Frontiers in aging最新文献

{"title":"Editorial: Women in aging and the immune system.","authors":"Jenna M Bartley, Anshu Agrawal","doi":"10.3389/fragi.2024.1386626","DOIUrl":"https://doi.org/10.3389/fragi.2024.1386626","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1386626"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178001","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":"Editorial: Effects of vascular function and aging on brain circulation and neurodegeneration.","authors":"Benjamin Petersen, Sharon Negri, Madison Milan, Helen Shi, Zeke Reyff, Cade Ballard, Jennifer Ihuoma, Andrea Di Francesco, Stefano Tarantini","doi":"10.3389/fragi.2024.1385066","DOIUrl":"https://doi.org/10.3389/fragi.2024.1385066","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1385066"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178000","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":"Alterations in metabolic pathways: a bridge between aging and weaker innate immune response.","authors":"Zahra Saleh, Sara Mirzazadeh, Fatemeh Mirzaei, Kamran Heidarnejad, Seppo Meri, Kurosh Kalantar","doi":"10.3389/fragi.2024.1358330","DOIUrl":"https://doi.org/10.3389/fragi.2024.1358330","url":null,"abstract":"<p><p>Aging is a time-dependent progressive physiological process, which results in impaired immune system function. Age-related changes in immune function increase the susceptibility to many diseases such as infections, autoimmune diseases, and cancer. Different metabolic pathways including glycolysis, tricarboxylic acid cycle, amino acid metabolism, pentose phosphate pathway, fatty acid oxidation and fatty acid synthesis regulate the development, differentiation, and response of adaptive and innate immune cells. During aging all these pathways change in the immune cells. In addition to the changes in metabolic pathways, the function and structure of mitochondria also have changed in the immune cells. Thereby, we will review changes in the metabolism of different innate immune cells during the aging process.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1358330"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177998","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":"Disrupting the SKN-1 homeostat: mechanistic insights and phenotypic outcomes.","authors":"Chris D Turner, Carmen M Ramos, Sean P Curran","doi":"10.3389/fragi.2024.1369740","DOIUrl":"10.3389/fragi.2024.1369740","url":null,"abstract":"<p><p>The mechanisms that govern maintenance of cellular homeostasis are crucial to the lifespan and healthspan of all living systems. As an organism ages, there is a gradual decline in cellular homeostasis that leads to senescence and death. As an organism lives into advanced age, the cells within will attempt to abate age-related decline by enhancing the activity of cellular stress pathways. The regulation of cellular stress responses by transcription factors SKN-1/Nrf2 is a well characterized pathway in which cellular stress, particularly xenobiotic stress, is abated by SKN-1/Nrf2-mediated transcriptional activation of the Phase II detoxification pathway. However, SKN-1/Nrf2 also regulates a multitude of other processes including development, pathogenic stress responses, proteostasis, and lipid metabolism. While this process is typically tightly regulated, constitutive activation of SKN-1/Nrf2 is detrimental to organismal health, this raises interesting questions surrounding the tradeoff between SKN-1/Nrf2 cryoprotection and cellular health and the ability of cells to deactivate stress response pathways post stress. Recent work has determined that transcriptional programs of SKN-1 can be redirected or suppressed to abate negative health outcomes of constitutive activation. Here we will detail the mechanisms by which SKN-1 is controlled, which are important for our understanding of SKN-1/Nrf2 cytoprotection across the lifespan.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1369740"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159584","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":"Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice.","authors":"Christopher B Forsyth, Maliha Shaikh, Phillip A Engen, Fabian Preuss, Ankur Naqib, Breanna A Palmen, Stefan J Green, Lijuan Zhang, Zlata R Bogin, Kristi Lawrence, Deepak Sharma, Garth R Swanson, Faraz Bishehsari, Robin M Voigt, Ali Keshavarzian","doi":"10.3389/fragi.2024.1352299","DOIUrl":"10.3389/fragi.2024.1352299","url":null,"abstract":"<p><p><b>Introduction:</b> Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of \"inflammaging\" Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging. <b>Methods:</b> As a model of aging, C57BL/6J mice fecal (colonic) microbiota (16S) and isolated colonic crypt epithelial cell gene expression (RNA-seq) were assessed at 2 months (mth) (human: 18 years old; yo), 15 mth (human: 50 yo), and 25 mth (human: 84 yo). Informatics examined aging-related microbial compositions, differential colonic crypt epithelial cell gene expressions, and correlations between colonic bacteria and colonic crypt epithelial cell gene expressions. <b>Results:</b> Fecal microbiota exhibited significantly increased relative abundances of pro-inflammatory Gn bacteria with aging. Colonic crypt epithelial cell gene expression analysis showed significant age-related downregulation of key AMP genes that repress the growth of Gn bacteria. The aging-related decrease in AMP gene expressions is significantly correlated with an increased abundance in Gn bacteria (dysbiosis), loss of colonic barrier gene expression, and senescence- and inflammation-related gene expression. <b>Conclusion:</b> This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1352299"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10945560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159700","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":"Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin.","authors":"Cassandra Falckenhayn, Agata Bienkowska, Jörn Söhle, Katrin Wegner, Guenter Raddatz, Boris Kristof, Dirk Kuck, Ralf Siegner, Ronny Kaufmann, Julia Korn, Sascha Baumann, Daniela Lange, Andreas Schepky, Henry Völzke, Lars Kaderali, Marc Winnefeld, Frank Lyko, Elke Grönniger","doi":"10.3389/fragi.2023.1258184","DOIUrl":"10.3389/fragi.2023.1258184","url":null,"abstract":"<p><p>Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes <i>in vivo</i> and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"4 ","pages":"1258184"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159583","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":"How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.","authors":"Rachel Holmes, Hongzhe Duan, Olivia Bagley, Deqing Wu, Yury Loika, Alexander Kulminski, Anatoliy Yashin, Konstantin Arbeev, Svetlana Ukraintseva","doi":"10.3389/fragi.2024.1359202","DOIUrl":"10.3389/fragi.2024.1359202","url":null,"abstract":"<p><p>The ε4 allele of the APOE gene (<i>APOE4</i>) is known for its negative association with human longevity; however, the mechanism is unclear. <i>APOE4</i> is also linked to changes in body weight, and the latter changes were associated with survival in some studies. Here, we explore the role of aging changes in weight in the connection between <i>APOE4</i> and longevity using the causal mediation analysis (CMA) approach to uncover the mechanisms of genetic associations. Using the Health and Retirement Study (HRS) data, we tested a hypothesis of whether the association of <i>APOE4</i> with reduced survival to age 85+ is mediated by key characteristics of age trajectories of weight, such as the age at reaching peak values and the slope of the decline in weight afterward. Mediation effects were evaluated by the total effect (TE), natural indirect effect, and percentage mediated. The controlled direct effect and natural direct effect are also reported. The CMA results suggest that <i>APOE4</i> carriers have 19%-22% (TE <i>p</i> = 0.020-0.039) lower chances of surviving to age 85 and beyond, in part, because they reach peak values of weight at younger ages, and their weight declines faster afterward compared to non-carriers. This finding is in line with the idea that the detrimental effect of <i>APOE4</i> on longevity is, in part, related to the accelerated physical aging of ε4 carriers.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1359202"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145045","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":"Dietary pyrroloquinoline quinone hinders aging progression in male mice and D-galactose-induced cells.","authors":"Nur Syafiqah Mohamad Ishak, Midori Kikuchi, Kazuto Ikemoto","doi":"10.3389/fragi.2024.1351860","DOIUrl":"10.3389/fragi.2024.1351860","url":null,"abstract":"<p><p><b>Background:</b> Understanding and promoting healthy aging has become a necessity in the modern world, where life expectancy is rising. The prospective benefits of the antioxidant pyrroloquinoline quinone (PQQ) in healthy aging are promising. However, its role in aging remains unclear. Thus, this study aimed to investigate the effect of PQQ on preventing the progression of aging and to explore its underlying molecular mechanisms. <b>Methods:</b> Naturally aged C57BL/6J male mice were fed a normal diet with or without PQQ (20 mg/kg/day) for 10 weeks. Body composition was measured by bioimpedance at weeks 0 and 8. The integument conditions were evaluated at weeks 0, 4, and 8. Muscle strength and function were examined at week 8. At the ninth week, computed tomography images of the mice were captured, and blood and tissue samples were collected. The levels of inflammatory cytokines in the gastrocnemius muscle were measured, and the muscle fiber cross-sectional area in the soleus muscle was examined. Additionally, a D-galactose (D-gal)-induced cell aging model was used to study the effects of PQQ intervention on cell proliferation, senescence, differentiation, ROS levels, and mitochondrial function in myoblasts (C2C12). Cell proliferation and monolayer permeability of D-gal-induced intestinal epithelial cells (IEC6) were also examined. <b>Results:</b> Aged mice suffered from malnutrition; however, PQQ supplementation ameliorated this effect, possibly by improving metabolic dysfunction and small intestinal performance. PQQ prevented rapid loss of body fat and body fluid accumulation, attenuated muscle atrophy and weakening, reduced chronic inflammation in skeletal muscles, and improved skin and coating conditions in aged mice. Furthermore, PQQ intervention in D-gal-treated C2C12 cells improved mitochondrial function, reduced cellular reactive oxygen species (ROS) levels and senescence, and enhanced cell differentiation, consequently preventing age-related muscle atrophy. In addition, PQQ increased cell proliferation in D-gal-treated IEC6 cells and consequently improved intestinal barrier function. <b>Conclusion:</b> PQQ could hinder the aging process and particularly attenuate muscle atrophy, and muscle weakness by improving mitochondrial function, leading to reduced age-related oxidative stress and inflammation in muscles. PQQ may also ameliorate malnutrition caused by intestinal barrier dysfunction by enhancing IEC proliferation. This study provides evidence for the role of PQQ in aging and suggests that PQQ may be a potential nutritional supplementation that can be included in healthy aging strategies.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1351860"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133441","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":"Premature aging in genetic diseases: what conclusions can be drawn for physiological aging.","authors":"Filip Milosic, Markus Hengstschläger, Selma Osmanagic-Myers","doi":"10.3389/fragi.2023.1327833","DOIUrl":"10.3389/fragi.2023.1327833","url":null,"abstract":"<p><p>According to current views the major hallmarks of physiological aging may be subdivided into three categories, primary causes of cellular damage (genomic instability, telomere attrition, loss of proteostasis, epigenetic alterations and compromised macroautophagy), antagonistic hallmarks that represent response to damage (deregulated nutrient sensing, cellular senescence, mitochondrial dysfunction) and integrative hallmarks that represent culprits of the phenotype (stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis). In contrast to physiological aging, premature aging diseases are driven by one or two distinct primary causes of aging, such as genomic instability in the case of Werner syndrome (WS), each displaying other hallmarks of aging to a variable extent. In this review we will focus on primary causes of well-investigated premature aging diseases Hutchinson-Gilford progeria syndrome (HGPS), WS, and Cockayne syndrome (CS) and for each provide an overview of reported aging hallmarks to elucidate resemblance to physiological aging on the mechanistic level and in the context of characteristic age-related diseases. Ubiquitous and tissue specific animal models of premature aging diseases will be discussed as useful tools to decipher fundamental aging-related mechanisms and develop intervention strategies to combat premature aging and age-related diseases.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"4 ","pages":"1327833"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121527","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":"Auditory discrimination in aging bilinguals vs. monolinguals with and without hearing loss.","authors":"Miwako Hisagi, Beatriz Barragan, Arlene Diaz, Kai White, Margaret Winter","doi":"10.3389/fragi.2023.1302050","DOIUrl":"10.3389/fragi.2023.1302050","url":null,"abstract":"<p><p>Demands for effective assessments of speech perception specific to the aging brain are increasing, as the impacts of hearing loss on an individual's functional health, socialization, and cognition have become more widely recognized. Understanding the mechanisms behind the optimal function of the aging brain in relation to speech and language is challenging, especially in the bilingual population where the language learning and language interference processes could be mistaken for perceptual difficulty. Age-related presbycusis is unavoidable, and the contributions of this sensorineural hearing loss (SNHL) process on impaired speech recognition are not completely understood. This lack of understanding of the effects of aging and bilingual language competency on speech perception can act as a barrier to successful auditory rehabilitation. The present study investigated the effects of aging on vowel sound discrimination in adult listeners (age 50+) with the following characteristics: American English (AE) monolinguals with normal hearing, simultaneous or early sequential Spanish-English (SE) bilinguals with normal hearing, and AE monolinguals with SNHL (AE-SNHL). The goal was to identify the differences in vowel sound discrimination performance between the monolingual and bilingual aging populations to guide future language assessments and intervention processes. English vowel discrimination was assessed using an AXB discrimination task in quiet and using the Quick Speech in Noise (QuickSIN) test. SE bilinguals were outperformed by AE and AE-SNHL monolinguals, suggesting SE bilinguals primarily use their L1 acoustic properties to discriminate speech segments. No significant difference was found in QuickSIN performance between the bilingual and the monolingual groups, but there was a significant difference between AE and AE-SNHL. In conclusion, vowel discrimination was affected by interference with the native language, while performance in the noise condition was affected by hearing loss. The results of this study contribute to our understanding of the age-related speech processing deficits from three different aging groups regarding the cognitive control system.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"4 ","pages":"1302050"},"PeriodicalIF":3.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565406","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}