{"title":"Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body.","authors":"Xingyu Liu, Yuanqu Zhao, Yanzhi Feng, Shixuan Wang, Aiyue Luo, Jinjin Zhang","doi":"10.14336/AD.2024.1468","DOIUrl":"https://doi.org/10.14336/AD.2024.1468","url":null,"abstract":"<p><p>Age-related diseases have emerged as a global concern as the population ages. Consequently, understanding the underlying causes of aging and exploring potential anti-aging interventions is imperative. In females, the ovaries serve as the principal organs responsible for ovulation and the production of female hormones. The aging ovaries are related to infertility, menopause, and associated menopausal syndromes, with menopause representing the culmination of ovarian aging. Current evidence indicates that ovarian aging may contribute to dysfunction across multiple organ systems, including, but not limited to, cognitive impairment, osteoporosis, and cardiovascular disease. Nevertheless, due to the widespread distribution of sex hormone receptors throughout the body, ovarian aging affects not only these specific organs but also influences a broader spectrum of age-related diseases in women. Despite this, the impact of ovarian aging on overall age-related diseases has been largely neglected. This review provides a thorough summary of the impact of ovarian aging on age-related diseases, encompassing the nervous, circulatory, locomotor, urinary, digestive, respiratory, and endocrine systems. Additionally, we have outlined prospective therapeutic approaches for addressing both ovarian aging and age-related diseases, with the aim of mitigating their impacts and preserving women's fertility, physical health, and psychological well-being.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447752","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":"Capsaicin and TRPV1: A Novel Therapeutic Approach to Mitigate Vascular Aging.","authors":"Xing-Yu Cui, Jun-Kun Zhan","doi":"10.14336/AD.2024.1292","DOIUrl":"https://doi.org/10.14336/AD.2024.1292","url":null,"abstract":"<p><p>Vascular aging and its associated diseases represent a principal cause of mortality among the global elderly population, making the mitigation of vascular aging a significant aspiration for humanity. This article explores the intersection of nature and health, focusing on the role of the natural plant, pepper, and its principal bioactive compound, capsaicin, in combating vascular aging. By examining molecular and cellular mechanisms as well as phenotypic alterations in blood vessels, we offer a comprehensive review of the effects of capsaicin and its receptor, transient receptor potential vanilloid 1 (TRPV1), within vascular aging. We propose that capsaicin may serve as the medication with the potential to slow the progress of vascular aging and could constitute a new strategy to treat vascular aging related disease.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447747","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}
Eliska Vacurova, Edita Vlachova, Jan Stursa, Klara Bohacova, Tereza Havrlantova, Vojtech Skop, Barbora Judita Kasperova, Lukas Werner, Jiri Neuzil, Martin Haluzik, Sona Stemberkova Hubackova
{"title":"Targeting Mitochondrial Integrity as a New Senolytic Strategy.","authors":"Eliska Vacurova, Edita Vlachova, Jan Stursa, Klara Bohacova, Tereza Havrlantova, Vojtech Skop, Barbora Judita Kasperova, Lukas Werner, Jiri Neuzil, Martin Haluzik, Sona Stemberkova Hubackova","doi":"10.14336/AD.2024.1100","DOIUrl":"https://doi.org/10.14336/AD.2024.1100","url":null,"abstract":"<p><p>Aging, characterized by accumulation of senescent cells, is a driving factor of various age-related diseases. These conditions pose significant health risks globally due to their increasing prevalence and serious complications. Reduction of senescent cells therefore represents a promising strategy promoting healthy aging. Here we demonstrate that targeting tamoxifen to mitochondria via triphenyl and tricyclohexyl phosphine selectively eliminates senescent cells. Our findings show a complex effect of mitochondrially targeted tamoxifen on mitochondrial function and integrity of senescent cells, including inhibition of oxidative phosphorylation and activity of respiratory complex IV. These changes result in activation of ferroptosis as the major mode of cell death, which results in rejuvenation of tissues. Targeting mitochondria of senescent cells represents a general senolytic strategy and may extend the healthspan and improve the quality of life in aging populations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447701","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}
Sujung Oh, Hee-Young Sohn, Junwoo Seo, Eunjee Kang, Jae Kyung Park, So Young Moon, Hee Jin Kim, Na-Yeon Jung, Sun Min Lee, Bo Kyoung Cheon, Hyemin Jang, Sung Hoon Kang, Sarang Kang, Kyu Yeong Choi, Sang-Won Yoo, Yun Joong Kim, Juhee Cho, Eun-Joo Kim, Sang Won Seo, Kun Ho Lee, Joong-Seok Kim, Young Ho Koh, Chi-Hun Kim, Munjin Kwon, Danbee Kang
{"title":"Profile for Brain Disease Research Infrastructure for Data Gathering and Exploration (BRIDGE) Platform.","authors":"Sujung Oh, Hee-Young Sohn, Junwoo Seo, Eunjee Kang, Jae Kyung Park, So Young Moon, Hee Jin Kim, Na-Yeon Jung, Sun Min Lee, Bo Kyoung Cheon, Hyemin Jang, Sung Hoon Kang, Sarang Kang, Kyu Yeong Choi, Sang-Won Yoo, Yun Joong Kim, Juhee Cho, Eun-Joo Kim, Sang Won Seo, Kun Ho Lee, Joong-Seok Kim, Young Ho Koh, Chi-Hun Kim, Munjin Kwon, Danbee Kang","doi":"10.14336/AD.2024.1432","DOIUrl":"https://doi.org/10.14336/AD.2024.1432","url":null,"abstract":"<p><p>Brain diseases complexity have necessitated advanced research platforms for better understanding, treatment, and prevention strategies. However, existing brain disease registries face limitations such as incomplete variable sets, lack of standardization, insufficient linkage to external databases, absence of integrated platforms for comprehensive data collection, and lack of continuity. To address these challenges, the Korea National Institute of Health initiated the Brain disease Research Infrastructure for Data Gathering and Exploration (BRIDGE), a national prospective platform designed to overcome the shortcomings of current registries. The BRIDGE platform includes a Longitudinal Study of Early onset dementia And Family members (LEAF) cohort, a Longitudinal/cohort Study of Patients with Late Onset Dementia (LLOD) cohort, a community-based cohort study of High-risk individuals for Dementia (COHD) cohort, and a Longitudinal Study of Patients with Parkinson's Disease (LoPD) cohort. The standardized variables included sociodemographic variables, health behaviors, medical history, activities of daily living, behavioral, and psychological problems, cognitive function, disease-related symptoms, quality of life (QoL), sleep, depression scale, caregiver burden, physical health, blood tests, olfactory function testing, orthostatic blood pressure changes, genetic testing, nerve conduction studies, and neuroimaging. In addition, the BRIDGE platform will be linked to the Korean National Health Insurance Service (K-NHIS) database. By addressing gaps in data collection, standardization, and considering a wide range of impacts, the BRIDGE database offers new pathways for understanding and combating complex brain conditions. As the project progresses, it has the potential to significantly influence scientific understanding and policymaking in the field of brain health.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447700","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}
Sharmelee Selvaraji, Jasmine Mosberger, David Y Fann, Mitchell Kp Lai, Christopher Li Hsian Chen, Thiruma V Arumugam
{"title":"Unveiling the Therapeutic Promise of Epigenetics in Vascular Cognitive Impairment and Vascular Dementia.","authors":"Sharmelee Selvaraji, Jasmine Mosberger, David Y Fann, Mitchell Kp Lai, Christopher Li Hsian Chen, Thiruma V Arumugam","doi":"10.14336/AD.2025.0010","DOIUrl":"https://doi.org/10.14336/AD.2025.0010","url":null,"abstract":"<p><p>Vascular dementia (VaD) is a progressive neurodegenerative disease characterized by cognitive decline and memory deficits. Despite its significant prevalence and impact, the pathophysiology of VaD remains poorly understood, and current treatments are limited to symptom management. Emerging evidence highlights the importance of lifestyle-associated risk factors in VaD, emphasizing the role of gene-environment interactions, particularly in the realm of epigenetics. While preclinical studies using animal models have provided valuable insights into epigenetic mechanisms, the translatability of these findings to human clinical settings remains limited, and research into VaD-specific epigenetics is still in its infancy. This review aims to elucidate the intricate interplay between epigenetics and VaD, shedding light on potential therapeutic interventions rooted in epigenetic mechanisms. By synthesizing insights from existing literature, we also discuss the challenges and opportunities in translating preclinical findings into clinically viable treatments, underscoring the need for further research to bridge the gap between animal models and human applications.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447843","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}
Jenelle M Collier, Shamseldin Metwally, Mary McFarland, Sanjana Krishna, Pallavi Kurella, Victoria Fiesler, Mark Stauffer, Gulnaz Begum, Julia Kofler, Dandan Sun
{"title":"Upregulation of Na/H Exchanger in Astrogliosis and Early Alzheimer's Disease Pathogenesis.","authors":"Jenelle M Collier, Shamseldin Metwally, Mary McFarland, Sanjana Krishna, Pallavi Kurella, Victoria Fiesler, Mark Stauffer, Gulnaz Begum, Julia Kofler, Dandan Sun","doi":"10.14336/AD.2024.1294","DOIUrl":"https://doi.org/10.14336/AD.2024.1294","url":null,"abstract":"<p><p>Reactive astrogliosis has been indicated as one of the earliest pathological biomarkers in Alzheimer's Disease (AD) pathology. We previously reported that upregulation of the Na<sup>+</sup>/H<sup>+</sup> exchanger isoform 1 (NHE1) protein in reactive astrocytes contributes to neuroinflammation and cognitive function deficits in murine models of ischemic stroke and vascular stenosis. In this study, we utilized AD human post-mortem and APP/PS1dE9 (APP) transgenic mouse brain tissues to determine whether NHE1 upregulation in astrocytes is associated with AD pathogenesis. In both AD human and APP mouse brain tissues, a significant elevation of NHE1 protein expression was detected in glial fibrillary acidic protein expressing (GFAP<sup>+</sup>) reactive astrocytes in cortical and hippocampal regions, compared to control groups. Furthermore, increased astrocytic NHE1 protein and GFAP protein were detected in proximity to amyloid-beta (Aβ) plaques in APP mouse brains. We then tested the efficacy of pharmacological NHE1 inhibition using its inhibitor, HOE642, in attenuating pathogenesis in APP mice. Vehicle-treated APP mice (APP.Veh) exhibited hyperactive locomotor behavior at 4-months and 7-months of age, compared to wild-type littermates (WT.Veh). In contrast, APP mice-treated with HOE642 (APP.HOE) displayed significantly lower hyperactive locomotor behavior (p&;lt0.01). Additionally, APP.HOE mice showed decreased density of amyloid fibrils. In summary, we detected NHE1 protein upregulation in reactive astrocytes in both AD human and APP brains. Pharmacological inhibition of NHE1 protein attenuated pathological Aβ plaque density, and hyperactive locomotor behaviors in APP mice, highlighting NHE1 as a possible therapeutic target for AD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447849","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}
Jakub Wyroba, Joanna Kochan, Liam Kelley, Sharif Iqbal, Paweł Kordowitzki
{"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}
Markus A Hobert, Niklas Helle, Christopher Siebert, Anton Eisenhauer, Martha Gledhill, Walter Maetzler
{"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}
Alison Basel, Sanat S Bhadsavle, Katherine Z Scaturro, Grace K Parkey, Yava Jones-Hall, Michael C Golding
{"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}