Pub Date : 2024-08-05DOI: 10.1038/s41514-024-00162-4
Siting Ye, Shuo Ma, Shunming Liu, Yu Huang, Dantong Li, Min Li, Ting Su, Jing Luo, Chi Zhang, Danli Shi, Lianting Hu, Lei Zhang, Honghua Yu, Mingguang He, Xianwen Shang, Xueli Zhang
The comorbidity of Alzheimer's disease (AD) and age-related macular degeneration (AMD) has been established in clinical and genetic studies. There is growing interest in determining the shared environmental factors associated with both conditions. Recent advancements in record linkage techniques enable us to identify the contributing factors to AD and AMD from a wide range of variables. As such, we first constructed a knowledge graph based on the literature, which included all statistically significant risk factors for AD and AMD. An environment-wide association study (EWAS) was conducted to assess the contribution of various environmental factors to the comorbidity of AD and AMD based on the UK biobank. Based on the conditional Q-Q plots and Bayesian algorithm, several shared environmental factors were identified, which could be categorized into the domains of health condition, biological sample parameters, body index, and attendance availability. Finally, we generated a shared etiology landscape for AD and AMD by combining existing knowledge with our novel findings.
阿尔茨海默病(AD)和老年性黄斑变性(AMD)的并发症已在临床和遗传学研究中得到证实。人们对确定与这两种疾病相关的共同环境因素越来越感兴趣。记录关联技术的最新进展使我们能够从广泛的变量中找出导致 AD 和 AMD 的因素。因此,我们首先根据文献构建了一个知识图谱,其中包括了所有在统计学上对注意力缺失症和老年痴呆症有重要意义的风险因素。在英国生物库的基础上,我们进行了全环境关联研究(EWAS),以评估各种环境因素对AD和AMD合并症的影响。根据条件Q-Q图和贝叶斯算法,我们确定了几个共同的环境因素,它们可分为健康状况、生物样本参数、身体指数和出勤率等领域。最后,我们将现有知识与我们的新发现相结合,得出了AD和AMD的共同病因图谱。
{"title":"Shared whole environmental etiology between Alzheimer's disease and age-related macular degeneration.","authors":"Siting Ye, Shuo Ma, Shunming Liu, Yu Huang, Dantong Li, Min Li, Ting Su, Jing Luo, Chi Zhang, Danli Shi, Lianting Hu, Lei Zhang, Honghua Yu, Mingguang He, Xianwen Shang, Xueli Zhang","doi":"10.1038/s41514-024-00162-4","DOIUrl":"10.1038/s41514-024-00162-4","url":null,"abstract":"<p><p>The comorbidity of Alzheimer's disease (AD) and age-related macular degeneration (AMD) has been established in clinical and genetic studies. There is growing interest in determining the shared environmental factors associated with both conditions. Recent advancements in record linkage techniques enable us to identify the contributing factors to AD and AMD from a wide range of variables. As such, we first constructed a knowledge graph based on the literature, which included all statistically significant risk factors for AD and AMD. An environment-wide association study (EWAS) was conducted to assess the contribution of various environmental factors to the comorbidity of AD and AMD based on the UK biobank. Based on the conditional Q-Q plots and Bayesian algorithm, several shared environmental factors were identified, which could be categorized into the domains of health condition, biological sample parameters, body index, and attendance availability. Finally, we generated a shared etiology landscape for AD and AMD by combining existing knowledge with our novel findings.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"36"},"PeriodicalIF":4.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895150","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}
Pub Date : 2024-07-20DOI: 10.1038/s41514-024-00157-1
Jéssica D Hense, José V V Isola, Driele N Garcia, Larissa S Magalhães, Michal M Masternak, Michael B Stout, Augusto Schneider
This review explores the relationship between ovarian aging and senescent cell accumulation, as well as the efficacy of senolytics to improve reproductive longevity. Reproductive longevity is determined by the age-associated decline in ovarian reserve, resulting in reduced fertility and eventually menopause. Cellular senescence is a state of permanent cell cycle arrest and resistance to apoptosis. Senescent cells accumulate in several tissues with advancing age, thereby promoting chronic inflammation and age-related diseases. Ovaries also appear to accumulate senescent cells with age, which might contribute to aging of the reproductive system and whole organism through SASP production. Importantly, senolytic drugs can eliminate senescent cells and may present a potential intervention to mitigate ovarian aging. Herein, we review the current literature related to the efficacy of senolytic drugs for extending the reproductive window in mice.
{"title":"The role of cellular senescence in ovarian aging.","authors":"Jéssica D Hense, José V V Isola, Driele N Garcia, Larissa S Magalhães, Michal M Masternak, Michael B Stout, Augusto Schneider","doi":"10.1038/s41514-024-00157-1","DOIUrl":"10.1038/s41514-024-00157-1","url":null,"abstract":"<p><p>This review explores the relationship between ovarian aging and senescent cell accumulation, as well as the efficacy of senolytics to improve reproductive longevity. Reproductive longevity is determined by the age-associated decline in ovarian reserve, resulting in reduced fertility and eventually menopause. Cellular senescence is a state of permanent cell cycle arrest and resistance to apoptosis. Senescent cells accumulate in several tissues with advancing age, thereby promoting chronic inflammation and age-related diseases. Ovaries also appear to accumulate senescent cells with age, which might contribute to aging of the reproductive system and whole organism through SASP production. Importantly, senolytic drugs can eliminate senescent cells and may present a potential intervention to mitigate ovarian aging. Herein, we review the current literature related to the efficacy of senolytic drugs for extending the reproductive window in mice.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"35"},"PeriodicalIF":4.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736221","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}
Pub Date : 2024-07-18DOI: 10.1038/s41514-024-00160-6
Sophie J Hopkin, Poppy Nathan, Laleh Pezhman, Jenefa Begum, Julia E Manning, Lauren M Quinn, G Ed Rainger, Helen M McGettrick, Asif J Iqbal, Myriam Chimen
Inflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.
{"title":"Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention.","authors":"Sophie J Hopkin, Poppy Nathan, Laleh Pezhman, Jenefa Begum, Julia E Manning, Lauren M Quinn, G Ed Rainger, Helen M McGettrick, Asif J Iqbal, Myriam Chimen","doi":"10.1038/s41514-024-00160-6","DOIUrl":"10.1038/s41514-024-00160-6","url":null,"abstract":"<p><p>Inflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"33"},"PeriodicalIF":4.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725423","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}
Pub Date : 2024-07-15DOI: 10.1038/s41514-024-00159-z
Magnolia G Wang, Patrick Seale, David Furman
Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity. In particular, the infrapatellar fat pad (IFP), located in the knee joint, which provides a protective cushion for joint loading, also secretes multiple endocrine factors and inflammatory cytokines (inflammaging) that can regulate joint physiology and disease. Correlates of cartilage degeneration and OA-associated disease severity include inflammation and fibrosis of IFP in model organisms and human studies. In this article, we discuss recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA.
骨关节炎(OA)是最常见的关节炎,仅在美国每年的医疗支出就接近 1400 亿美元。肥胖、衰老和关节损伤是导致 OA 发生和发展的主要风险因素,但其病理机制仍不清楚。新的证据表明,关节组织(包括关节内脂肪组织储库)中的细胞失调和炎症可能会导致疾病的严重程度。特别是位于膝关节内的髌下脂肪垫(IFP),它为关节负荷提供保护性缓冲,同时也分泌多种内分泌因子和炎症细胞因子(炎症aging),可调节关节生理和疾病。在模型生物和人体研究中,软骨退化和 OA 相关疾病严重程度的相关因素包括 IFP 的炎症和纤维化。在本文中,我们将讨论在了解关节内脂肪组织在调节关节生物学和 OA 方面的作用和调控方面的最新进展。
{"title":"The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis.","authors":"Magnolia G Wang, Patrick Seale, David Furman","doi":"10.1038/s41514-024-00159-z","DOIUrl":"10.1038/s41514-024-00159-z","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity. In particular, the infrapatellar fat pad (IFP), located in the knee joint, which provides a protective cushion for joint loading, also secretes multiple endocrine factors and inflammatory cytokines (inflammaging) that can regulate joint physiology and disease. Correlates of cartilage degeneration and OA-associated disease severity include inflammation and fibrosis of IFP in model organisms and human studies. In this article, we discuss recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"34"},"PeriodicalIF":4.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622061","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}
Pub Date : 2024-07-10DOI: 10.1038/s41514-024-00161-5
D Jothi, Linda Anna Michelle Kulka
The ability to reprogram patient-derived-somatic cells to IPSCs (Induced Pluripotent Stem Cells) has led to a better understanding of aging and age-related diseases like Parkinson's, and Alzheimer's. The established patient-derived disease models mimic disease pathology and can be used to design drugs for aging and age-related diseases. However, the age and genetic mutations of the donor cells, the employed reprogramming, and the differentiation protocol might often pose challenges in establishing an appropriate disease model. In this review, we will focus on the various strategies for the successful reprogramming and differentiation of patient-derived cells to disease models for aging and age-related diseases, emphasizing the accuracy in the recapitulation of disease pathology and ways to overcome the limitations of its potential application in cell replacement therapy and drug development.
{"title":"Strategies for modeling aging and age-related diseases.","authors":"D Jothi, Linda Anna Michelle Kulka","doi":"10.1038/s41514-024-00161-5","DOIUrl":"10.1038/s41514-024-00161-5","url":null,"abstract":"<p><p>The ability to reprogram patient-derived-somatic cells to IPSCs (Induced Pluripotent Stem Cells) has led to a better understanding of aging and age-related diseases like Parkinson's, and Alzheimer's. The established patient-derived disease models mimic disease pathology and can be used to design drugs for aging and age-related diseases. However, the age and genetic mutations of the donor cells, the employed reprogramming, and the differentiation protocol might often pose challenges in establishing an appropriate disease model. In this review, we will focus on the various strategies for the successful reprogramming and differentiation of patient-derived cells to disease models for aging and age-related diseases, emphasizing the accuracy in the recapitulation of disease pathology and ways to overcome the limitations of its potential application in cell replacement therapy and drug development.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"32"},"PeriodicalIF":4.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581909","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}
Pub Date : 2024-06-20DOI: 10.1038/s41514-024-00151-7
Saba Amiri, Monica van den Berg, Mohammad-Reza Nazem-Zadeh, Marleen Verhoye, Mahmood Amiri, Georgios A Keliris
This study investigates brain network alterations in the default mode-like network (DMLN) at early stages of disease progression in a rat model of Alzheimer's disease (AD) with application in the development of early diagnostic biomarkers of AD in translational studies. Thirteen male TgF344-AD (TG) rats, and eleven male wild-types (WT) littermates underwent longitudinal resting-state fMRI at the age of 4 and 6 months (pre and early-plaque stages of AD). Alterations in connectivity within DMLN were characterized by calculating the nodal degree (ND), a graph theoretical measure of centrality. The ND values of the left CA2 subregion of the hippocampus was found to be significantly lower in the 4-month-old TG cohort compared to the age-matched WT littermates. Moreover, a lower ND value (hypo-connectivity) was observed in the right prelimbic cortex (prL) and basal forebrain in the 6-month-old TG cohort, compared to the same age WT cohort. Indeed, the ND pattern in the DMLN in both TG and WT cohorts showed significant differences across the two time points that represent pre-plaque and early plaque stages of disease progression. Our findings indicate that lower nodal degree (hypo-connectivity) in the left CA2 in the pre-plaque stage of AD and hypo-connectivity between the basal forebrain and the DMLN regions in the early-plaque stage demonstrated differences in comparison to healthy controls. These results suggest that a graph-theoretical measure such as the nodal degree, can characterize brain networks and improve our insights into the mechanisms underlying Alzheimer's disease.
{"title":"Nodal degree centrality in the default mode-like network of the TgF344-AD Alzheimer's disease rat model as a measure of early network alterations.","authors":"Saba Amiri, Monica van den Berg, Mohammad-Reza Nazem-Zadeh, Marleen Verhoye, Mahmood Amiri, Georgios A Keliris","doi":"10.1038/s41514-024-00151-7","DOIUrl":"10.1038/s41514-024-00151-7","url":null,"abstract":"<p><p>This study investigates brain network alterations in the default mode-like network (DMLN) at early stages of disease progression in a rat model of Alzheimer's disease (AD) with application in the development of early diagnostic biomarkers of AD in translational studies. Thirteen male TgF344-AD (TG) rats, and eleven male wild-types (WT) littermates underwent longitudinal resting-state fMRI at the age of 4 and 6 months (pre and early-plaque stages of AD). Alterations in connectivity within DMLN were characterized by calculating the nodal degree (ND), a graph theoretical measure of centrality. The ND values of the left CA2 subregion of the hippocampus was found to be significantly lower in the 4-month-old TG cohort compared to the age-matched WT littermates. Moreover, a lower ND value (hypo-connectivity) was observed in the right prelimbic cortex (prL) and basal forebrain in the 6-month-old TG cohort, compared to the same age WT cohort. Indeed, the ND pattern in the DMLN in both TG and WT cohorts showed significant differences across the two time points that represent pre-plaque and early plaque stages of disease progression. Our findings indicate that lower nodal degree (hypo-connectivity) in the left CA2 in the pre-plaque stage of AD and hypo-connectivity between the basal forebrain and the DMLN regions in the early-plaque stage demonstrated differences in comparison to healthy controls. These results suggest that a graph-theoretical measure such as the nodal degree, can characterize brain networks and improve our insights into the mechanisms underlying Alzheimer's disease.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"29"},"PeriodicalIF":4.1,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433677","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}
Pub Date : 2024-06-20DOI: 10.1038/s41514-024-00158-0
Hyeon-Mu Cho, Se-Hee Choe, Ja-Rang Lee, Hye-Ri Park, Min-Gyeong Ko, Yun-Jung Lee, Hwal-Yong Lee, Sung Hyun Park, Sang-Je Park, Young-Hyun Kim, Jae-Won Huh
Despite the different perspectives by diverse research sectors spanning several decades, aging research remains uncharted territory for human beings. Therefore, we investigated the transcriptomic characteristics of eight male healthy cynomolgus macaques, and the annual sampling was designed with two individuals in four age groups. As a laboratory animal, the macaques were meticulously shielded from all environmental factors except aging. The results showed recent findings of certain immune response and the age-associated network of primate immunity. Three important aging patterns were identified and each gene clusters represented a different immune response. The increased expression pattern was predominantly associated with innate immune cells, such as Neutrophils and NK cells, causing chronic inflammation with aging whereas the other two decreased patterns were associated with adaptive immunity, especially "B cell activation" affecting antibody diversity of aging. Furthermore, the hub gene network of the patterns reflected transcriptomic age and correlated with human illness status, aiding in future human disease prediction. Our macaque transcriptome profiling results offer systematic insights into the age-related immunological features of primates.
尽管几十年来不同研究领域提出了不同的观点,但对于人类来说,衰老研究仍然是一个未知领域。因此,我们研究了八只雄性健康猕猴的转录组特征,每年取样两次,分为四个年龄组。作为实验动物,猕猴被严格控制在除衰老以外的所有环境因素之外。研究结果显示了某些免疫反应和与年龄相关的灵长类免疫网络的最新发现。研究发现了三种重要的衰老模式,每个基因簇代表了不同的免疫反应。表达增加的模式主要与先天性免疫细胞(如中性粒细胞和 NK 细胞)有关,会随着年龄的增长导致慢性炎症;而另外两种表达减少的模式则与适应性免疫有关,尤其是 "B 细胞活化 "会影响衰老过程中的抗体多样性。此外,这些模式的中枢基因网络反映了转录组年龄,并与人类疾病状况相关,有助于未来人类疾病的预测。我们的猕猴转录组分析结果为灵长类动物与年龄相关的免疫学特征提供了系统的见解。
{"title":"Transcriptome analysis of cynomolgus macaques throughout their lifespan reveals age-related immune patterns.","authors":"Hyeon-Mu Cho, Se-Hee Choe, Ja-Rang Lee, Hye-Ri Park, Min-Gyeong Ko, Yun-Jung Lee, Hwal-Yong Lee, Sung Hyun Park, Sang-Je Park, Young-Hyun Kim, Jae-Won Huh","doi":"10.1038/s41514-024-00158-0","DOIUrl":"10.1038/s41514-024-00158-0","url":null,"abstract":"<p><p>Despite the different perspectives by diverse research sectors spanning several decades, aging research remains uncharted territory for human beings. Therefore, we investigated the transcriptomic characteristics of eight male healthy cynomolgus macaques, and the annual sampling was designed with two individuals in four age groups. As a laboratory animal, the macaques were meticulously shielded from all environmental factors except aging. The results showed recent findings of certain immune response and the age-associated network of primate immunity. Three important aging patterns were identified and each gene clusters represented a different immune response. The increased expression pattern was predominantly associated with innate immune cells, such as Neutrophils and NK cells, causing chronic inflammation with aging whereas the other two decreased patterns were associated with adaptive immunity, especially \"B cell activation\" affecting antibody diversity of aging. Furthermore, the hub gene network of the patterns reflected transcriptomic age and correlated with human illness status, aiding in future human disease prediction. Our macaque transcriptome profiling results offer systematic insights into the age-related immunological features of primates.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"30"},"PeriodicalIF":4.1,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433678","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}
Pub Date : 2024-06-20DOI: 10.1038/s41514-024-00154-4
Sanne J M Stefens, Nicole van Vliet, Arne IJpma, Joyce Burger, Yunlei Li, Paula M van Heijningen, Jan H N Lindeman, Danielle Majoor-Krakauer, Hence J M Verhagen, Roland Kanaar, Jeroen Essers, Ingrid van der Pluijm
Aortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4R/R mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4R/R aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4R/R VSMCs by revealing increased SA-β-gal, p21, and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dilated aorta of Fibulin-4R/R|p21-luciferase mice. Our studies identify a cellular aging cascade in Fibulin-4 aneurysmal disease, by revealing that Fibulin-4R/R aortic VSMCs have a pronounced SASP and a senescent phenotype that may underlie aortic wall degeneration. Additionally, we demonstrated the therapeutic effect of JAK/STAT and TGF-β pathway inhibition, as well as senolytic treatment on Fibulin-4R/R VSMCs in vitro. These findings can contribute to improved therapeutic options for aneurysmal disease aimed at reducing senescent cells.
{"title":"Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.","authors":"Sanne J M Stefens, Nicole van Vliet, Arne IJpma, Joyce Burger, Yunlei Li, Paula M van Heijningen, Jan H N Lindeman, Danielle Majoor-Krakauer, Hence J M Verhagen, Roland Kanaar, Jeroen Essers, Ingrid van der Pluijm","doi":"10.1038/s41514-024-00154-4","DOIUrl":"10.1038/s41514-024-00154-4","url":null,"abstract":"<p><p>Aortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4<sup>R/R</sup> mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4<sup>R/R</sup> aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4<sup>R/R</sup> VSMCs by revealing increased SA-β-gal, p21, and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dilated aorta of Fibulin-4<sup>R/R</sup>|p21-luciferase mice. Our studies identify a cellular aging cascade in Fibulin-4 aneurysmal disease, by revealing that Fibulin-4<sup>R/R</sup> aortic VSMCs have a pronounced SASP and a senescent phenotype that may underlie aortic wall degeneration. Additionally, we demonstrated the therapeutic effect of JAK/STAT and TGF-β pathway inhibition, as well as senolytic treatment on Fibulin-4<sup>R/R</sup> VSMCs in vitro. These findings can contribute to improved therapeutic options for aneurysmal disease aimed at reducing senescent cells.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"31"},"PeriodicalIF":4.1,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433676","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}
Pub Date : 2024-06-15DOI: 10.1038/s41514-024-00156-2
Linda Ravazzano, Graziana Colaianni, Anna Tarakanova, Yu-Bai Xiao, Maria Grano, Flavia Libonati
The world population is increasingly aging, deeply affecting our society by challenging our healthcare systems and presenting an economic burden, thus turning the spotlight on aging-related diseases: exempli gratia, osteoporosis, a silent disease until you suddenly break a bone. The increase in bone fracture risk with age is generally associated with a loss of bone mass and an alteration in the skeletal architecture. However, such changes cannot fully explain increased fragility with age. To successfully tackle age-related bone diseases, it is paramount to comprehensively understand the fundamental mechanisms responsible for tissue degeneration. Aging mechanisms persist at multiple length scales within the complex hierarchical bone structure, raising the need for a multiscale and multidisciplinary approach to resolve them. This paper aims to provide an overarching analysis of aging processes in bone and to review the most prominent outcomes of bone aging. A systematic description of different length scales, highlighting the corresponding techniques adopted at each scale and motivating the need for combining diverse techniques, is provided to get a comprehensive description of the multi-physics phenomena involved.
{"title":"Multiscale and multidisciplinary analysis of aging processes in bone.","authors":"Linda Ravazzano, Graziana Colaianni, Anna Tarakanova, Yu-Bai Xiao, Maria Grano, Flavia Libonati","doi":"10.1038/s41514-024-00156-2","DOIUrl":"10.1038/s41514-024-00156-2","url":null,"abstract":"<p><p>The world population is increasingly aging, deeply affecting our society by challenging our healthcare systems and presenting an economic burden, thus turning the spotlight on aging-related diseases: exempli gratia, osteoporosis, a silent disease until you suddenly break a bone. The increase in bone fracture risk with age is generally associated with a loss of bone mass and an alteration in the skeletal architecture. However, such changes cannot fully explain increased fragility with age. To successfully tackle age-related bone diseases, it is paramount to comprehensively understand the fundamental mechanisms responsible for tissue degeneration. Aging mechanisms persist at multiple length scales within the complex hierarchical bone structure, raising the need for a multiscale and multidisciplinary approach to resolve them. This paper aims to provide an overarching analysis of aging processes in bone and to review the most prominent outcomes of bone aging. A systematic description of different length scales, highlighting the corresponding techniques adopted at each scale and motivating the need for combining diverse techniques, is provided to get a comprehensive description of the multi-physics phenomena involved.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328256","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}
Pub Date : 2024-05-21DOI: 10.1038/s41514-024-00150-8
Christopher E Zwilling, Jisheng Wu, Aron K Barbey
The emerging field of Nutritional Cognitive Neuroscience aims to uncover specific foods and nutrients that promote healthy brain aging. Central to this effort is the discovery of nutrient profiles that can be targeted in nutritional interventions designed to promote brain health with respect to multimodal neuroimaging measures of brain structure, function, and metabolism. The present study therefore conducted one of the largest and most comprehensive nutrient biomarker studies examining multimodal neuroimaging measures of brain health within a sample of 100 older adults. To assess brain health, a comprehensive battery of well-established cognitive and brain imaging measures was administered, along with 13 blood-based biomarkers of diet and nutrition. The findings of this study revealed distinct patterns of aging, categorized into two phenotypes of brain health based on hierarchical clustering. One phenotype demonstrated an accelerated rate of aging, while the other exhibited slower-than-expected aging. A t-test analysis of dietary biomarkers that distinguished these phenotypes revealed a nutrient profile with higher concentrations of specific fatty acids, antioxidants, and vitamins. Study participants with this nutrient profile demonstrated better cognitive scores and delayed brain aging, as determined by a t-test of the means. Notably, participant characteristics such as demographics, fitness levels, and anthropometrics did not account for the observed differences in brain aging. Therefore, the nutrient pattern identified by the present study motivates the design of neuroscience-guided dietary interventions to promote healthy brain aging.
营养认知神经科学这一新兴领域旨在发现促进大脑健康老化的特定食物和营养素。这项工作的核心是发现营养成分的特征,以便有针对性地采取营养干预措施,促进大脑结构、功能和新陈代谢等多模态神经影像测量方面的大脑健康。因此,本研究开展了一项规模最大、最全面的营养生物标志物研究,在 100 名老年人样本中对大脑健康的多模态神经影像测量进行了检查。为了评估大脑健康状况,研究人员采用了一整套成熟的认知和大脑成像测量方法,以及 13 种基于血液的饮食和营养生物标志物。这项研究的结果揭示了不同的衰老模式,并根据层次聚类将其分为两种大脑健康表型。一种表型表现出衰老速度加快,而另一种则表现出衰老速度慢于预期。对区分这些表型的膳食生物标志物进行的 t 检验分析表明,特定脂肪酸、抗氧化剂和维生素的浓度较高。根据均值的 t 检验,具有这种营养成分的研究参与者的认知能力得分更高,大脑衰老的时间也更晚。值得注意的是,人口统计学、体能水平和人体测量学等参与者特征并不能解释所观察到的大脑衰老差异。因此,本研究确定的营养模式有助于设计以神经科学为指导的饮食干预措施,以促进大脑的健康老化。
{"title":"Investigating nutrient biomarkers of healthy brain aging: a multimodal brain imaging study.","authors":"Christopher E Zwilling, Jisheng Wu, Aron K Barbey","doi":"10.1038/s41514-024-00150-8","DOIUrl":"10.1038/s41514-024-00150-8","url":null,"abstract":"<p><p>The emerging field of Nutritional Cognitive Neuroscience aims to uncover specific foods and nutrients that promote healthy brain aging. Central to this effort is the discovery of nutrient profiles that can be targeted in nutritional interventions designed to promote brain health with respect to multimodal neuroimaging measures of brain structure, function, and metabolism. The present study therefore conducted one of the largest and most comprehensive nutrient biomarker studies examining multimodal neuroimaging measures of brain health within a sample of 100 older adults. To assess brain health, a comprehensive battery of well-established cognitive and brain imaging measures was administered, along with 13 blood-based biomarkers of diet and nutrition. The findings of this study revealed distinct patterns of aging, categorized into two phenotypes of brain health based on hierarchical clustering. One phenotype demonstrated an accelerated rate of aging, while the other exhibited slower-than-expected aging. A t-test analysis of dietary biomarkers that distinguished these phenotypes revealed a nutrient profile with higher concentrations of specific fatty acids, antioxidants, and vitamins. Study participants with this nutrient profile demonstrated better cognitive scores and delayed brain aging, as determined by a t-test of the means. Notably, participant characteristics such as demographics, fitness levels, and anthropometrics did not account for the observed differences in brain aging. Therefore, the nutrient pattern identified by the present study motivates the design of neuroscience-guided dietary interventions to promote healthy brain aging.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11109270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077516","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}