week lifestyle intervention in older adults, which imparted health benefits to participants. Here, we characterize the DNA methylation response to this intervention at over 750 thousand CpGs in muscle, adipose, and blood. Differentially methylated sites are enriched for active chromatin states, located close to relevant transcription factor binding sites, and associated with changing expression of insulin sensitivity genes and health parameters. In addition, measures of biological age are consistently reduced, with decreases in grimAge associated with observed health improvements. Taken together, our results identify responsive molecular markers and demonstrate their potential to measure progression and finetune treatment of age-related risks and diseases.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14431"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765094","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

The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model.

IF 8 1区医学

Aging Cell Pub Date : 2024-11-29 DOI: 10.1111/acel.14436

Jin Liu, Yi Liu, Chao Gao, Hong Pan, Pei Huang, Yuyan Tan, Shengdi Chen

{"title":"The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model.","authors":"Jin Liu, Yi Liu, Chao Gao, Hong Pan, Pei Huang, Yuyan Tan, Shengdi Chen","doi":"10.1111/acel.14436","DOIUrl":"https://doi.org/10.1111/acel.14436","url":null,"abstract":"Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. In MPTP-treated mice, transmission electron microscopy was applied for MAM ultrastructural visualization. Nano ultra-high performance liquid chromatography-tandem mass spectrum and bioinformatic analysis were adopted to obtain underlying molecular data of MAM fractions. The loosened, shortened and reduced MAM tethering was found in substantia nigral neurons from MPTP-treated mice. In midbrain MAM proteomics, 158 differentially expressed proteins (DEPs) were identified between two groups. Specific DEPs were validated by western blot and exhibited significantly statistical changes, aligning with proteomic results. Bioinformatic analysis indicated that membrane, cytoplasm and cell projection were three major localizations for DEPs. Biological processes including metabolism, lipid transport, and immunological and apoptotic signaling pathways were greatly affected. For consensus MAM proteins, the enriched pathway analysis revealed the potential relationship between neurodegenerative diseases and MAM. Several biological processes such as peroxisome function and clathrin-mediated endocytosis, were clustered, which provided additional insights into the fundamental molecular pathways associated with MAM. In our study, we demonstrated disrupted ER-mitochondria contacts in an MPTP-induced PD mouse model. The underlying signatures of MAM were revealed by proteomics and bioinformatic analysis, providing valuable insights into its potential role in PD pathogenesis.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14436"},"PeriodicalIF":8.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754368","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

Restoration of hair follicle inductive properties by depletion of senescent cells.

IF 8 1区医学

Aging Cell Pub Date : 2024-11-29 DOI: 10.1111/acel.14353

Alberto Pappalardo, Jin Yong Kim, Hasan Erbil Abaci, Angela M Christiano

{"title":"Restoration of hair follicle inductive properties by depletion of senescent cells.","authors":"Alberto Pappalardo, Jin Yong Kim, Hasan Erbil Abaci, Angela M Christiano","doi":"10.1111/acel.14353","DOIUrl":"https://doi.org/10.1111/acel.14353","url":null,"abstract":"Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP-mediated repressive interactions in human DP culture, resulting in an increased Wnt-active cell population. In hair reconstitution assays, senolytic-depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic-depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell-based therapies.","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14353"},"PeriodicalIF":8.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754367","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