Aging and Disease最新文献

{"title":"TBC1D15 Inhibits Autophagy of Microglia through Maintaining the Damaged Swelling Lysosome in Alzheimer's Disease.","authors":"You Wu, Yong-Ming Zhou, Wei Wu, Wan-Rong Jiang, Xin-Yuan Zhang, Si-Yuan Song, Zhao-Hui Yao","doi":"10.14336/AD.2024.1373","DOIUrl":"https://doi.org/10.14336/AD.2024.1373","url":null,"abstract":"<p><p>Autophagy in microglia is essential for the clearance of amyloid-beta (Aβ) and amyloid plaques in Alzheimer's disease. However, reports regarding the levels of autophagy in microglia have been inconsistent; some studies indicate an early enhancement followed by a subsequent reduction, while others describe a persistently weakened state. Notably, there is a lack of systematic studies documenting the temporal changes in microglial autophagy. TBC1D15, a Rab GTPase, plays a crucial role in lysosomal membrane repair, yet its function in regulating microglial autophagy in Alzheimer's disease remains unexplored. Current research suggests that microglial autophagy is activated in 3-month-old AD mice but gradually decreases by 12 months of age. Furthermore, TBC1D15 levels are significantly elevated in the lysosomes of microglia in Alzheimer's disease. Silencing TBC1D15 markedly inhibits swelling and Aβ phagocytosis in BV2 cells following Aβ treatment while simultaneously promoting autophagy and lysophagy. LIMP II/ATG8-TBC1D15-Dynamin2/RAB7 might participate in lysosome swelling of microglia in AD. These findings indicate that TBC1D15 in microglia is critical for the decline of autophagy in Alzheimer's disease. It is suggested that targeting microglial TBC1D15 may be an important strategy for enhancing autophagy, which facilitates the clearance of amyloid plaques as a therapeutic approach for Alzheimer's disease.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982459","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":"Targeting Astrogliosis in the Retrotrapezoid Nucleus: A Novel Approach to Ameliorate Respiratory Dysfunction and Alzheimer's Pathology in Mice.","authors":"Zahid Iqbal, Ahmad El Hamamy, Ngoc Mai Le, Arya Ranjan, YuXing Zhang, Li Qi, Bharti Manwani, Chunfeng Tan, Louise D McCullough, Jun Li","doi":"10.14336/AD.2024.0523","DOIUrl":"10.14336/AD.2024.0523","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a leading cause of dementia, is associated with significant respiratory dysfunctions. Our study explores the role of astrogliosis in the brainstem retrotrapezoid nucleus (RTN), a key breathing regulatory center, and its impact on breathing control and AD pathology in mice. Using Tg-2576 AD and wild-type mice, we investigated the effect of silencing the transforming growth factor-beta receptor II (TGFβR II) in the RTN. We performed behavioral tests, including the Barnes maze and novel object recognition test, along with whole-body plethysmography to assess breathing disorders. Our results showed that AD mice exhibited increased apneas and cognitive impairment, which were significantly mitigated following TGFβR II gene silencing. Immunohistochemistry revealed elevated levels of GFAP and TGFβR II in the RTN of AD mice, which were reduced post-gene silencing, alongside a decrease in amyloid-beta expression in the cortex and hippocampus. These findings suggest that targeting astrogliosis and improving respiratory control may offer a novel therapeutic avenue for managing Alzheimer's disease. Our study provides the first mechanistic insights into how TGFβ signaling influences both respiratory control and AD pathogenesis, highlighting the potential benefits of stabilizing breathing patterns in AD treatment.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982458","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":"Addressing Healthy Aging: Time to Stop a Tsunami of Rising Alzheimer's Disease.","authors":"Nobel Chenggong Zong, Yuhan Zhang, Yuanli Huang, Hua Cai","doi":"10.14336/AD.2024.1476","DOIUrl":"https://doi.org/10.14336/AD.2024.1476","url":null,"abstract":"<p><p>Alzheimer's disease [AD] disproportionately affects our seniors, diminishing their health and life expectancy. As the world population grows older, the collective burden of AD has become unsustainable. Globally, there were 43.8 million patients in 2016, with a projection of affecting 152 million by 2050. Recent discoveries have shown that molecular changes characteristic to AD manifested 20 years before discernable neurological phenotypes emerge. It is feasible to halt or reverse this pathological process before reaching an irremediable stage. To take advantage of this treatment window, we need to make rapid progress in early detection and monitoring, targeted implementation of preventative measures, invention of novel therapeutics, and pragmatic ramping-up of relevant supporting policies. PET is a powerful tool for prognosis. The utilization of AI technology, on the other hand, has favorable features of low cost per capita, easy dissemination and broad scale data collection to uncover previously unknown hotspots or risk factors. FDA approved drugs, lecanemab and donanemab, have started to show efficacy to put a pause on AD progression. Additional clinical data will enable comprehensive evaluation of the impacts of these drugs. Gene therapy holds the potential of eliciting long term protection, while several candidate loci have been identified. The urgency of a tsunami of rising AD epidemiology demands rapid actions on all fronts of advanced diagnostics, monitoring, preventative and interventive strategies.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982451","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":"Decoding the Multiple Identities and Crosstalk of Organokines in Obesity-Related Type 2 Diabetes Mellitus.","authors":"Yu-Qing Ni, Jun-Kun Zhan, You-Shuo Liu","doi":"10.14336/AD.2024.1138","DOIUrl":"https://doi.org/10.14336/AD.2024.1138","url":null,"abstract":"<p><p>Obesity causes an imbalance in the expression and secretion of several organokines, which in turn contributes to the development of metabolic disorders such as type 2 diabetes mellitus. Organokines are produced by corresponding organs and affect systemic metabolic homeostasis. Diverse organokines play a crucial role in the communication between adipose tissue, skeletal muscle and other organs. In this review, we discuss the biological properties of specific organokines such as adipokines, hepatokines, and myokines. We also highlight the cumulative roles and crosstalk of organokines in obesity-related T2DM. Moreover, we attempt to identify the diagnostic and therapeutic potential of obesity-related T2DM from the perspective of organokines.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982489","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":"Mechanisms Underlying Vascular Inflammaging: Current Insights and Potential Treatment Approaches.","authors":"Ying Zeng, Francesco Buonfiglio, Jingyan Li, Norbert Pfeiffer, Adrian Gericke","doi":"10.14336/AD.2024.0922","DOIUrl":"https://doi.org/10.14336/AD.2024.0922","url":null,"abstract":"<p><p>Inflammaging refers to chronic, low-grade inflammation that becomes more common with age and plays a central role in the pathophysiology of various vascular diseases. Key inflammatory mediators involved in inflammaging contribute to endothelial dysfunction and accelerate the progression of atherosclerosis. In addition, specific pathological mechanisms and the role of inflammasomes have emerged as critical drivers of immune responses within the vasculature. A comprehensive understanding of these processes may lead to innovative treatment strategies that could significantly improve the management of age-related vascular diseases. Emerging therapeutic approaches, including cytokine inhibitors, senolytics, and specialized pro-resolving mediators, aim to counteract inflammaging and restore vascular health. This review seeks to provide an in-depth exploration of the molecular pathways underlying vascular inflammaging and highlight potential therapeutic interventions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982454","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":"Circulating Endocannabinoids and Cognitive Function in Older Adults.","authors":"Shiraz Vered, Alexa S Beiser, Liron Sulimani, Sharon Sznitman, Saptaparni Ghosh, Gil M Lewitus, David Meiri, Sudha Seshadri, Galit Weinstein","doi":"10.14336/AD.2024.1427","DOIUrl":"https://doi.org/10.14336/AD.2024.1427","url":null,"abstract":"<p><p>The role of endogenous cannabinoids (endocannabinoids; eCBs) in cognitive-related processes has been demonstrated in preclinical studies. However, observational studies are lacking. We examined the associations of multiple circulating eCBs and eCB-like molecules with cognitive function in a sample of dementia-free older adults. In this exploratory, cross-sectional study, serum levels of 44 eCBs were analyzed in 237 older participants of the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014). Linear regression models were used to examine the associations of eCB levels with cognitive function while adjusting for potential confounders and correcting for multiple testing. Effect modification by sex and apolipoprotein ε4 (ApoEε4) was additionally examined. Participants' mean age was 73.3±6.2y and 40% were men. After correction for multiple comparisons, increased levels of linoleic acid, linolenic acid, oleic acid, oleoyl alanine and palmitoyl alanine were associated with poorer executive function (B±SE=-0.0002±0.0001, p=0.002; B±SE=-0.0005±0.0001, p<0.001; B±SE=-0.0002±0.0001, p=0.003; B±SE=-0.74±0.25, p=0.003 and B±SE=-1.75±0.62, p=0.005, respectively). In addition, elevated levels of linolenoyl amide and linoleoyl amide were associated with poorer verbal memory (B±SE=-1.45±0.44, p=0.001 and B±SE=-0.16±0.05, p<0.001, respectively) and attention (B±SE=-0.12±0.04, p<0.001 and B±SE=-0.013±0.004, p<0.001, respectively). A significant interaction with sex was observed such that most of the above associations were present only among women. Furthermore, associations between several eCBs and perceptual organization were observed only among participants with ApoEε4 genotype. We identified novel eCB compounds that may be related to cognitive function. Validation of these findings is warranted and should consider sex and ApoEε4 interactions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982488","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":"Unraveling the ROS-Inflammation-Immune Balance: A New Perspective on Aging and Disease.","authors":"Sihang Fang, Mingjun Jiang, Juan Jiao, Hongye Zhao, Dizhi Liu, Danni Gao, Tenger Wang, Ze Yang, Huiping Yuan","doi":"10.14336/AD.2024.1253","DOIUrl":"https://doi.org/10.14336/AD.2024.1253","url":null,"abstract":"<p><p>Increased entropy is a common cause of disease and aging. Lifespan entropy is the overall increase in disorder caused by a person over their lifetime. Aging leads to the excessive production of reactive oxygen species (ROS), which damage the antioxidant system and disrupt redox balance. Organ aging causes chronic inflammation, disrupting the balance of proinflammatory and anti-inflammatory factors. Inflammaging, which is a chronic low-grade inflammatory state, is activated by oxidative stress and can lead to immune system senescence. During this process, entropy increases significantly as the body transitions from a state of low order to high disorder. However, the connection among inflammation, aging, and immune system activity is still not fully understood. This review introduces the idea of the ROS-inflammation-immune balance for the first time and suggests that this balance may be connected to aging and the development of age-related diseases. We also explored how the balance of these three factors controls and affects age-related diseases. Moreover, imbalance in the relationship described above disrupts the regular structures of cells and alters their functions, leading to cellular damage and the emergence of a disorganized state marked by increased entropy. Maintaining a low entropy state is crucial for preventing and reversing aging processes. Consequently, we examined the current preclinical evidence for antiaging medications that target this balance. Ultimately, comprehending the intricate relationships between these three factors and the risk of age-related diseases in organisms will aid in the development of clinical interventions that promote long-term health.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982460","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":"Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.","authors":"Camila Cerna, Nicole Vidal-Herrera, Francisco Silva-Olivares, Daniela Álvarez, Camila González-Arancibia, Miltha Hidalgo, Pabla Aguirre, José González-Urra, Camila Astudillo-Guerrero, Michel Jara, Omar Porras, Gonzalo Cruz, Christian Hodar, Paola Llanos, Pamela Urrutia, Claudia Ibacache-Quiroga, Yulia Nevzorova, Francisco Javier Cubero, Marco Fuenzalida, Samanta Thomas-Valdés, Gonzalo Jorquera","doi":"10.14336/AD.2024.1089","DOIUrl":"https://doi.org/10.14336/AD.2024.1089","url":null,"abstract":"<p><p>The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982490","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":"Alpha-Glucosidase Inhibitors in Aging and Aging-Related Diseases: Clinical Applications and Relevant Mechanisms.","authors":"Ling Zhong, Jielin Yang, Jibran Nehal Syed, Yuwei Zhang, Yan Tian, Xianghui Fu","doi":"10.14336/AD.2024.1477","DOIUrl":"https://doi.org/10.14336/AD.2024.1477","url":null,"abstract":"<p><p>Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918875","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":"Circadian Rhythms and Lung Cancer in the Context of Aging: A Review of Current Evidence.","authors":"Wenhui Xu, Lei Li, Zhendong Cao, Jinghong Ye, Xuyu Gu","doi":"10.14336/AD.2024.1188","DOIUrl":"https://doi.org/10.14336/AD.2024.1188","url":null,"abstract":"<p><p>Circadian rhythm is the internal homeostatic physiological clock that regulates the 24-hour sleep/wake cycle. This biological clock helps to adapt to environmental changes such as light, dark, temperature, and behaviors. Aging, on the other hand, is a process of physiological changes that results in a progressive decline in cells, tissues, and other vital systems of the body. Both aging and the circadian clock are highly interlinked phenomena with a bidirectional relationship. The process of aging leads to circadian disruptions while dysfunctional circadian rhythms promote age-related complications. Both processes involve diverse physiological, molecular, and cellular changes such as modifications in the DNA repair mechanisms, mechanisms, ROS generation, apoptosis, and cell proliferation. This review aims to examine the role of aging and circadian rhythms in the context of lung cancer. This will also review the existing literature on the role of circadian disruptions in the process of aging and vice versa. Various molecular pathways and genes such as BMAL1, SIRT1, HLF, and PER1 and their implications in aging, circadian rhythms, and lung cancer will also be discussed.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982487","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}