Frontiers in aging最新文献

{"title":"From bench to bedside: translational insights into aging research.","authors":"Kanti Bhooshan Pandey","doi":"10.3389/fragi.2025.1492099","DOIUrl":"10.3389/fragi.2025.1492099","url":null,"abstract":"<p><p>Aging research has rapidly advanced from fundamental discoveries at the molecular and cellular levels to promising clinical applications. This review discusses the critical translational insights that bridge the gap between bench research and bedside applications, highlighting key discoveries in the mechanisms of aging, biomarkers, and therapeutic interventions. It underscores the importance of interdisciplinary approaches and collaboration among scientists, clinicians, and policymakers to address the complexities of aging and improve health span.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"6 ","pages":"1492099"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384325","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":"The research progress of biologics in elderly-onset rheumatoid arthritis (EORA).","authors":"Yujie Li, Yifan Liu, Yanhui Tian, Huimin Gu, Qingliang Meng, Jiakang Cui, Junfu Ma","doi":"10.3389/fragi.2024.1511812","DOIUrl":"10.3389/fragi.2024.1511812","url":null,"abstract":"<p><p><i>Elderly-onset rheumatoid arthritis (EORA)</i> is a distinct subtype of <i>rheumatoid arthritis</i> characterized by heightened treatment challenges due to immune aging and the complexity of comorbidities. This review systematically summarizes the definition, clinical features, epidemiological trends, therapeutic challenges, and the potential applications of biologic agents in <i>EORA</i>. It primarily focuses on the efficacy, safety, and individualized treatment strategies associated with various biologic agents. Studies indicate that biologics, such as <i>TNF-</i>α <i>inhibitors</i>, <i>IL-6 inhibitors</i>, and <i>JAK inhibitors</i>, can significantly reduce inflammation and improve joint function in <i>EORA</i> patients. However, their long-term use is closely linked to increased risks of infections, thrombosis, and malignancies, underscoring the importance of personalized treatment approaches and dynamic monitoring. Moreover, the advent of novel biologic agents, including <i>IL-17</i> and <i>IL-23 inhibitors</i>, as well as second-generation <i>JAK inhibitors</i>, offers additional therapeutic options for refractory patients and demonstrates substantial potential in optimizing both efficacy and safety. With the rapid progress of precision medicine and artificial intelligence (AI) technologies, gene profiling, biomarker analysis, and AI-assisted decision-making are gradually steering <i>EORA</i> treatment towards more personalized and precise strategies. However, the high cost of treatment and the limited accessibility of these technologies remain significant barriers in clinical practice. Future research should focus on validating the long-term safety of novel therapies and refining individualized treatment strategies to enhance patient outcomes and quality of life.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1511812"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366858","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":"Markers of immunosenescence in CMV seropositive healthy elderly adults.","authors":"Ivón Johanna Rodríguez, Carlos Alberto Parra-López","doi":"10.3389/fragi.2024.1436346","DOIUrl":"10.3389/fragi.2024.1436346","url":null,"abstract":"<p><p>A significant increase in life expectancy has accompanied the growth of the world's population. Approximately 10% of the global population are adults over 60, and it is estimated that 2050 this figure will double. This increase in the proportion of older adults leads to a more significant burden of age-related diseases. Immunosenescence predisposes elderly individuals to a higher incidence of infectious and chronic non-communicable diseases with higher mortality rates. Despite advances in research, it is necessary to evaluate the cellular characteristics of the aging immune system in populations with a high incidence of latent viruses such as cytomegalovirus (CMV). In this sense, this work aimed to identify senescence markers in cells of the innate and adaptive immune system in healthy older adults with CMV infection. We observed that older adults present an increase in the population of CD14⁺CD16⁺ intermediate monocytes, an expansion of CD56neg NK cells with an increase in the expression of CD57, as well as a decrease in the naïve CD4⁺ and CD8⁺ T cells, accompanied by an increased expression of senescence markers CD57 and KLRG1 in effector CD8⁺ T cells.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1436346"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366856","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":"Precise and interpretable neural networks reveal epigenetic signatures of aging across youth in health and disease.","authors":"David Martínez-Enguita, Thomas Hillerton, Julia Åkesson, Daniel Kling, Maria Lerm, Mika Gustafsson","doi":"10.3389/fragi.2024.1526146","DOIUrl":"10.3389/fragi.2024.1526146","url":null,"abstract":"<p><strong>Introduction: </strong>DNA methylation (DNAm) age clocks are powerful tools for measuring biological age, providing insights into aging risks and outcomes beyond chronological age. While traditional models are effective, their interpretability is limited by their dependence on small and potentially stochastic sets of CpG sites. Here, we propose that the reliability of DNAm age clocks should stem from their capacity to detect comprehensive and targeted aging signatures.</p><p><strong>Methods: </strong>We compiled publicly available DNAm whole-blood samples (n = 17,726) comprising the entire human lifespan (0-112 years). We used a pre-trained network-coherent autoencoder (NCAE) to compress DNAm data into embeddings, with which we trained interpretable neural network epigenetic clocks. We then retrieved their age-specific epigenetic signatures of aging and examined their functional enrichments in age-associated biological processes.</p><p><strong>Results: </strong>We introduce NCAE-CombClock, a novel highly precise (R² = 0.978, mean absolute error = 1.96 years) deep neural network age clock integrating data-driven DNAm embeddings and established CpG age markers. Additionally, we developed a suite of interpretable NCAE-Age neural network classifiers tailored for adolescence and young adulthood. These clocks can accurately classify individuals at critical developmental ages in youth (AUROC = 0.953, 0.972, and 0.927, for 15, 18, and 21 years) and capture fine-grained, single-year DNAm signatures of aging that are enriched in biological processes associated with anatomic and neuronal development, immunoregulation, and metabolism. We showcased the practical applicability of this approach by identifying candidate mechanisms underlying the altered pace of aging observed in pediatric Crohn's disease.</p><p><strong>Discussion: </strong>In this study, we present a deep neural network epigenetic clock, named NCAE-CombClock, that improves age prediction accuracy in large datasets, and a suite of explainable neural network clocks for robust age classification across youth. Our models offer broad applications in personalized medicine and aging research, providing a valuable resource for interpreting aging trajectories in health and disease.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1526146"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366857","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":"Analyzing the cancer mortality-to-incidence ratios and health expenditures in the aging population: a 20-year comparative study across high-income countries.","authors":"Majed Ramadan, Shadell AlGhamdi, Rawiah Alsiary","doi":"10.3389/fragi.2025.1506897","DOIUrl":"10.3389/fragi.2025.1506897","url":null,"abstract":"<p><strong>Background: </strong>The global burden of cancer is expected to increase by 60% over the next two decades, largely due to population aging. The study aims to examine the association between cancer mortality-to-incidence ratios (MIR) with healthcare expenditures (HE), and human development index score for individuals 70 years old or older.</p><p><strong>Method: </strong>This is an epidemiological study using publicly available data from the Global Burden of Disease (GBD) for six over the years 1990-2019. A generalized linear model was employed to examine the association between MIR, and health expenditures and health development index score.</p><p><strong>Results: </strong>Included countries showed a statistically significant negative association between MIR and both HE, and HE, indicating that higher HDI and HE are associated with decreased MIR with the highest decrease was for China, the coefficient for HDI is -1.29 (95% CI: -1.35 to -1.24, p < 0.0001), the coefficient for HE is -0.103 (95% CI: -0.17 to -0.03, p < 0.0001). There are variations exist in MIRs between high and low health expenditure countries for each cancer type.</p><p><strong>Conclusion: </strong>The study reveals a significant impact of HE and HDI on cancer outcomes in older adults. Variations between high and low HE nations highlight potentially improved cancer outcomes in high HE countries. Considering the anticipated growth in the aging population worldwide, a rise in cancer cases is expected among older individuals. The implications are profound, suggesting an impending strain on healthcare systems, particularly in nations with a high proportion of elderly and low health expenditures.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"6 ","pages":"1506897"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366859","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":"Hallmarks of aging: middle-aging hypovascularity, tissue perfusion and nitric oxide perspective on healthspan.","authors":"Teow J Phua","doi":"10.3389/fragi.2024.1526230","DOIUrl":"10.3389/fragi.2024.1526230","url":null,"abstract":"<p><p>Aging is a complex process marked by various changes at both cellular and systemic levels, impacting the functioning and lifespan of organisms. Over time, researchers have pinpointed several significant hallmarks of aging that lead to the gradual deterioration of tissue function, regulation, and homeostasis associated with aging in humans. Despite this, the intricate interactions and cumulative effects of these hallmarks are still mostly uncharted territory. Understanding this complex web is a major challenge in Geroscience, yet it is crucial for developing effective strategies that promote healthy aging, reduce medical costs, and ensure the sustainability of health systems. Gaining insights in this area is essential for creating interventions that can slow the aging process, enhance healthspan, and decrease the likelihood of age-related diseases. The integration of knowledge from various fields concerning the middle-aging nitric oxide (NO)-mediated hypovascularity hypoxia hemodynamic hypothesis points to a systems-based approach to the biological hallmarks of aging. Key evidence suggests a systemic connection between the endocrine system (specifically sex hormones), endogenous NO deficiency, and the vascular system, which serves as a network of microvascular structures crucial for tissue perfusion functions at cellular level. These processes also involve oxidative stress and inflammation triggered by hypoxia.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1526230"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017433","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":"Age-associated alterations in immune and inflammatory responses in captive olive baboons (<i>Papio anubis</i>).","authors":"Michele M Mulholland, Bharti P Nehete, Ashley DeLise, Angela M Achorn, Lisa M Pytka, Pramod N Nehete","doi":"10.3389/fragi.2024.1511370","DOIUrl":"10.3389/fragi.2024.1511370","url":null,"abstract":"<p><strong>Introduction: </strong>Advanced age is a primary risk factor for many chronic diseases and conditions; however, age-related immune dysregulation is not well understood. Animal models, particularly those that resemble human age-related physiological changes, are needed to better understand immunosenescence and to improve health outcomes. Here, we explore the utility of the olive baboon (Papio anubis) in studying age-related changes to the immune system and understanding mechanisms of immunosenescence.</p><p><strong>Methods: </strong>We examined immune cell, inflammatory responses, cytokines, and cortisol levels using hematology and flow cytometry, mitogen stimulation, multiplex cytokine assay, and cortisol immunoassay.</p><p><strong>Results and discussion: </strong>Our results reveal significant age effects on numerous immune and inflammatory responses. For instance, adult and aged monkeys exhibited significantly fewer monocytes than young monkeys. After stimulation with Con A and PWM (separately), we found that old baboons had higher INFγ expression compared to young baboons. Similarly, after stimulation with LPS and PWM (separately), we found that old baboons had higher TNFα expression compared to young baboons. These findings suggest that the olive baboon is a suitable model for biogerontology research, immune senescence, and development of vaccines. Though there are phenotypic and functional similarities between baboons and humans, specific differences exist in immune cell expression and immune function of lymphocytes that should be considered for better experimental outcomes in the development of therapeutics and restoring innate and adaptive immune function in aged individuals.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1511370"},"PeriodicalIF":3.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017428","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":"DNA methylation, histone acetylation in the regulation of memory and its modulation during aging.","authors":"Padmanabh Singh, Vijay Paramanik","doi":"10.3389/fragi.2024.1480932","DOIUrl":"10.3389/fragi.2024.1480932","url":null,"abstract":"<p><p>Memory formation is associated with constant modifications of neuronal networks and synaptic plasticity gene expression in response to different environmental stimuli and experiences. Dysregulation of synaptic plasticity gene expression affects memory during aging and neurodegenerative diseases. Covalent modifications such as methylation on DNA and acetylation on histones regulate the transcription of synaptic plasticity genes. Changes in these epigenetic marks correlated with alteration of synaptic plasticity gene expression and memory formation during aging. These epigenetic modifications, in turn, are regulated by physiology and metabolism. Steroid hormone estrogen and metabolites such as S-adenosyl methionine and acetyl CoA directly impact DNA and histones' methylation and acetylation levels. Thus, the decline of estrogen levels or imbalance of these metabolites affects gene expression and underlying brain functions. In the present review, we discussed the importance of DNA methylation and histone acetylation on chromatin modifications, regulation of synaptic plasticity gene expression and memory consolidation, and modulation of these epigenetic marks by epigenetic modifiers such as phytochemicals and vitamins. Further, understanding the molecular mechanisms that modulate these epigenetic modifications will help develop recovery approaches.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1480932"},"PeriodicalIF":3.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017431","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":"The aldose reductase inhibitors AT-001, AT-003 and AT-007 attenuate human keratinocyte senescence.","authors":"Gautham Yepuri, Kushie Kancharla, Riccardo Perfetti, Shoshana Shendelman, Andrew Wasmuth, Ravichandran Ramasamy","doi":"10.3389/fragi.2024.1466281","DOIUrl":"10.3389/fragi.2024.1466281","url":null,"abstract":"<p><p>Human skin plays an important role protecting the body from both extrinsic and intrinsic factors. Skin aging at cellular level, which is a consequence of accumulation of irreparable senescent keratinocytes is associated with chronological aging. However, cell senescence may occur independent of chronological aging and it may be accelerated by various pathological conditions. Recent studies have shown that oxidative stress driven keratinocyte senescence is linked to the rate limiting polyol pathway enzyme aldose reductase (AR). Here we investigated the role of three novel synthetic AR inhibitors (ARIs) AT-001, AT-003 and AT-007 in attenuating induced skin cell senescence, in primary normal human keratinocytes (NHK cells), using three different senescence inducing agents: high glucose (HG), hydrogen peroxide (H₂O₂) and mitomycin-c (MMC). To understand the efficacy of ARIs in reducing senescence, we have assessed markers of senescence, including SA-β-galactosidase activity, γ-H2AX foci, gene expression of <i>CDKN1A, TP53</i> and <i>SERPINE1</i>, reactive oxygen species generation and senescence associated secretory phenotypes (SASP). Strikingly, all three ARIs significantly inhibited the assessed senescent markers, after senescence induction. Our data confirms the potential role of ARIs in reducing NHK cell senescence and paves the way for preclinical and clinical testing of these ARIs in attenuating cell aging and aging associated diseases.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1466281"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916478","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":"New insights into methods to measure biological age: a literature review.","authors":"Aanchal Mathur, Sebastien Taurin, Sfoug Alshammary","doi":"10.3389/fragi.2024.1395649","DOIUrl":"10.3389/fragi.2024.1395649","url":null,"abstract":"<p><p>Biological age is a concept that reflects the physiological state of an individual rather than the chronological time since birth. It can help assess the risk of age-related diseases and mortality and the effects of interventions to slow down or reverse aging. However, there is no consensus on measuring biological age best, and different methods may yield different results. In this paper, which includes 140 relevant pieces of literature, out of 33,000, we review some new methods to measure biological age based on recent advances in biotechnology and data science. We discussed some novel biomarkers and algorithms that can capture the dynamic and multidimensional aspects of aging at different levels. We evaluate their performance and validity using various datasets and criteria and compare them with existing methods. We also discuss their potential applications and implications for aging research and clinical practice. We conclude that the new methods offer more accurate and reliable estimates of biological age and open new avenues for understanding and modulating the aging process.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1395649"},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916470","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}