Yilin Chen , Juan I. Bravo , Jyung Mean Son , Changhan Lee , Bérénice A. Benayoun
{"title":"Remodeling of the H3 nucleosomal landscape during mouse aging","authors":"Yilin Chen , Juan I. Bravo , Jyung Mean Son , Changhan Lee , Bérénice A. Benayoun","doi":"10.1016/j.tma.2019.12.003","DOIUrl":"10.1016/j.tma.2019.12.003","url":null,"abstract":"<div><p>In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (<em>i.e.</em> the ‘epigenome’) can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, although alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mouse tissues (<em>i.e.</em> heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs during aging.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 22-31"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2019.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37983094","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}
{"title":"Integration of immune-metabolic signals to preserve healthy aging","authors":"Emily L. Goldberg","doi":"10.1016/j.tma.2020.07.005","DOIUrl":"10.1016/j.tma.2020.07.005","url":null,"abstract":"<div><p>Inflammation is a broad term that refers to a collection of carefully balanced programs in the body. These pathways are essential for detecting invading microorganisms, controlling the spread of infection, and instructing appropriate immune responses to eliminate pathogens. During aging there is deterioration of important regulatory mechanisms, giving rise to persistent low-grade inflammation that drives chronic conditions such as metabolic dysregulation, immune senescence, and cognitive decline. Understanding this aspect of the pathobiology of aging is key to uncovering the source(s) and cause(s) of age-related inflammation that underlies disease.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 93-95"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25414947","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}
Ana R. Silverstein, Melanie K. Flores, Brendan Miller, Su-Jeong Kim, Kelvin Yen, Hemal H. Mehta, Pinchas Cohen
{"title":"Mito-Omics and immune function: Applying novel mitochondrial omic techniques to the context of the aging immune system","authors":"Ana R. Silverstein, Melanie K. Flores, Brendan Miller, Su-Jeong Kim, Kelvin Yen, Hemal H. Mehta, Pinchas Cohen","doi":"10.1016/j.tma.2020.08.001","DOIUrl":"10.1016/j.tma.2020.08.001","url":null,"abstract":"<div><p>Recent advancements in genomic, transcriptomic, proteomic, and metabolomic techniques have prompted fresh inquiry in the field of aging. Here, we outline the application of these techniques in the context of the mitochondrial genome and suggest their potential for use in exploring the biological mechanisms of the aging immune system.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 132-140"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38308421","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}
{"title":"Extracellular vesicles and extracellular RNA in aging and age-related disease","authors":"Nicole Noren Hooten Ph.D.","doi":"10.1016/j.tma.2020.07.006","DOIUrl":"10.1016/j.tma.2020.07.006","url":null,"abstract":"<div><p>Circulating factors are well known to influence aging and age-related disease. As part of the Aging Science Talks: Science for the Community series, data was presented on two types of circulating functional biomarkers: extracellular RNA (exRNA) and extracellular vesicles (EVs). EVs in the context of type 2 diabetes mellitus was also discussed, as this is an area of interest due to the growing global epidemic of this age-related disease.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 96-98"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.07.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38444642","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}
{"title":"Improving trainee engagement in science: Lessons from a virtual seminar series","authors":"Hannah J. Smith","doi":"10.1016/j.tma.2020.06.003","DOIUrl":"10.1016/j.tma.2020.06.003","url":null,"abstract":"<div><p>To be a successful researcher, you are expected to have important skills beyond the bench such as being able to ask questions, talk about science with your peers, and organize scientific events. However, there is frequently little to no training or emphasis on these skills at the student and postdoc level. The virtual Aging Science Talks seminar series and Slack group have benefitted the scientific community in many ways amidst the chaos of coronavirus quarantines and lab shutdowns, but as a 2<sup>nd</sup> year PhD student, I was particularly excited about how this format was able to engage trainees. We should end the era of trainees sitting at the back of the room while PIs dominate discussions and Q&A sessions with speakers. Reflecting on the advantages of Aging Science Talks can show us how to make future scientific events more engaging and inclusive for everyone.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 76-77"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38654310","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}
Daniel P. Felker , Christine E. Robbins , Mark A. McCormick
{"title":"Automation of C. elegans lifespan measurement","authors":"Daniel P. Felker , Christine E. Robbins , Mark A. McCormick","doi":"10.1016/j.tma.2019.12.001","DOIUrl":"10.1016/j.tma.2019.12.001","url":null,"abstract":"<div><p>Aging is a fundamental biological process that is still not fully understood. As many of the most significant human diseases have aging as their greatest risk factor, a better understanding of aging potentially has enormous practical implications in treating these diseases. The nematode <em>C. elegans</em> is an exceptionally useful genetic model organism that had been used with great success to shed light on many genes and pathways that are involved in aging. Many of these pathways and mechanisms have been shown to be conserved through mammals. The standard methods for assaying survival in <em>C. elegans</em> to measure changes in lifespan are tedious and time consuming. This limits the throughput and productivity of <em>C. elegans</em> aging researchers. In recent years, many inroads have been made into automating various facets of the collection and analysis of <em>C. elegans</em> lifespan experimental data. The advances described in this review all work to ameliorate some of the hurdles that come with manual worm lifespan scoring, by automating or eliminating some of the most time consuming aspects of the assay. By greatly increasing the throughput of lifespan assays, these methods will enable types of experiments (e.g., drug library screens) whose scale is currently impractical. These methods have already proved exceptionally useful, and some of them are likely to be the predecessors of even more refined methods that could lead to breakthroughs in the ability to study lifespan in <em>C. elegans</em>. This could in turn potentially revolutionize our understanding of the basic biology of aging, and one day lead to treatments that could offset or delay age-related diseases in humans.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 1-10"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2019.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55175693","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}
Takashi K. Ito , Tomohito Sato , Akio Hakamata , Yuki Onoda , Shumpei Sato , Fumiyoshi Yamazaki , Makoto Horikawa , Yutaka Takahashi , Takuya Kitamoto , Masako Suzuki , Shinya Uchida , Keiichi Odagiri , Mitsutoshi Setou
{"title":"A nonrandomized study of single oral supplementation within the daily tolerable upper level of nicotinamide affects blood nicotinamide and NAD+ levels in healthy subjects","authors":"Takashi K. Ito , Tomohito Sato , Akio Hakamata , Yuki Onoda , Shumpei Sato , Fumiyoshi Yamazaki , Makoto Horikawa , Yutaka Takahashi , Takuya Kitamoto , Masako Suzuki , Shinya Uchida , Keiichi Odagiri , Mitsutoshi Setou","doi":"10.1016/j.tma.2020.04.002","DOIUrl":"10.1016/j.tma.2020.04.002","url":null,"abstract":"<div><p>A decrease in nicotinamide adenine dinucleotide (NAD<sup>+</sup>) levels is a hallmark of aging in multiple organisms, including humans. We report a human clinical trial designed to assess the efficacy of single-dose supplementation of nicotinamide, a form of vitamin B3, on increasing NAD<sup>+</sup> levels. Nicotinamide intake within the daily tolerable upper level (200 mg) led to the maximal whole blood concentration by a 30-fold increase at 0.5 h with a consistent decrease until 6 h in all 6 healthy male volunteers. The increase in blood nicotinamide amounted to 17%, whereas renal clearance accounted for 1.8% of the ingested dose. NAD<sup>+</sup> levels reached a maximum concentration at 12 h, with all time points showing a trend of increase. Blood metabolome assay indicates that the metabolomic changes with NAM supplementation lasted 24 h and then returned to baseline by 48 h. The basal levels of whole blood NAD<sup>+</sup> varied among individuals with a negative correlation with body height as well as nicotinamide mononucleotide (NMN) levels. These data warrant consideration for further clinical evaluation with repeated doses of nicotinamide within the safety dose range for the potency to increase NAD<sup>+</sup> levels and potential accompanying benefits for healthy longevity.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 45-54"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.04.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55175751","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}
Minwook Kim , Daniela Knoefler , Ellen Quarles , Ursula Jakob , Daphne Bazopoulou
{"title":"Automated phenotyping and lifespan assessment of a C. elegans model of Parkinson’s disease","authors":"Minwook Kim , Daniela Knoefler , Ellen Quarles , Ursula Jakob , Daphne Bazopoulou","doi":"10.1016/j.tma.2020.04.001","DOIUrl":"10.1016/j.tma.2020.04.001","url":null,"abstract":"<div><p>Phenotypic analysis of <em>Caenorhabditis elegans</em> has greatly advanced our understanding of the molecular mechanisms implicated in the aging process as well as in age-related pathologies. However, conventional high-resolution imaging methods and survival assays are labor-intensive and subject to operator-based variations and decreased reproducibility. Recent advances in microfluidics and automated flatbed scanner technologies have significantly improved experimentation by eliminating handling errors and increasing the sensitivity in measurements. Here, we introduce a medium-throughput microfluidic platform, which efficiently positions and immobilizes single worms through pressurization for high resolution imaging. Worms are sorted based on select imaging criteria, and subsequently transferred into multi-well plates for automated lifespan assessment. To illustrate the applicability of this method, we imaged α-synuclein deposits in a <em>C. elegans</em> model of Parkinson’s Disease (PD). We found that age synchronized individuals expressing human α-synuclein vary greatly in the quantity and size of intracellular α-synuclein foci at early stages in life. Subsequent lifespan analysis of the individuals, however, did not reveal any correlation between the number or extent of α-synuclein deposits and subsequent lifespan. These studies suggest that the observed natural variations in α-synuclein deposits found in <em>C. elegans</em> models of PD do not originate from inherent differences in the fitness of the organism or contribute to alterations in lifespan.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 38-44"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25355378","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}
{"title":"Introduction: Special issue on Aging Science Talks: Science for our community during isolation","authors":"Dudley W. Lamming, Christy S. Carter","doi":"10.1016/j.tma.2020.09.001","DOIUrl":"10.1016/j.tma.2020.09.001","url":null,"abstract":"","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"4 ","pages":"Pages 149-150"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tma.2020.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38377204","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}