Ageing Research Reviews最新文献

{"title":"The role of exercise in the prevention and treatment of Alzheimer’s disease and mild cognitive impairments","authors":"Calvin D. Brooks ,&nbsp;Raghu R. Krishnamoorthy ,&nbsp;Nathalie Sumien","doi":"10.1016/j.arr.2024.102555","DOIUrl":"10.1016/j.arr.2024.102555","url":null,"abstract":"<div><div>Large retrospective cohort studies have consistently shown that people who exercise regularly are at a markedly reduced risk of dementias such as Alzheimer’s Disease (AD). Animal studies have also found that exercise can prevent cognitive decline, and recent studies have identified possible mechanisms. However, randomized controlled trials of exercise interventions in AD and mild cognitive impairment have not reached a consensus regarding the efficacy of this treatment, hampering clinical adoption of this technique. This review examines these randomized controlled trials to assess potential causes for the variability in the measured outcomes. We posit that great variance in the methods used in these studies may account for some of the differences seen in outcomes. We determined that aerobic exercise led to the most benefits, that many cognitive domains improve with exercise, and that aerobic exercise enhances the ability for independent living. However, cognitive improvements were more pronounced and consistent in patients with mild cognitive impairment than AD, suggesting a narrow window of opportunity for exercise intervention.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102555"},"PeriodicalIF":12.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic biomarkers in Alzheimer's disease: Diagnostic and prognostic relevance","authors":"Tapan Behl ,&nbsp;Ashishkumar Kyada ,&nbsp;R. Roopashree ,&nbsp;Deepak Nathiya ,&nbsp;Renu Arya ,&nbsp;M. Ravi Kumar ,&nbsp;Mohammad Khalid ,&nbsp;Monica Gulati ,&nbsp;Monika Sachdeva ,&nbsp;Mohammad Fareed ,&nbsp;Pratap Kumar Patra ,&nbsp;Ankur Agrawal ,&nbsp;Pranay Wal ,&nbsp;Amin Gasmi","doi":"10.1016/j.arr.2024.102556","DOIUrl":"10.1016/j.arr.2024.102556","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a leading cause of cognitive decline in the aging population, presenting a critical need for early diagnosis and effective prognostic tools. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have emerged as promising biomarkers for AD due to their roles in regulating gene expression and potential for reversibility. This review examines the current landscape of epigenetic biomarkers in AD, emphasizing their diagnostic and prognostic relevance. DNA methylation patterns in genes such as APP, PSEN1, and PSEN2 are highlighted for their strong associations with AD pathology. Alterations in DNA methylation at specific CpG sites have been consistently observed in AD patients, suggesting their utility in early detection. Histone modifications, such as acetylation and methylation, also play a crucial role in chromatin remodelling and gene expression regulation in AD. Dysregulated histone acetylation and methylation have been linked to AD progression, making these modifications valuable biomarkers. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), further contribute to the epigenetic regulation in AD. miRNAs can modulate gene expression post-transcriptionally and have been found in altered levels in AD, while lncRNAs can influence chromatin structure and gene expression. The presence of these non-coding RNAs in biofluids like blood and cerebrospinal fluid positions them as accessible and minimally invasive biomarkers. Technological advancements in detecting and quantifying epigenetic modifications have propelled the field forward. Techniques such as next-generation sequencing, bisulfite sequencing, and chromatin immunoprecipitation assays offer high sensitivity and specificity, enabling the detailed analysis of epigenetic changes in clinical samples. These tools are instrumental in translating epigenetic research into clinical practice. This review underscores the potential of epigenetic biomarkers to enhance the early diagnosis and prognosis of AD, paving the way for personalized therapeutic strategies and improved patient outcomes. The integration of these biomarkers into clinical workflows promises to revolutionize AD management, offering hope for better disease monitoring and intervention.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102556"},"PeriodicalIF":12.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(Poly)phenols and diabetes: From effects to mechanisms by systematic multigenomic analysis","authors":"Maria Inês Farrim ,&nbsp;Andreia Gomes ,&nbsp;Regina Menezes ,&nbsp;Dragan Milenkovic","doi":"10.1016/j.arr.2024.102557","DOIUrl":"10.1016/j.arr.2024.102557","url":null,"abstract":"<div><div>Diabetes is a chronic and multifactorial metabolic disease with increasing numbers of patients worldwide, characterized by loss of pancreatic β-cell mass and function with subsequent insulin deficiency. Thus, restoring functional β-cells could significantly impact disease management. The beneficial effects of natural compounds, namely (poly)phenols, in diabetes have gained increasing interest, due to their pleiotropic actions in several cellular processes, including in glucose homeostasis. These compounds are able to modulate nutri(epi)genomic mechanisms by interacting with cell signaling proteins and transcription factors (TFs). However, the underlying mechanisms of action, particularly of (poly)phenol metabolites resulting from digestion and colonic microbiota action, are yet to be elucidated. This study explored the multigenomic effects of (poly)phenols and their metabolites to uncover modulatory networks and mechanisms linked to diabetes. Published studies on gene expression alterations modulated by (poly)phenolic compounds or (poly)phenol-rich extracts were integrated, encompassing studies conducted on individuals with diabetes, animal models mimicking diabetes, and pancreatic β-cell lines. Bioinformatic analysis identified differentially expressed genes and potential regulatory factors, with roles in cell signaling pathways (FoxO, AMPK, p53), endocrine resistance, immune system pathways, apoptosis, and cellular senescence. Interestingly, in silico 3D docking analyses revealed potential interactions between key TFs (FOXO1, PPARG, SIRT1, and MAFA) and some metabolites. Apigenin, luteolin, and naringenin glucuronide forms showed the best binding capacity to SIRT1. The integrative analysis of (poly)phenol metabolites data highlights the potential of these molecules for nutraceutical/pharmaceutical development aimed at managing diabetes whose incidence increases with age.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102557"},"PeriodicalIF":12.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of frailty screening instruments for older people in Sub-Saharan Africa: A scoping review","authors":"Gideon Dzando ,&nbsp;Paul R. Ward ,&nbsp;Dennis Asante ,&nbsp;Rachel C. Ambagtsheer","doi":"10.1016/j.arr.2024.102571","DOIUrl":"10.1016/j.arr.2024.102571","url":null,"abstract":"<div><h3>Background</h3><div>Frailty and frailty screening of older people is increasingly becoming a global public health concern. The health domains and elements that constitute frailty may differ across different settings. The choice of frailty screening instruments can therefore affect frailty diagnosis and potentially delay interventions. The aim of this scoping review is to explore the application of frailty screening instruments among older people in Sub-Saharan Africa.</div></div><div><h3>Method</h3><div>Six databases (Google Scholar, CINAHL, SCOPUS, African Journal online, PubMed, and Africa Index Medicus) were searched for literature published between January 2000 and August 2023. Studies that reported on using frailty screening instruments for older people aged 50 years and above in Sub-Saharan Africa were included in the review.</div></div><div><h3>Results</h3><div>The search across the six databases yielded 362 results. Seventeen studies from ten countries met the eligibility criteria and were included in this review. Seven frailty screening instruments were identified across the included studies. Frailty screening is gaining attention in Sub-Saharan Africa. Majority of the frailty screening instruments were developed and validated in high-income countries. Only one frailty screening instrument was developed and validated in Sub-Saharan Africa.</div></div><div><h3>Conclusion</h3><div>Considering the impact of frailty on the health and wellbeing of older people, researchers must consider developing and using frailty screening instruments that assess domains that are pertinent to the health and wellbeing of older people in Sub-Saharan Africa.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102571"},"PeriodicalIF":12.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing insights into the transcriptional landscape of Parkinson's disease","authors":"Yun Su ,&nbsp;Huimin Zheng ,&nbsp;Xin Cui ,&nbsp;Shuyu Zhang ,&nbsp;Shuo Zhang ,&nbsp;Zhengwei Hu ,&nbsp;Xiaoyan Hao ,&nbsp;Mengjie Li ,&nbsp;Guangyu Guo ,&nbsp;Zongping Xia ,&nbsp;Changhe Shi ,&nbsp;Chengyuan Mao ,&nbsp;Yuming Xu","doi":"10.1016/j.arr.2024.102553","DOIUrl":"10.1016/j.arr.2024.102553","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, with an unknown etiology and no specific treatment. Emerging single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have become instrumental in unravelling cellular heterogeneity and characterizing molecular signatures at single-cell resolution. Single-cell T cell receptor sequencing (scTCR-seq) and single-cell B cell receptor sequencing (scBCR-seq) technologies provide unprecedented opportunities to explore the immune repertoire diversity. These state-of-the-art technologies have been increasingly applied in PD research in the last five years, offering novel insights into the cellular susceptibilities and complex molecular mechanisms underlying PD pathogenesis. Herein we review recent advances in the applications of sc/snRNA-seq, scTCR-seq and scBCR-seq technologies in various PD models. Moreover, we focus on degenerative neurons, activated neuroglial cells, as well as pro-inflammatory immune cells, exploring their unique transcriptional landscapes in PD, as revealed by single-cell sequencing technologies. Finally, we highlight important challenges and the future directions of single-cell experiments in PD research.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102553"},"PeriodicalIF":12.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mGluR7: The new player protecting the central nervous system","authors":"Pan Li ,&nbsp;Wangrui Lei ,&nbsp;Yushu Dong ,&nbsp;Xiaowu Wang ,&nbsp;Xingyan Ye ,&nbsp;Ye Tian ,&nbsp;Yaru Yang ,&nbsp;Jie Liu ,&nbsp;Ning Li ,&nbsp;Xiaochen Niu ,&nbsp;Xin Wang ,&nbsp;Yifan Tian ,&nbsp;Lu Xu ,&nbsp;Yang Yang ,&nbsp;Jincheng Liu","doi":"10.1016/j.arr.2024.102554","DOIUrl":"10.1016/j.arr.2024.102554","url":null,"abstract":"<div><div>Metabotropic glutamate receptor 7 (mGluR7) belongs to the family of type III mGluR receptor, playing an important part in the central nervous system (CNS) through response to neurotransmitter regulation, reduction of excitatory toxicity, and early neuronal development. Drugs targeting mGluR7 (mGluR7 agonists, antagonists, and allosteric modulators) may be among the most promising agents for the treatment of CNS disorders, such as psychiatric disorders, neurodegenerative diseases, and neurodevelopmental impairments, though these potential therapies are at early stages and the data are still limited. In this review, we summarized the structure and function of mGluR7 and discussed recent progress on mGluR7 agonists and antagonists. A deeper understanding of mGluR7 will contribute to uncovering the molecular mechanisms of neuroprotection and providing a theoretical basis for the formulation of therapeutic strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102554"},"PeriodicalIF":12.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress and cell senescence as drivers of ageing: Chicken and egg","authors":"Thomas von Zglinicki","doi":"10.1016/j.arr.2024.102558","DOIUrl":"10.1016/j.arr.2024.102558","url":null,"abstract":"<div><div>Oxidative stress and cell senescence are both important drivers of ageing and age-associated disease and disability. In vitro, they are closely interconnected in a chicken-and-egg relationship: Not only is oxidative stress an important cause of cell senescence, but senescent cells are also sources of oxidative stress, obscuring cause-effect relationships during the ageing process. We hypothesize that cell senescence is a significant cause of tissue and systemic oxidative stress during ageing. This review aims to critically summarize the available evidence for this hypothesis. After summarizing the cellular feedback mechanisms that make oxidative stress an integral part of the senescent phenotype, it critically reviews the existing evidence for a role of senescent cells as causes of oxidative stress during mammalian ageing in vivo, focussing on results from intervention experiments. It is concluded that while the available data are in agreement with this hypothesis, they are still too scarce to support a robust conclusion.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102558"},"PeriodicalIF":12.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of hypoxia-inducible factor-prolyl hydroxylases in aging and disease","authors":"Fedor Galkin ,&nbsp;Fadi E. Pulous ,&nbsp;Yanyun Fu ,&nbsp;Man Zhang ,&nbsp;Frank W. Pun ,&nbsp;Feng Ren ,&nbsp;Alex Zhavoronkov","doi":"10.1016/j.arr.2024.102551","DOIUrl":"10.1016/j.arr.2024.102551","url":null,"abstract":"<div><div>The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on hypoxia, there is a growing recognition of its importance under normoxic conditions. Recent advances in PHD biology have highlighted the potential of targeting this pathway therapeutically for a range of aging-related diseases. In this article, we review these recent discoveries, situate them within the broader context of aging and disease, and explore current therapeutic strategies that target PHD enzymes for these indications.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102551"},"PeriodicalIF":12.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions","authors":"Luigi Ferrucci ,&nbsp;Flora Guerra ,&nbsp;Cecilia Bucci ,&nbsp;Emanuele Marzetti ,&nbsp;Anna Picca","doi":"10.1016/j.arr.2024.102549","DOIUrl":"10.1016/j.arr.2024.102549","url":null,"abstract":"<div><div>Mitophagy is the intracellular recycling system that disposes damaged/inefficient mitochondria and allows biogenesis of new organelles to ensure mitochondrial quality is optimized. Dysfunctional mitophagy has been implicated in human aging and diseases. Multiple evolutionarily selected, redundant mechanisms of mitophagy have been identified, but their specific roles in human health and their potential exploitation as therapeutic targets are unclear. Recently, the characterization of the endosomal−lysosomal system has revealed additional mechanisms of mitophagy and mitochondrial quality control that operate via the production of mitochondria-derived vesicles (MDVs). Circulating MDVs can be isolated and characterized to provide an unprecedented opportunity to study this type of mitochondrial recycling <em>in vivo</em> and to relate it to human physiology and pathology. Defining the role of MDVs in human physiology, pathology, and aging is hampered by the lack of standardized methods to isolate, validate, and characterize these vesicles. Hence, some basic questions about MDVs remain unanswered. While MDVs are generated directly through the extrusion of mitochondrial membranes within the cell, a set of circulating extracellular vesicles leaking from the endosomal−lysosomal system and containing mitochondrial portions have also been identified and warrant investigation. Preliminary research indicates that MDV generation serves multiple biological roles and contributes to restoring cell homeostasis. However, studies have shown that MDVs may also be involved in pathological conditions. Therefore, further research is warranted to establish when/whether MDVs are supporting disease progression and/or are extracting damaged mitochondrial components to alleviate cellular oxidative burden and restore redox homeoastasis. This information will be relevant for exploiting these vesicles for therapeutic purpose. Herein, we provide an overview of preclinical and clinical studies on MDVs in aging and associated conditions and discuss the interplay between MDVs and some of the hallmarks of aging (mitophagy, inflammation, and proteostasis). We also outline open questions on MDV research that should be prioritized by future investigations.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102549"},"PeriodicalIF":12.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rodent model intervention for prevention and optimal management of sarcopenia: A systematic review on the beneficial effects of nutrients & non-nutrients and exercise to improve skeletal muscle health","authors":"Vijayakumar Mayakrishnan ,&nbsp;Priya Kannappan ,&nbsp;Janani Balakarthikeyan ,&nbsp;Choon Young Kim","doi":"10.1016/j.arr.2024.102543","DOIUrl":"10.1016/j.arr.2024.102543","url":null,"abstract":"<div><div>Sarcopenia is a common musculoskeletal disorder characterized by degenerative processes and is strongly linked to an increased susceptibility to falls, fractures, physical limitations, and mortality. Several models have been used to explore therapeutic and preventative measures as well as to gain insight into the molecular mechanisms behind sarcopenia. With novel experimental methodologies emerging to design foods or novel versions of conventional foods, understanding the impact of nutrition on the prevention and management of sarcopenia has become important. This review provides a thorough assessment of the use of rodent models of sarcopenia for understanding the aging process, focusing the effects of nutrients, plant extracts, exercise, and combined interventions on skeletal muscle health. According to empirical research, nutraceuticals and functional foods have demonstrated potential benefits in enhancing physical performance. In preclinical investigations, the administration of herbal extracts and naturally occurring bioactive compounds yielded advantageous outcomes such as augmented muscle mass and strength generation. Furthermore, herbal treatments exhibited inhibitory effects on muscle atrophy and sarcopenia. A substantial body of information establishes a connection between diet and the muscle mass, strength, and functionality of older individuals. This suggests that nutrition has a major impact in both the prevention and treatment of sarcopenia.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102543"},"PeriodicalIF":12.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}