npj Aging最新文献

{"title":"Accelerated epigenetic aging and decreased natural killer cells based on DNA methylation in patients with untreated major depressive disorder.","authors":"Ryota Shindo, Takaki Tanifuji, Satoshi Okazaki, Ikuo Otsuka, Toshiyuki Shirai, Kentaro Mouri, Tadasu Horai, Akitoyo Hishimoto","doi":"10.1038/s41514-023-00117-1","DOIUrl":"10.1038/s41514-023-00117-1","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189338","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":"Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.","authors":"Jun Yuan,&nbsp;Steve Pedrini,&nbsp;Rohith Thota,&nbsp;James Doecke,&nbsp;Pratishtha Chatterjee,&nbsp;Hamid R Sohrabi,&nbsp;Charlotte E Teunissen,&nbsp;Inge M W Verberk,&nbsp;Erik Stoops,&nbsp;Hugo Vanderstichele,&nbsp;Bruno P Meloni,&nbsp;Christopher Mitchell,&nbsp;Stephanie Rainey-Smith,&nbsp;Kathryn Goozee,&nbsp;Andrew Chi Pang Tai,&nbsp;Nicholas Ashton,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Junjie Gao,&nbsp;Delin Liu,&nbsp;Frank Mastaglia,&nbsp;Charles Inderjeeth,&nbsp;Minghao Zheng,&nbsp;Ralph N Martins","doi":"10.1038/s41514-023-00114-4","DOIUrl":"https://doi.org/10.1038/s41514-023-00114-4","url":null,"abstract":"<p><p>Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ- (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including Aβ40, Aβ42, Aβ42/Aβ40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the Aβ+ group (71.49 ± 25.00 pmol/L) compared with the Aβ- group (56.51 ± 22.14 pmol/L) (P < 0.01). Moreover, Spearman's correlation analysis showed that plasma SOST concentrations were positively correlated with brain Aβ load (ρ = 0.321, P = 0.001). Importantly, plasma SOST combined with Aβ42/Aβ40 ratio significantly increased the area under the curve (AUC) when compared with using Aβ42/Aβ40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167871","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":"Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.","authors":"Dennyson Leandro M Fonseca, Igor Salerno Filgueiras, Alexandre H C Marques, Elroy Vojdani, Gilad Halpert, Yuri Ostrinski, Gabriela Crispim Baiocchi, Desirée Rodrigues Plaça, Paula P Freire, Shahab Zaki Pour, Guido Moll, Rusan Catar, Yael Bublil Lavi, Jonathan I Silverberg, Jason Zimmerman, Gustavo Cabral-Miranda, Robson F Carvalho, Taj Ali Khan, Harald Heidecke, Rodrigo J S Dalmolin, Andre Ducati Luchessi, Hans D Ochs, Lena F Schimke, Howard Amital, Gabriela Riemekasten, Israel Zyskind, Avi Z Rosenberg, Aristo Vojdani, Yehuda Shoenfeld, Otavio Cabral-Marques","doi":"10.1038/s41514-023-00118-0","DOIUrl":"10.1038/s41514-023-00118-0","url":null,"abstract":"<p><p>Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10083556","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":"Mitochonic acid 5 attenuates age-related neuromuscular dysfunction associated with mitochondrial Ca²⁺ overload in Caenorhabditis elegans.","authors":"XinTong Wu,&nbsp;Miku Seida,&nbsp;Takaaki Abe,&nbsp;Atsushi Higashitani","doi":"10.1038/s41514-023-00116-2","DOIUrl":"https://doi.org/10.1038/s41514-023-00116-2","url":null,"abstract":"<p><p>Mitochonic acid-5 ameliorates the pathophysiology of human mitochondrial-disease fibroblasts and Caenorhabditis elegans Duchenne muscular dystrophy and Parkinson's disease models. Here, we found that 10 μM MA-5 attenuates the age-related decline in motor performance, loss of muscle mitochondria, and degeneration of dopaminergic neurons associated with mitochondrial Ca²⁺ overload in C. elegans. These findings suggest that MA-5 may act as an anti-aging agent against a wide range of neuromuscular dysfunctions in metazoans.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934807","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":"Unbiased proteomics and multivariable regularized regression techniques identify SMOC1, NOG, APCS, and NTN1 in an Alzheimer's disease brain proteomic signature.","authors":"Jackson A Roberts, Vijay R Varma, Julián Candia, Toshiko Tanaka, Luigi Ferrucci, David A Bennett, Madhav Thambisetty","doi":"10.1038/s41514-023-00112-6","DOIUrl":"10.1038/s41514-023-00112-6","url":null,"abstract":"<p><p>Advancements in omics methodologies have generated a wealth of high-dimensional Alzheimer's disease (AD) datasets, creating significant opportunities and challenges for data interpretation. In this study, we utilized multivariable regularized regression techniques to identify a reduced set of proteins that could discriminate between AD and cognitively normal (CN) brain samples. Utilizing eNetXplorer, an R package that tests the accuracy and significance of a family of elastic net generalized linear models, we identified 4 proteins (SMOC1, NOG, APCS, NTN1) that accurately discriminated between AD (n = 31) and CN (n = 22) middle frontal gyrus (MFG) tissue samples from Religious Orders Study participants with 83 percent accuracy. We then validated this signature in MFG samples from Baltimore Longitudinal Study of Aging participants using leave-one-out logistic regression cross-validation, finding that the signature again accurately discriminated AD (n = 31) and CN (n = 19) participants with a receiver operating characteristic curve area under the curve of 0.863. These proteins were strongly correlated with the burden of neurofibrillary tangle and amyloid pathology in both study cohorts. We additionally tested whether these proteins differed between AD and CN inferior temporal gyrus (ITG) samples and blood serum samples at the time of AD diagnosis in ROS and BLSA, finding that the proteins differed between AD and CN ITG samples but not in blood serum samples. The identified proteins may provide mechanistic insights into the pathophysiology of AD, and the methods utilized in this study may serve as the basis for further work with additional high-dimensional datasets in AD.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802443","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":"Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity.","authors":"Mei ElGindi,&nbsp;Jiranuwat Sapudom,&nbsp;Anna Garcia Sabate,&nbsp;Brian Chesney Quartey,&nbsp;Aseel Alatoom,&nbsp;Mohamed Al-Sayegh,&nbsp;Rui Li,&nbsp;Weiqiang Chen,&nbsp;Jeremy Teo","doi":"10.1038/s41514-023-00111-7","DOIUrl":"https://doi.org/10.1038/s41514-023-00111-7","url":null,"abstract":"<p><p>Microgravity accelerates the aging of various physiological systems, and it is well acknowledged that aged individuals and astronauts both have increased susceptibility to infections and poor response to vaccination. Immunologically, dendritic cells (DCs) are the key players in linking innate and adaptive immune responses. Their distinct and optimized differentiation and maturation phases play a critical role in presenting antigens and mounting effective lymphocyte responses for long-term immunity. Despite their importance, no studies to date have effectively investigated the effects of microgravity on DCs in their native microenvironment, which is primarily located within tissues. Here, we address a significantly outstanding research gap by examining the effects of simulated microgravity via a random positioning machine on both immature and mature DCs cultured in biomimetic collagen hydrogels, a surrogate for tissue matrices. Furthermore, we explored the effects of loose and dense tissues via differences in collagen concentration. Under these various environmental conditions, the DC phenotype was characterized using surface markers, cytokines, function, and transcriptomic profiles. Our data indicate that aged or loose tissue and exposure to RPM-induced simulated microgravity both independently alter the immunogenicity of immature and mature DCs. Interestingly, cells cultured in denser matrices experience fewer effects of simulated microgravity at the transcriptome level. Our findings are a step forward to better facilitate healthier future space travel and enhance our understanding of the aging immune system on Earth.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745056","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":"Biomarkers selection and mathematical modeling in biological age estimation.","authors":"Solim Essomandan Clémence Bafei,&nbsp;Chong Shen","doi":"10.1038/s41514-023-00110-8","DOIUrl":"https://doi.org/10.1038/s41514-023-00110-8","url":null,"abstract":"<p><p>Biological age (BA) is important for clinical monitoring and preventing aging-related disorders and disabilities. Clinical and/or cellular biomarkers are measured and integrated in years using mathematical models to display an individual's BA. To date, there is not yet a single or set of biomarker(s) and technique(s) that is validated as providing the BA that reflects the best real aging status of individuals. Herein, a comprehensive overview of aging biomarkers is provided and the potential of genetic variations as proxy indicators of the aging state is highlighted. A comprehensive overview of BA estimation methods is also provided as well as a discussion of their performances, advantages, limitations, and potential approaches to overcome these limitations.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799836","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":"Author Correction: Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction.","authors":"Rachael E Redgrave,&nbsp;Emily Dookun,&nbsp;Laura K Booth,&nbsp;Maria Camacho Encina,&nbsp;Omowumi Folaranmi,&nbsp;Simon Tual-Chalot,&nbsp;Jason H Gill,&nbsp;W Andrew Owens,&nbsp;Ioakim Spyridopoulos,&nbsp;João F Passos,&nbsp;Gavin D Richardson","doi":"10.1038/s41514-023-00115-3","DOIUrl":"https://doi.org/10.1038/s41514-023-00115-3","url":null,"abstract":"","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713658","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":"Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction.","authors":"Rachael E Redgrave, Emily Dookun, Laura K Booth, Maria Camacho Encina, Omowumi Folaranmi, Simon Tual-Chalot, Jason H Gill, W Andrew Owens, Ioakim Spyridopoulos, João F Passos, Gavin D Richardson","doi":"10.1038/s41514-023-00113-5","DOIUrl":"10.1038/s41514-023-00113-5","url":null,"abstract":"<p><p>Myocardial infarction is a leading cause of morbidity and mortality. While reperfusion is now standard therapy, pathological remodelling leading to heart failure remains a clinical problem. Cellular senescence has been shown to contribute to disease pathophysiology and treatment with the senolytic navitoclax attenuates inflammation, reduces adverse myocardial remodelling and results in improved functional recovery. However, it remains unclear which senescent cell populations contribute to these processes. To identify whether senescent cardiomyocytes contribute to disease pathophysiology post-myocardial infarction, we established a transgenic model in which p16 (CDKN2A) expression was specifically knocked-out in the cardiomyocyte population. Following myocardial infarction, mice lacking cardiomyocyte p16 expression demonstrated no difference in cardiomyocyte hypertrophy but exhibited improved cardiac function and significantly reduced scar size in comparison to control animals. This data demonstrates that senescent cardiomyocytes participate in pathological myocardial remodelling. Importantly, inhibition of cardiomyocyte senescence led to reduced senescence-associated inflammation and decreased senescence-associated markers within other myocardial lineages, consistent with the hypothesis that cardiomyocytes promote pathological remodelling by spreading senescence to other cell-types. Collectively this study presents the demonstration that senescent cardiomyocytes are major contributors to myocardial remodelling and dysfunction following a myocardial infarction. Therefore, to maximise the potential for clinical translation, it is important to further understand the mechanisms underlying cardiomyocyte senescence and how to optimise senolytic strategies to target this cell lineage.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035332","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":"Ageing restructures the transcriptome of the hypothalamic supraoptic nucleus and alters the response to dehydration.","authors":"Ghadir Elsamad,&nbsp;André Souza Mecawi,&nbsp;Audrys G Pauža,&nbsp;Benjamin Gillard,&nbsp;Alex Paterson,&nbsp;Victor J Duque,&nbsp;Olivera Šarenac,&nbsp;Nina Japundžić Žigon,&nbsp;Mingkwan Greenwood,&nbsp;Michael P Greenwood,&nbsp;David Murphy","doi":"10.1038/s41514-023-00108-2","DOIUrl":"https://doi.org/10.1038/s41514-023-00108-2","url":null,"abstract":"<p><p>Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible to dehydration. Chronically, vasopressin has been associated with numerous diseases of old age, including type 2 diabetes and metabolic syndrome. Bulk RNAseq transcriptome analysis has been used to catalogue the polyadenylated supraoptic nucleus transcriptomes of adult (3 months) and aged (18 months) rats in basal euhydrated and stimulated dehydrated conditions. Gene ontology and Weighted Correlation Network Analysis revealed that ageing is associated with alterations in the expression of extracellular matrix genes. Interestingly, whilst the transcriptomic response to dehydration is overall blunted in aged animals compared to adults, there is a specific enrichment of differentially expressed genes related to neurodegenerative processes in the aged cohort, suggesting that dehydration itself may provoke degenerative consequences in aged rats.</p>","PeriodicalId":19348,"journal":{"name":"npj Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511488","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}