Mechanisms of Ageing and Development最新文献_第10页

Involvement of miRNA on epigenetics landscape of Parkinson's disease: From pathogenesis to therapeutics miRNA参与帕金森病的表观遗传学景观:从发病机制到治疗

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111826

Sai Nikhil Uppala , Kamatham Pushpa Tryphena , Padmashri Naren , Saurabh Srivastava , Shashi Bala Singh , Dharmendra Kumar Khatri

{"title":"Involvement of miRNA on epigenetics landscape of Parkinson's disease: From pathogenesis to therapeutics","authors":"Sai Nikhil Uppala , Kamatham Pushpa Tryphena , Padmashri Naren , Saurabh Srivastava , Shashi Bala Singh , Dharmendra Kumar Khatri","doi":"10.1016/j.mad.2023.111826","DOIUrl":"10.1016/j.mad.2023.111826","url":null,"abstract":"<div><p><span>The development of novel therapeutics for the effective management of Parkinson’s disease (PD) is undertaken seriously by the scientific community as the burden of PD continues to increase. Several molecular pathways are being explored to identify novel therapeutic targets. Epigenetics is strongly implicated in several </span>neurodegenerative diseases<span><span> (NDDs) including PD. Several epigenetic mechanisms were found to dysregulated in various studies. These mechanisms are regulated by several </span>miRNAs which are associated with a variety of pathogenic mechanisms in PD. This concept is extensively investigated in several cancers but not well documented in PD. Identifying the miRNAs with dual role i.e., regulation of epigenetic mechanisms as well as modulation of proteins implicated in the pathogenesis of PD could pave way for the development of novel therapeutics to target them. These miRNAs could also serve as potential biomarkers and can be useful in the early diagnosis or assessment of disease severity. In this article we would like to discuss about various epigenetic changes operating in PD and how miRNAs are involved in the regulation of these mechanisms and their potential to be novel therapeutic targets in PD.</span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796352","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}

引用次数: 3

Age-associated anatomical and physiological alterations in Caenorhabditis elegans 秀丽隐杆线虫与年龄相关的解剖和生理改变

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111827

Emmanuel Spanoudakis , Nektarios Tavernarakis

引用次数: 1

Prenatal exposure to CB2 receptors agonist differentially impacts male and female germ cells via histone modification 产前暴露于CB2受体激动剂通过组蛋白修饰对男性和女性生殖细胞产生不同的影响

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111840

Alice Zucchi , Elisa Innocenzi , Angelo Onorato , Susanna Dolci , Ambra Colopi , Carmela Rita Balistreri , Paola Grimaldi

{"title":"Prenatal exposure to CB2 receptors agonist differentially impacts male and female germ cells via histone modification","authors":"Alice Zucchi , Elisa Innocenzi , Angelo Onorato , Susanna Dolci , Ambra Colopi , Carmela Rita Balistreri , Paola Grimaldi","doi":"10.1016/j.mad.2023.111840","DOIUrl":"https://doi.org/10.1016/j.mad.2023.111840","url":null,"abstract":"<div><p>Cannabis use during pregnancy is increasing in the last few years potentially because of decreased perception of the risk of harm. Regardless, recent evidence demonstrated that prenatal cannabis exposure is associated with adverse outcomes. To date there is limited evidence of the impact of cannabis exposure during pregnancy on the reproductive health of the offspring. The biological effects of cannabis are mediated by two cannabinoid receptors, CB<sub>1</sub> and CB<sub>2</sub>. We previously demonstrated that CB<sub>2</sub> is highly expressed in mouse male and female fetal germ cells. In this study, we investigated the effects of prenatal exposure to a selective CB<sub>2</sub> agonist, JWH-133, on the long-term reproductive health of male and female offspring and on the involved molecular epigenetic mechanisms. Notably, we focused on epigenetic histone modifications that can silence or activate gene expression, playing a pivotal role in cell differentiation. We reported that prenatal activation of CB<sub>2</sub> has a sex-specific impact on germ cell development of the offspring. In male it determines a delay of germ cell differentiation coinciding with an enrichment of H3K27me3, while in female it causes a reduction of the follicles number through an increased apoptotic process not linked to modified H3K27me3 level.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49855922","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}

引用次数: 1

What do we mean by “aging”? Questions and perspectives revealed by studies in Drosophila 我们所说的“衰老”是什么意思?果蝇研究揭示的问题和观点

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111839

Andrew P.K. Wodrich , Andrew W. Scott , Edward Giniger

{"title":"What do we mean by “aging”? Questions and perspectives revealed by studies in Drosophila","authors":"Andrew P.K. Wodrich , Andrew W. Scott , Edward Giniger","doi":"10.1016/j.mad.2023.111839","DOIUrl":"10.1016/j.mad.2023.111839","url":null,"abstract":"<div><p>What is the nature of aging, and how best can we study it? Here, using a series of questions that highlight differing perspectives about the nature of aging, we ask how data from <span><em>Drosophila melanogaster</em></span> at the organismal, tissue, cellular, and molecular levels shed light on the complex interactions among the phenotypes associated with aging. Should aging be viewed as an individual’s increasing probability of mortality over time or as a progression of physiological states? Are all age-correlated changes in physiology detrimental to vigor or are some compensatory changes that maintain vigor? Why do different age-correlated functions seem to change at different rates in a single individual as it ages? Should aging be considered as a single, integrated process across the scales of biological resolution, from organismal to molecular, or must we consider each level of biological scale as a separate, distinct entity? Viewing aging from these differing perspectives yields distinct but complementary interpretations about the properties and mechanisms of aging and may offer a path through the complexities related to understanding the nature of aging.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176039","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}

引用次数: 0

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 鼻内胰岛素联合杜拉鲁肽治疗老年代谢综合征高危痴呆患者认知功能的可行性研究——研究原理和设计

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111825

Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri

{"title":"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","authors":"Tal Davidy , Iscka Yore , Tali Cukierman-Yaffe , Ramit Ravona-Springer , Abigail Livny , Orit H. Lesman-Segev , Yossi Azuri , Owen Carmichael , Dimitrios Kapogiannis , Henrik Zetterberg , HungMo Lin , Mary Sano , Michal Schnaider Beeri","doi":"10.1016/j.mad.2023.111825","DOIUrl":"10.1016/j.mad.2023.111825","url":null,"abstract":"<div><h3>Introduction</h3><p><span>We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with dulaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and </span>mild cognitive impairment<span> (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits.</span></p></div><div><h3>Methods</h3><p>This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/dulaglutide injection, intranasal placebo/dulaglutide injection, INI/placebo injection, and intranasal placebo/placebo injection. Feasibility of combining INI with dulaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with dulaglutide (1.5 mg/week), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization<span>, white matter hyperintensities, Alzheimer’s related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample.</span></p></div><div><h3>Discussion</h3><p>This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial of the cognitive benefits of the combination of INI with dulaglutide in individuals enriched for CVD and at high dementia risk.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9791742","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}

引用次数: 0

Aging – What it is and how to measure it 衰老——它是什么以及如何衡量它

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111837

Maryam Keshavarz , Kan Xie , Daniele Bano , Dan Ehninger

{"title":"Aging – What it is and how to measure it","authors":"Maryam Keshavarz , Kan Xie , Daniele Bano , Dan Ehninger","doi":"10.1016/j.mad.2023.111837","DOIUrl":"10.1016/j.mad.2023.111837","url":null,"abstract":"<div><p>The current understanding of the biology of aging is largely based on research aimed at identifying factors that influence lifespan. However, lifespan as a sole proxy measure of aging has limitations because it can be influenced by specific pathologies (not generalized physiological deterioration in old age). Hence, there is a great need to discuss and design experimental approaches that are well-suited for studies targeting the biology of aging, rather than the biology of specific pathologies that restrict the lifespan of a given species. For this purpose, we here review various perspectives on aging, discuss agreement and disagreement among researchers on the definition of aging, and show that while slightly different aspects are emphasized, a widely accepted feature, shared across many definitions, is that aging is accompanied by phenotypic changes that occur in a population over the course of an average lifespan. We then discuss experimental approaches that are in line with these considerations, including multidimensional analytical frameworks as well as designs that facilitate the proper assessment of intervention effects on aging rate. The proposed framework can guide discovery approaches to aging mechanisms in all key model organisms (e.g., mouse, fish models, D. melanogaster, C. elegans) as well as in humans.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797794","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}

引用次数: 0

Understanding the roles and regulation of mitochondrial microRNAs (MitomiRs) in neurodegenerative diseases: Current status and advances 了解线粒体microRNAs (MitomiRs)在神经退行性疾病中的作用和调控:现状和进展

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-07-01 DOI: 10.1016/j.mad.2023.111838

Bhaskar Jyoti Saikia , Juhi Bhardwaj , Sangita Paul , Srishti Sharma , Anindita Neog , Swaraj Ranjan Paul , Binukumar BK

{"title":"Understanding the roles and regulation of mitochondrial microRNAs (MitomiRs) in neurodegenerative diseases: Current status and advances","authors":"Bhaskar Jyoti Saikia , Juhi Bhardwaj , Sangita Paul , Srishti Sharma , Anindita Neog , Swaraj Ranjan Paul , Binukumar BK","doi":"10.1016/j.mad.2023.111838","DOIUrl":"10.1016/j.mad.2023.111838","url":null,"abstract":"<div><p><span><span><span><span><span>MicroRNAs (miRNA) are a class of small non-coding RNA, roughly 21–22 </span>nucleotides in length, which are master </span>gene regulators<span>. These miRNAs bind to the mRNA's 3’ - untranslated region<span> and regulate post-transcriptional gene regulation, thereby influencing various physiological and cellular processes. Another class of miRNAs known as mitochondrial miRNA (MitomiRs) has been found to either originate from the mitochondrial genome or be translocated directly into the mitochondria. Although the role of nuclear DNA encoded miRNA in the progression of various </span></span></span>neurological diseases such as </span>Parkinson's disease, Alzheimer’s disease, </span>Huntington's disease<span><span>, etc. is well known, accumulating evidence suggests the possible role of deregulated mitomiRs in the progression of various neurodegenerative diseases with unknown mechanism. We have attempted to outline the current state of mitomiRs role in controlling </span>mitochondrial gene expression and function through this review, paying particular attention to their contribution to neurological processes, their etiology, and their potential therapeutic use.</span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156482","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}

引用次数: 1

Sex differences in adult lifespan and aging rate across mammals: A test of the ‘Mother Curse hypothesis’ 哺乳动物成年寿命和衰老率的性别差异:对“母亲诅咒假说”的检验

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-06-01 DOI: 10.1016/j.mad.2023.111799

Hugo Cayuela , Jean-Michel Gaillard , Cristina Vieira , Victor Ronget , Jérôme M.W. Gippet , Thamar Conde García , Gabriel A.B. Marais , Jean-François Lemaître

{"title":"Sex differences in adult lifespan and aging rate across mammals: A test of the ‘Mother Curse hypothesis’","authors":"Hugo Cayuela , Jean-Michel Gaillard , Cristina Vieira , Victor Ronget , Jérôme M.W. Gippet , Thamar Conde García , Gabriel A.B. Marais , Jean-François Lemaître","doi":"10.1016/j.mad.2023.111799","DOIUrl":"10.1016/j.mad.2023.111799","url":null,"abstract":"<div><p><span>In many animal species, including humans, males have shorter lifespan and show faster survival aging than females. This differential increase in mortality between sexes could result from the accumulation of deleterious mutations in the mitochondrial genome of males due to the maternal mode of mtDNA inheritance. To date, empirical evidence supporting the existence of this mechanism – called the </span><em>Mother Curse hypothesis</em> – remains largely limited to a few study cases in humans and <em>Drosophila</em>. In this study, we tested whether the <em>Mother Curse hypothesis</em> accounts for sex differences in lifespan and aging rate across 128 populations of mammals (60 and 68 populations studied in wild and captive conditions, respectively) encompassing 104 species. We found that adult lifespan decreases with increasing mtDNA neutral substitution rate in both sexes in a similar way in the wild – but not in captivity. Moreover, the aging rate marginally increased with neutral substitution rate in males and females in the wild. Overall, these results indicate that the <em>Mother Curse hypothesis</em><span> is not supported across mammals. We further discuss the implication of these findings for our understanding of the evolution of sex differences in mortality and aging.</span></p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9593465","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}

引用次数: 2

Fecal microbiota transplantation holds the secret to youth 粪便微生物群移植是保持青春的秘诀

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-06-01 DOI: 10.1016/j.mad.2023.111823

Yiming Meng , Jing Sun , Guirong Zhang

引用次数: 4

Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases A-to-I RNA编辑、M6A RNA甲基化和选择性剪接对生理性脑老化和神经退行性疾病的贡献

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2023-06-01 DOI: 10.1016/j.mad.2023.111807

Valentina Tassinari , Piergiorgio La Rosa , Eugenia Guida , Ambra Colopi , Sara Caratelli , Francesca De Paolis , Angela Gallo , Carlo Cenciarelli , Giuseppe Sconocchia , Susanna Dolci , Valeriana Cesarini

{"title":"Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases","authors":"Valentina Tassinari , Piergiorgio La Rosa , Eugenia Guida , Ambra Colopi , Sara Caratelli , Francesca De Paolis , Angela Gallo , Carlo Cenciarelli , Giuseppe Sconocchia , Susanna Dolci , Valeriana Cesarini","doi":"10.1016/j.mad.2023.111807","DOIUrl":"10.1016/j.mad.2023.111807","url":null,"abstract":"<div><p>Aging is a physiological and progressive phenomenon in all organisms' life cycle, characterized by the accumulation of degenerative processes triggered by several alterations within molecular pathways. These changes compromise cell fate, resulting in the loss of functions in tissues throughout the body, including the brain. Physiological brain aging has been linked to structural and functional alterations, as well as to an increased risk of neurodegenerative diseases. Post-transcriptional RNA modifications modulate mRNA coding properties, stability, translatability, expanding the coding capacity of the genome, and are involved in all cellular processes. Among mRNA post-transcriptional modifications, the A-to-I RNA editing, m6A RNA Methylation and Alternative Splicing play a critical role in all the phases of a neuronal cell life cycle and alterations in their mechanisms of action significantly contribute to aging and neurodegeneration. Here we review our current understanding of the contribution of A-to-I RNA editing, m6A RNA Methylation, and Alternative Splicing to physiological brain aging process and neurodegenerative diseases.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965670","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}

引用次数: 4