Aging and Disease最新文献

{"title":"Anti-Müllerian Hormone Concentrations in Women of Different Reproductive Age and the Chances of IVF Outcome: A Paradigm Shift is needed.","authors":"Jakub Wyroba, Joanna Kochan, Liam Kelley, Sharif Iqbal, Paweł Kordowitzki","doi":"10.14336/AD.2024.1615","DOIUrl":"https://doi.org/10.14336/AD.2024.1615","url":null,"abstract":"<p><p>The study of Anti-Müllerian Hormone (AMH) has garnered considerable attention due to its critical implications in assessing and understanding both female and male fertility potential. Traditionally, AMH is recognized for its pivotal role in evaluating ovarian reserve and is a cornerstone in reproductive health assessments for women. The aim of this study was to challenge the traditional interpretation of AMH as a standalone predictor of IVF success. Through a retrospective analysis of 600 patients undergoing ICSI, we reveal that women with low AMH levels, traditionally classified as poor responders, can achieve unexpectedly high oocyte numbers, blastocyst formation, and pregnancy rates. This highlights the limitations of using AMH alone to predict IVF outcomes. Our findings advocate the importance of integrating additional factors, such as follicle-stimulating hormone (FSH), and the need for a more individualized approach to fertility treatment planning.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting the Fractionation of Stable Isotopes in Biochemical Processes for Medical Diagnosis: A Narrative Review.","authors":"Markus A Hobert, Niklas Helle, Christopher Siebert, Anton Eisenhauer, Martha Gledhill, Walter Maetzler","doi":"10.14336/AD.2024.1577","DOIUrl":"https://doi.org/10.14336/AD.2024.1577","url":null,"abstract":"<p><p>Analysis of isotope distributions plays a crucial role in medical diagnostics. While radioactive and radiogenic isotopes - those that undergo or result from radioactive decay - are widely used, stable isotopes are less commonly applied despite their significant diagnostic potential. For example, calcium isotope ratio analysis is already commercially utilized for calcium loss and the early diagnosis of osteoporosis. Additionally, analyses of iron, copper, and zinc isotope ratios have been explored in various conditions, including hemochromatosis, Wilson's disease, cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. Altered isotope ratios in these diseases are thought to reflect pathophysiologically relevant processes, making them promising biomarkers. This review provides a comprehensive overview of the current and potential applications of stable isotope analysis in medicine.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Role of Mitochondrial DNA Mutations in Aging: Bridging Theoretical Expectations with Empirical Observations.","authors":"Runyu Liang, Qiang Tang, Jia Chen, Yongyin Huang, Luwen Zhu","doi":"10.14336/AD.2024.1469","DOIUrl":"https://doi.org/10.14336/AD.2024.1469","url":null,"abstract":"<p><p>Since the association between mitochondria and aging was first identified, significant efforts have been devoted to elucidating the role of mitochondrial DNA mutations in the aging process. Due to their age-dependent accumulation, intrinsically high mutation rates, and defective replication mechanisms, mtDNA mutations have often been regarded as pivotal drivers of aging. This has led to certain intuitive yet inherently limited conclusions. Aging, however, is a multifactorial process, and the role of mtDNA cannot be simply categorized in binary terms, as its influence emerges as a composite vector of numerous interconnected physiological processes. Adopting alternative perspectives may mitigate the discrepancies between theoretical expectations and empirical findings, offering new directions and insights for future research.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental Alcohol Use Disrupts Offspring Mitochondrial Activity, Promoting Susceptibility to Toxicant-Induced Liver Cancer.","authors":"Alison Basel, Sanat S Bhadsavle, Katherine Z Scaturro, Grace K Parkey, Yava Jones-Hall, Michael C Golding","doi":"10.14336/AD.2024.1372","DOIUrl":"10.14336/AD.2024.1372","url":null,"abstract":"<p><p>The early onset and incidence of liver disease and hepatocellular carcinoma have doubled in the last two decades and are primarily attributed to an unhealthy lifestyle. However, emerging studies suggest that increases in these age-related pathologies may link to heritable alterations in the control of cellular bioenergetics induced by the parental environment. Because our preclinical studies examining the fetal offspring of alcohol-exposed males and females have consistently identified epigenetic alterations in mitochondrial activity, we hypothesized that chronic parental alcohol exposure programs an increased predisposition of offspring to develop liver disease and hepatocellular carcinoma induced by an environmental toxicant. Here, we employed a multiplex mouse model to compare the sensitivities of male offspring derived from maternal, paternal, and dual-parental alcohol exposures to the potent hepatocellular carcinoma inducer Diethylnitrosamine and determine their predisposition for tumor formation and growth. Our analysis reveals that parental alcohol exposures disrupt the activity of offspring mitochondrial complex I in the liver, promoting enduring oxidative stress and activating Transforming Growth Factor β signaling. This lasting imbalance correlates with increased Interleukin 6 production, promoting an inflammatory precancerous state. In male offspring, chronic parental alcohol consumption leads to increased tumor incidence, multiplicity, and size. Significantly, maternal and paternal alcohol use interact in driving the progression of toxicant-induced liver disease, with some adverse outcomes of dual-parental offspring exceeding those caused by either maternal or paternal alcohol use alone. We conclude that chronic parental alcohol use alters mitochondrial complex I activity and immune function, predisposing male offspring to a proinflammatory precancerous state.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Chondrogenic Potential and Osteoarthritis Treatment Using Cyaonoside A-Induced MSC Delivered via a Hyaluronic Acid-Based Hydrogel System.","authors":"Xingyan An, Qirong Zhou, Shihao Sheng, Anfu Deng, Han Liu, Xiuhui Wang, Qin Zhang, Yingying Jing, Ke Xu, Chongru He, Robert Chunhua Zhao, Jiacan Su","doi":"10.14336/AD.2024.10016","DOIUrl":"https://doi.org/10.14336/AD.2024.10016","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts the quality of life in the elderly. Traditional Chinese medicine, particularly Medicinal Cyathula Root and its active component Cyaonoside A (CyA), has been utilized to treat OA by promoting chondrocyte proliferation, inhibiting inflammatory factors, and maintaining joint homeostasis. Concurrently, mesenchymal stem cells (MSC) derived from placental umbilical cord, bone marrow, and adipose tissue have gained attention for their potential in OA treatment due to their chondrogenic differentiation capabilities. This study explored the therapeutic synergy of CyA and MSC for enhanced cartilage regeneration. Optimal chondrogenic differentiation was achieved by treating MSC with 0.5 mg/mL CyA for 3 days, significantly increasing the expression of key cartilage-specific genes ACAN, COL2A, and SOX9. Comparative gene expression and pathway analyses revealed that CyA-induced MSC (C-MSC) modulate critical signaling pathways, including TGF-β, PI3K-Akt, and Wnt, demonstrating their potential in cartilage repair. Furthermore, C-MSC-derived exosomes exhibited superior anti-inflammatory and anti-apoptotic effects compared to MSC-derived exosomes in IL-1β-treated human chondrocytes, enhancing chondrogenic gene expression and reducing cartilage degradation. To enable targeted delivery, a novel injectable hydrogel system (HAMA@C-MSC) was developed using methylacrylated hyaluronic acid (HAMA). This hydrogel facilitated uniform cell distribution, maintained structural integrity, and demonstrated excellent biocompatibility and biosafety, with no cytotoxic or hemolytic effects. In vivo studies using a rat destabilization of the medial meniscus OA model confirmed that HAMA@C-MSC significantly improved cartilage structure, enhanced chondrocyte regeneration, and restored collagen integrity, outperforming other treatment groups as validated through imaging, histology, and molecular analyses. These findings highlight HAMA@C-MSC as a promising therapeutic strategy for OA, leveraging the synergistic effects of C-MSC and advanced hydrogel technology to achieve enhanced cartilage regeneration and joint protection.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Lipid Droplet Transport Dynamics as Biomarkers of Senescence Using Label-Free, Time-Lapse Holotomography.","authors":"Amarnath Singam, Nikita Gopakumar, Apoorva Chauhan, Kimberly Ramirez, Jeong Hee Kim, Chandrabali Bhattacharya, Jingchun Chen, Deok-Ho Kim, Seungman Park","doi":"10.14336/AD.2024.1408","DOIUrl":"https://doi.org/10.14336/AD.2024.1408","url":null,"abstract":"<p><p>Accumulation and density of lipid droplets (LDs) in cells have been identified as a potential biomarker to detect senescent cells. However, their intracellular dynamic transport and alterations during senescence remain largely unclear. To address this knowledge gap, senescence was induced in human microglia cells using hydrogen peroxide (H₂O₂) to investigate both short-term and long-term effects of H₂O₂ treatment on LD dynamics. We captured time-lapse holotomograms of LDs using label-free refractive index (RI)-based holotomography and quantified 11 dynamic parameters of LDs through single-particle tracking. These quantified parameters were then compared across healthy cells, short-term H₂O₂-treated pre-senescent cells (H₂O₂-treated cells), and long-term H₂O₂-induced senescent cells (senescent cells). The results revealed that LD dynamics are significantly altered in both H₂O₂-treated pre-senescent cells and H₂O₂-induced senescent cells, though with differing trends. Healthy cells exhibited higher values in all LD dynamic parameters compared to senescent cells, with the exception of the mean directional change rate, which is lower. In addition, H₂O₂-treated cells showed higher values in dynamic parameters such as total displacement, mean straight-line velocity, and confinement ratio compared to healthy and senescent cells, due to the observed linear migration of LDs during H₂O₂ treatment. We found that the altered movement of LDs is closely related to H₂O₂-induced damage to microtubule networks. These findings suggest that altered LD dynamics, along with associated molecules and pathways, may serve as potential biomarkers for identifying senescent cells, thereby aiding in the development of novel therapeutic targets and senolytics.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Connection Between the Gut Microbiome and Epigenetic Modification in Age-Related Cancer: A Narrative Review.","authors":"Florida Owens, Joseph Souchak, Valeria Nazaire, Juliet Akkaoui, Rajib Shil, Candy Carbajal, Kingshuk Panda, David Caraballo Delgado, Inge Claassen, Santiago Moreno, Samantha Yi, Yishu Dong, Nirbachita Adrita, Lee-Seng Lau, Nazira El-Hage","doi":"10.14336/AD.2024.1618","DOIUrl":"https://doi.org/10.14336/AD.2024.1618","url":null,"abstract":"<p><p>As individuals age, physiological changes influence the composition and function of the gut microbiome, significantly impacting the onset and progression of various illnesses, including cancer. Notably, the gut microbiome affects epigenetic modifications such as DNA methylation and histone alterations. Furthermore, it contributes to the age-related decline in immune system efficiency, increasing susceptibility to infections and cancers. This dual role of the gut microbiome-both a protective factor and a risk factor-is a key aspect of its importance in maintaining long-term health, making it a significant topic of discussion in this review. Moreover, a challenge faced by the elderly is the concurrent use of multiple medications. Polypharmacy can interact with the gut microbiome, potentially altering its efficacy, leading to adverse drug reactions, and affecting vital microbiome diversity. The effects of these interactions on cancer therapies and the overall health of elderly patients are becoming increasingly important. Understanding the complex relationship between aging, the gut microbiome, cancer, and polypharmacy is crucial for developing more effective therapeutic strategies and improving patient outcomes. Here, we discuss recent advances in understanding age-related physiological changes in the microbiome and their significance in cancer development and therapy. Specifically, we will explor how epigenetic changes acquired during aging, along with ongoing prescriptions of multiple medications and the decline of immune function, contribute to the intricate relationship between aging and cancer.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Associated Activation of the cGAS-STING Pathway and Impairment of DNA Damage Repair in Human Primary Alveolar Type II Cells.","authors":"Chih-Ru Lin, Hassan Hayek, Hannah Simborio, Loukmane Karim, Karim Bahmed, Sudhir Bolla, Nathaniel Marchetti, Gerard J Criner, Ying Tian, Beata Kosmider","doi":"10.14336/AD.2024.1175","DOIUrl":"https://doi.org/10.14336/AD.2024.1175","url":null,"abstract":"<p><p>Homeostatic imbalance and lung function decline are central physiological characteristics of aging and susceptibility to respiratory diseases. Senescence contributes to tissue damage and alveolar epithelial cell injury and decreases reparative capacity. Alveolar type II (ATII) cells have stem cell potential and self-renew to regenerate the alveoli after damage. They were isolated from younger and older non-smoker and smoker organ donors to define their function in the lung. Smoking and older age increased ATII cell senescence as detected by high β-galactosidase activity and P21 levels by Western blotting and RT-PCR. Also, the number of ATII cells was the lowest in lung tissue in older smokers. This was associated with increased stress signaling, as shown by elevated 4-HNE and G3BP1 expression in ATII cells, and inflammation indicated by high IL-8 levels in BAL fluid. In addition, DNA damage and decreased repair were observed using the comet assay, especially in ATII cells isolated from older smokers. This was accompanied by the highest levels of cytosolic double-strand DNA in this group and correlated with the activated cGAS-STING pathway and increased IRF3 expression. Moreover, telomere shortening, accumulation of TERRA molecules, and increased ZBP1 protein expression in ATII cells were associated with smoking and older age. Reduced NRF2 and DJ-1 expression in ATII cells was detected by Western blotting, especially in older smokers, which suggests an antioxidant defense system dysfunction. Our study provides insights into the impaired interconnected signaling network, which can contribute to ATII cell senescence.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Promotes Axonal Atrophy through Alterations in Microtubules and EB1 Function.","authors":"Samuel Shields, Emilia Gregory, Oliver Wilkes, IIlana Gozes, Natalia Sanchez-Soriano","doi":"10.14336/AD.2024.0839","DOIUrl":"https://doi.org/10.14336/AD.2024.0839","url":null,"abstract":"<p><p>Axons are crucial for transmitting neurochemical signals. As organisms age, the ability of neurons to maintain their axons declines; hence, aged axons are more susceptible to damage or dysfunction. Understanding how aging causes axonal vulnerability is crucial for developing strategies to enhance overall resilience of neurons and prevent neuronal deterioration during aging and in age-related neurodegenerative diseases. Increasing levels of reactive oxygen species (ROS) causes oxidative stress - a hallmark of aging and age-related diseases. Despite this association, a causal relationship between oxidative stress and neuronal aging remains unclear, particularly in how subcellular physiology may be affected by ROS. By using Drosophila-derived primary neuronal cultures and a recently developed in vivo neuronal model of aging, which involves the visualisation of Drosophila medulla neurons, we investigated the interplay between oxidative stress, neuronal aging and the microtubule cytoskeleton. Our results showed that oxidative stress is a key driver of axonal and synaptic decay, as shown by an enhanced appearance of axonal swellings, microtubule alterations (in both axons and synapses) and morphological transformation of axonal terminals during aging. We demonstrated that increasing the levels of ROS sensitises microtubule plus end-binding protein 1 (EB1), leading to microtubule defects that effect neuronal integrity. Furthermore, manipulating EB1 proved to be a valuable therapeutic strategy to prevent aging hallmarks enhanced in conditions of elevated ROS. In summary, we demonstrate a mechanistic pathway linking cellular oxidative stress with changes in the microtubule cytoskeleton leading to axonal deterioration during aging and provide evidence of the therapeutic potential of enhancing microtubule plus-end physiology to improve the resilience of axons.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Hydrocephalus Management: Pathogenesis Insights, Therapeutic Innovations, and Emerging Challenges.","authors":"Xiuyun Liu, Hui Zhi, Marek Czosnyka, Chiara Robba, Zofia Czosnyka, Jennifer Lee Summers, Huijie Yu, Xiaoguang Tong, Guoyi Gao, Gelei Xiao, Kai Yu, Yan Xing, Renling Mao, Shaoya Yin, Yangong Chao, Hongliang Li, Ke Pu, Keke Feng, Meijun Pang, Dong Ming","doi":"10.14336/AD.2024.1434","DOIUrl":"https://doi.org/10.14336/AD.2024.1434","url":null,"abstract":"<p><p>Hydrocephalus is a prevalent neurological disorder, particularly impactful in older adults, characterized by high incidence and numerous complications that impose a significant burden on healthcare systems. This review aims to provide a comprehensive description of hydrocephalus pathogenesis, focusing on cellular and molecular insights derived from animal models. We also present the latest advances in hydrocephalus research and highlight potential therapeutic targets. Lastly, the review advocates the integration of findings from both animal and human studies to achieve better outcomes and examines the potential of emerging technologies. We wish to raise public attention about this disease in an aging society. Current animal models for hydrocephalus involve acquired hydrocephalus models and genetic/congenital hydrocephalus models. Studies from animals have shown that the main mechanisms of models can be broadly classified into nine types. A variety of drug-targeted therapy methods and non-surgical treatment methods have been used in clinical practice. But current treatment approaches primarily focus on symptomatic relief and intracranial pressure control rather than addressing the underlying pathological mechanisms. We call for the development of more accurate and representative animal models to achieve better outcomes and examine the potential of emerging technologies, such as artificial intelligence and neuroimaging. In summary, this review synthesizes recent findings in hydrocephalus research, identifies promising therapeutic targets and interventions, and critically evaluates the limitations of current research paradigms, aiming to align preclinical studies with clinical endpoints. Continued studies and multidisciplinary collaboration are essential to develop effective interventions and facilitate new treatments into bedside.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}