Mechanisms of Ageing and Development最新文献

{"title":"Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus","authors":"Michela Palmisano ,&nbsp;Carla Florencia Ramunno ,&nbsp;Eli Farhat ,&nbsp;Mona Dvir-Ginzberg ,&nbsp;Beat Lutz ,&nbsp;Carmen Ruiz de Almodovar ,&nbsp;Andras Bilkei-Gorzo","doi":"10.1016/j.mad.2024.111954","DOIUrl":"10.1016/j.mad.2024.111954","url":null,"abstract":"<div><p>As organisms age, the activity of the endocannabinoid system in the brain declines, coinciding with increased neuroinflammation and disrupted hypothalamic functions. Notably, cannabinoid receptors type-1 (CB1) are highly expressed in the ventromedial hypothalamic nucleus (VMH) within the mediobasal hypothalamus, a central area of neuroendocrine regulation. This study investigates whether the CB1 receptor influences age-related changes in a brain region-dependent manner. Therefore, we performed stereotaxic injections of rAAV1/2 expressing Cre recombinase in 2-month-old CB1^flox/flox male animals to delete the CB1 gene and in CB1-deficient (CB1-STOP) mice to induce its re-expression. The intensity of pro-inflammatory glial activity, gonadotropin-releasing hormone (GnRH) and insulin-like growth factor-1 receptor (IGF-1R) expression was assessed in the hypothalamus of mice at 18–19 months of age. Site-specific CB1 receptor deletion induced pro-inflammatory glial activity and increased hypothalamic <em>Igf1r</em> mRNA expression. Unexpectedly, GnRH levels remained unaltered. Importantly, rescuing the receptor in null mutant animals had the opposite effect: it reduced pro-inflammatory glial activation and decreased <em>Igf1r</em> mRNA expression without affecting GnRH production. Overall, the study highlights the important role of the CB1 receptor in the VMH in reducing age-related inflammation and modulating IGF-1R signaling.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111954"},"PeriodicalIF":5.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S004763742400054X/pdfft?md5=33f2523946297d859c99ff88b3a16767&pid=1-s2.0-S004763742400054X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases","authors":"Nupur Nagar ,&nbsp;Goutami Naidu ,&nbsp;Santosh Kumar Panda ,&nbsp;Khushboo Gulati ,&nbsp;Ravindra Pal Singh ,&nbsp;Krishna Mohan Poluri","doi":"10.1016/j.mad.2024.111944","DOIUrl":"10.1016/j.mad.2024.111944","url":null,"abstract":"<div><p>Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111944"},"PeriodicalIF":5.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT-associated attenuation of cellular senescence in vascular wall","authors":"Iliyana Sazdova ,&nbsp;Nikola Hadzi-Petrushev ,&nbsp;Milena Keremidarska-Markova ,&nbsp;Radoslav Stojchevski ,&nbsp;Ramadan Sopi ,&nbsp;Stanislav Shileiko ,&nbsp;Vadim Mitrokhin ,&nbsp;Hristo Gagov ,&nbsp;Dimitar Avtanski ,&nbsp;Lubomir T. Lubomirov ,&nbsp;Mitko Mladenov","doi":"10.1016/j.mad.2024.111943","DOIUrl":"10.1016/j.mad.2024.111943","url":null,"abstract":"<div><p>This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gene expression patterns and trigger cell growth arrest. SIRT1 has been highlighted for its potential to reduce cellular senescence through modulation of multiple signaling cascades, particularly the endothelial nitric oxide (eNOS)/NO signaling pathway. It also modulates cell cycle through p53 inactivation and suppresses NF-κB mediated expression of adhesive molecules at the vascular level. The study also examines the therapeutic potential of sirtuin modulation in vascular health, identifying SIRT1 and its sirtuin counterparts as potential targets for reducing vascular aging. This study sheds light on the molecular basis of vascular aging and the beneficial effects of sirtuins, paving the way for the development of tailored therapies aimed at enhancing vascular health and prolonging life.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"220 ","pages":"Article 111943"},"PeriodicalIF":5.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the (epi)genetic dysregulation in Parkinson's disease through an integrative brain competitive endogenous RNA network","authors":"Rafael Mina Piergiorge ,&nbsp;Ana Tereza Ribeiro de Vasconcelos ,&nbsp;Cíntia Barros Santos-Rebouças","doi":"10.1016/j.mad.2024.111942","DOIUrl":"10.1016/j.mad.2024.111942","url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a rapidly growing neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra <em>pars compacta</em> (SN) and aggregation of α-synuclein. Its aetiology involves a multifaceted interplay among genetic, environmental, and epigenetic factors. We integrated brain gene expression data from PD patients to construct a comprehensive regulatory network encompassing messenger RNAs (mRNAs), microRNAs (miRNAs), circular RNAs (circRNAs) and, for the first time, RNA binding proteins (RBPs). Expression data from the SN of PD patients and controls were systematically selected from public databases to identify combined differentially expressed genes (DEGs). Brain co-expression analysis revealed modules comprising significant DEGs that function cooperatively. The relationships among co-expressed DEGs, miRNAs, circRNAs, and RBPs revealed an intricate competitive endogenous RNA (ceRNA) network responsible for post-transcriptional dysregulation in PD. Many genes in the ceRNA network, including the <em>TOMM20</em> and <em>HMGCR</em> genes, overlap with the most relevant genes in our previous Alzheimer’s disease-associated ceRNA network, suggesting common underlying mechanisms between both conditions. Moreover, in the ceRNA subnetwork, the RBP Aly/REF export factor (ALYREF), which acts as an RNA 5-methylcytosine(m5C)-binding protein, stood out. Our data sheds new light on the potential role of brain ceRNA networks in PD pathogenesis.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111942"},"PeriodicalIF":5.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcopenia: A dive into metabolism to promote a multimodal, preventive, and regenerative approach","authors":"Virginia Boccardi","doi":"10.1016/j.mad.2024.111941","DOIUrl":"10.1016/j.mad.2024.111941","url":null,"abstract":"<div><p>Sarcopenia, the age-related loss of skeletal muscle mass and function, poses a significant challenge in the field of geriatrics and gerontology, impacting the health and independence of older adults. Understanding and addressing sarcopenia is crucial for optimizing clinical outcomes and enhancing the quality of life along with aging. By synthesizing current research findings and theoretical frameworks, this review elucidates the multifaceted mechanisms underlying sarcopenia, mainly focusing on energy balance and metabolic processes. Furthermore, the manuscript explores the implications of sarcopenia on overall health outcomes, functional decline, and quality of life in older individuals. The study concludes with a perspective on the role of preventive and regenerative medicine in sarcopenia, where the two main lifestyle pillars (exercise and diet) represent key factors.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111941"},"PeriodicalIF":5.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000411/pdfft?md5=8a870c8a1422b1e90f4e74dcfb0dd411&pid=1-s2.0-S0047637424000411-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive variant analysis of phospholipase A2 superfamily genes in large Chinese Parkinson’ s disease cohorts","authors":"Jiabin Liu ,&nbsp;Yige Wang ,&nbsp;Yuwen Zhao ,&nbsp;Hongxu Pan ,&nbsp;Zhenhua Liu ,&nbsp;Qian Xu ,&nbsp;Shen Lu ,&nbsp;Hong Jiang ,&nbsp;Junling Wang ,&nbsp;Qiying Sun ,&nbsp;Jieqiong Tan ,&nbsp;Xinxiang Yan ,&nbsp;Jinchen Li ,&nbsp;Beisha Tang ,&nbsp;Jifeng Guo","doi":"10.1016/j.mad.2024.111940","DOIUrl":"10.1016/j.mad.2024.111940","url":null,"abstract":"<div><p>To clarify the genetic role of phospholipase A2 (PLA2) genes in Parkinson's disease (PD), we performed a genetic association study in large Chinese population cohorts using next-generation sequencing. In this study, we analyzed both rare and common variants of 38 phospholipase A2 genes in two large cohorts. We detected 1558 and 1115 rare variants in these two cohorts, respectively. In both cohorts, we observed suggestive associations between specific subgroups and the risk of PD. At the single-gene level, several genes (<em>PLA2G2D, PLA2G12A, PLA2G12B, PLA2G4F, PNPLA1, PNPLA3, PNPLA7, PLA2G7, PLA2G15, PLAAT5,</em> and <em>ABHD12</em>) are suggestively associated with PD. Meanwhile, 364 and 2261 common variants were identified in two cohorts, respectively. Our study has expanded the genetic spectrum of the PLA2 family genes and suggested potential pathogenetic roles of PLA2 superfamily in PD.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111940"},"PeriodicalIF":5.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites","authors":"Neda Heidari ,&nbsp;Susan Sandeman ,&nbsp;Marcus Dymond ,&nbsp;Chloe Rogers ,&nbsp;Elizabeth L. Ostler ,&nbsp;Richard GA Faragher","doi":"10.1016/j.mad.2024.111938","DOIUrl":"10.1016/j.mad.2024.111938","url":null,"abstract":"<div><p>Progressive liver disease and dysfunction cause toxic metabolites including ammonia and unconjugated bilirubin to accumulate in plasma. As the population ages alternatives to liver transplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function. However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable. Hypothesizing that this loss of core hepatocyte phenotypes was caused by cell senescence we exposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analog incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesise albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2–5 µM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111938"},"PeriodicalIF":5.3,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000381/pdfft?md5=e2f136e12243c0cca551ca1d405527a6&pid=1-s2.0-S0047637424000381-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammaging score as a potential prognostic tool for cancer: A population-based cohort study","authors":"Hailun Xie ,&nbsp;Lishuang Wei ,&nbsp;Guotian Ruan ,&nbsp;Heyang Zhang ,&nbsp;Hanping Shi","doi":"10.1016/j.mad.2024.111939","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111939","url":null,"abstract":"<div><p>This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%–17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111939"},"PeriodicalIF":5.3,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “A feasibility study of the combination of intranasal insulin with dulaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design” [Mech. Ageing Dev. 213 (2023) 111825]","authors":"Tal Davidy ,&nbsp;Iscka Yore ,&nbsp;Tali Cukierman-Yaffe ,&nbsp;Ramit Ravona-Springer ,&nbsp;Abigail Livny ,&nbsp;Orit H. Lesman-Segev ,&nbsp;Yossi Azuri ,&nbsp;Owen Carmichael ,&nbsp;Dimitrios Kapogiannis ,&nbsp;Henrik Zetterberg ,&nbsp;HungMo Lin ,&nbsp;Mary Sano ,&nbsp;Michal Schnaider Beeri","doi":"10.1016/j.mad.2024.111937","DOIUrl":"10.1016/j.mad.2024.111937","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111937"},"PeriodicalIF":5.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S004763742400037X/pdfft?md5=8486f904a09f892f59712b3c078b2f98&pid=1-s2.0-S004763742400037X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience","authors":"Md Ariful Islam ,&nbsp;Ujala Sehar ,&nbsp;Omme Fatema Sultana ,&nbsp;Upasana Mukherjee ,&nbsp;Malcolm Brownell ,&nbsp;Sudhir Kshirsagar ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.mad.2024.111936","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111936","url":null,"abstract":"<div><p>Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called ‘Centenarians” and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as \"SuperAgers\" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111936"},"PeriodicalIF":5.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}