NPJ Aging and Mechanisms of Disease最新文献

{"title":"Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.","authors":"Naoyuki Ishida,&nbsp;Yuichi Ishihara,&nbsp;Kazuto Ishida,&nbsp;Hiroyuki Tada,&nbsp;Yoshiko Funaki-Kato,&nbsp;Makoto Hagiwara,&nbsp;Taslima Ferdous,&nbsp;Mohammad Abdullah,&nbsp;Akio Mitani,&nbsp;Makoto Michikawa,&nbsp;Kenji Matsushita","doi":"10.1038/s41514-017-0015-x","DOIUrl":"https://doi.org/10.1038/s41514-017-0015-x","url":null,"abstract":"<p><p>Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as <i>Porphyromonas gingivalis</i>. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by <i>P. gingivalis</i> modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of <i>P. gingivalis</i>-inoculated mice. <i>P. gingivalis</i> LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by <i>P. gingivalis</i> may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0015-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35608125","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":"Somatic growth, aging, and longevity.","authors":"Andrzej Bartke","doi":"10.1038/s41514-017-0014-y","DOIUrl":"https://doi.org/10.1038/s41514-017-0014-y","url":null,"abstract":"<p><p>Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various \"pro-aging\" effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2017-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0014-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35566053","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":"Treatment of diabetic mice with the SGLT2 inhibitor TA-1887 antagonizes diabetic cachexia and decreases mortality.","authors":"Taichi Sugizaki,&nbsp;Shunshun Zhu,&nbsp;Ge Guo,&nbsp;Akiko Matsumoto,&nbsp;Jiabin Zhao,&nbsp;Motoyoshi Endo,&nbsp;Haruki Horiguchi,&nbsp;Jun Morinaga,&nbsp;Zhe Tian,&nbsp;Tsuyoshi Kadomatsu,&nbsp;Keishi Miyata,&nbsp;Hiroshi Itoh,&nbsp;Yuichi Oike","doi":"10.1038/s41514-017-0012-0","DOIUrl":"https://doi.org/10.1038/s41514-017-0012-0","url":null,"abstract":"<p><p>A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic <i>db/db</i> mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice. We also compare effects of SGLT2i TA-1887 with those of lowering blood glucose levels via insulin treatment. Untreated <i>db/db</i> mice showed remarkable weight loss, or cachexia, while TA-1887-treated mice did not but rather continued to gain weight at later time points and decreased mortality. TA-1887 treatment prevented pancreatic beta cell death, enhanced preservation of beta cell mass and endogenous insulin secretion, and increased insulin sensitivity. Moreover, TA-1887 treatment attenuated inflammation, oxidative stress, and cellular senescence, especially in visceral white adipose tissue, and antagonized endothelial dysfunction. Insulin treatment of <i>db/db</i> mice also prevented weight loss and antagonized inflammation and oxidative stress. However, insulin treatment had less potent effects on survival and prevention of cellular senescence and endothelial dysfunction than did TA-1887 treatment. SGLT2i treatment prevents diabetic cachexia and death by preserving function of beta cells and insulin target organs and attenuating complications. SGLT2i treatment may be a promising therapeutic strategy for type 2 diabetes patients with morbid obesity and severe insulin resistance.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2017-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0012-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35345992","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":"SMARCD1 regulates senescence-associated lipid accumulation in hepatocytes.","authors":"Chisato Inoue,&nbsp;Chong Zhao,&nbsp;Yumi Tsuduki,&nbsp;Miyako Udono,&nbsp;Lixiang Wang,&nbsp;Masatoshi Nomura,&nbsp;Yoshinori Katakura","doi":"10.1038/s41514-017-0011-1","DOIUrl":"https://doi.org/10.1038/s41514-017-0011-1","url":null,"abstract":"<p><p>Previously, we have identified 16 senescence-associated genes by a subtractive proteomic analysis using presenescent and senescent human fibroblast cells, TIG-1. The aim of this study was to clarify the role of SMARCD1, one of the identified genes, also known as BAF60a, in hepatic senescence. SMARCD1 is a member of the SWI/SNF chromatin remodeling complex family, and regulates the transcription of target genes through the alterations of chromatin structure. We demonstrated that the reduced expression of SMARCD1 triggers cellular senescence and induces the accumulation of lipids, suggesting that SMARCD1 acts as a mediator in these processes. Furthermore, palmitic acid treatment and high-fat diet led to a significant reduction of SMARCD1 expression, and consequently induced cellular senescence and lipid accumulation in HepG2 cells and mouse liver, respectively. The results obtained here suggest that dietary nutrient-associated impaired expression of SMARCD1 triggers cellular senescence and lipid accumulation, indicating a potential application of SMARCD1 in the prevention of lifestyle-related diseases.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2017-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0011-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35322234","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":"Erratum: Ubiquitous overexpression of the DNA repair factor <i>dPrp19</i> reduces DNA damage and extends <i>Drosophila</i> life span.","authors":"Kathrin Garschall,&nbsp;Hanna Dellago,&nbsp;Martina Gáliková,&nbsp;Markus Schosserer,&nbsp;Thomas Flatt,&nbsp;Johannes Grillari","doi":"10.1038/s41514-017-0008-9","DOIUrl":"https://doi.org/10.1038/s41514-017-0008-9","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1038/s41514-017-0005-z.].</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2017-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0008-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35608124","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":"Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies.","authors":"Megumi Hatori,&nbsp;Claude Gronfier,&nbsp;Russell N Van Gelder,&nbsp;Paul S Bernstein,&nbsp;Josep Carreras,&nbsp;Satchidananda Panda,&nbsp;Frederick Marks,&nbsp;David Sliney,&nbsp;Charles E Hunt,&nbsp;Tsuyoshi Hirota,&nbsp;Toshiharu Furukawa,&nbsp;Kazuo Tsubota","doi":"10.1038/s41514-017-0010-2","DOIUrl":"https://doi.org/10.1038/s41514-017-0010-2","url":null,"abstract":"<p><p>Mammals receive light information through the eyes, which perform two major functions: image forming vision to see objects and non-image forming adaptation of physiology and behavior to light. Cone and rod photoreceptors form images and send the information via retinal ganglion cells to the brain for image reconstruction. In contrast, nonimage-forming photoresponses vary widely from adjustment of pupil diameter to adaptation of the circadian clock. nonimage-forming responses are mediated by retinal ganglion cells expressing the photopigment melanopsin. Melanopsin-expressing cells constitute 1-2% of retinal ganglion cells in the adult mammalian retina, are intrinsically photosensitive, and integrate photic information from rods and cones to control nonimage-forming adaptation. Action spectra of ipRGCs and of melanopsin photopigment peak around 480 nm blue light. Understanding melanopsin function lets us recognize considerable physiological effects of blue light, which is increasingly important in our modern society that uses light-emitting diode. Misalignment of circadian rhythmicity is observed in numerous conditions, including aging, and is thought to be involved in the development of age-related disorders, such as depression, diabetes, hypertension, obesity, and cancer. The appropriate regulation of circadian rhythmicity by proper lighting is therefore essential. This perspective introduces the potential risks of excessive blue light for human health through circadian rhythm disruption and sleep deprivation. Knowing the positive and negative aspects, this study claims the importance of being exposed to light at optimal times and intensities during the day, based on the concept of the circadian clock, ultimately to improve quality of life to have a healthy and longer life.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2017-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0010-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35118559","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":"Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.","authors":"Evi M Mercken,&nbsp;Miriam Capri,&nbsp;Bethany A Carboneau,&nbsp;Maria Conte,&nbsp;Juliana Heidler,&nbsp;Aurelia Santoro,&nbsp;Alejandro Martin-Montalvo,&nbsp;Marta Gonzalez-Freire,&nbsp;Husam Khraiwesh,&nbsp;José A González-Reyes,&nbsp;Ruin Moaddel,&nbsp;Yongqing Zhang,&nbsp;Kevin G Becker,&nbsp;José M Villalba,&nbsp;Julie A Mattison,&nbsp;Ilka Wittig,&nbsp;Claudio Franceschi,&nbsp;Rafael de Cabo","doi":"10.1038/s41514-017-0009-8","DOIUrl":"https://doi.org/10.1038/s41514-017-0009-8","url":null,"abstract":"<p><p>Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species. Two downregulated pathways, the electron transport chain and oxidative phosphorylation, were common among all four species in response to aging. Quantitative PCR, biochemical analysis, mitochondrial DNA measurements, and electron microscopy revealed a conserved age-dependent decrease in mitochondrial content, and a reduction in oxidative phosphorylation complexes in monkeys and humans. Western blot analysis of key proteins in mitochondrial biogenesis discovered that (i) an imbalance toward mitochondrial fusion occurs in aged skeletal muscle and (ii) mitophagy is not overtly affected, presumably leading to the observed accumulation of abnormally large, damaged mitochondria with age. Select transcript expression analysis uncovered that the skeletal inflammatory profile differentially increases with age, but is most pronounced in humans, while increased oxidative stress (as assessed by protein carbonyl adducts and 4-hydroxynonenal) is common among all species. Expression studies also found that there is unique dysregulation of the nutrient sensing pathways among the different species with age. The identification of conserved pathways indicates common molecular mechanisms intrinsic to health and lifespan, whereas the recognition of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0009-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35118558","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":"Opposing activities of oncogenic MIR17HG and tumor suppressive MIR100HG clusters and their gene targets regulate replicative senescence in human adult stem cells.","authors":"Mary F Lopez,&nbsp;Ping Niu,&nbsp;Lu Wang,&nbsp;Maryann Vogelsang,&nbsp;Meenakshi Gaur,&nbsp;Bryan Krastins,&nbsp;Yueqiang Zhao,&nbsp;Aibek Smagul,&nbsp;Aliya Nussupbekova,&nbsp;Aikan A Akanov,&nbsp;I King Jordan,&nbsp;Victoria V Lunyak","doi":"10.1038/s41514-017-0006-y","DOIUrl":"https://doi.org/10.1038/s41514-017-0006-y","url":null,"abstract":"<p><p>Growing evidence suggests that many diseases of aging, including diseases associated with robust changes and adipose deports, may be caused by resident adult stem cell exhaustion due to the process called cellular senescence. Understanding how microRNA pathways can regulate cellular senescence is crucial for the development of novel diagnostic and therapeutic strategies to combat these pathologies. Herein, using integrated transcriptomic and semi-quantitative proteomic analysis, we provide a system level view of the regulation of human adipose-derived stem cell senescence by a subset of mature microRNAs (termed senescence-associated-microRNAs) produced by biogenesis of oncogenic <i>MIR17HG</i> and tumor-suppressive <i>MIR100HG</i> clusters. We demonstrate functional significance of these mature senescence-associated-microRNAs in the process of replicative senescence of human adipose-derived stem cells ex-vivo and define a set of senescence-associated-microRNA gene targets that are able to elicit, modulate and, most importantly, balance intimate connections between oncogenic and senescent events.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2017-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0006-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35118557","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":"An alanine expanded PABPN1 causes increased utilization of intronic polyadenylation sites.","authors":"Tooba Abbassi-Daloii,&nbsp;Soheil Yousefi,&nbsp;Eleonora de Klerk,&nbsp;Laurens Grossouw,&nbsp;Muhammad Riaz,&nbsp;Peter A C 't Hoen,&nbsp;Vered Raz","doi":"10.1038/s41514-017-0007-x","DOIUrl":"https://doi.org/10.1038/s41514-017-0007-x","url":null,"abstract":"<p><p>In eukaryote genomes, the polyadenylation site marks termination of mature RNA transcripts by a poly-adenine tail. The polyadenylation site is recognized by a dynamic protein complex, among which the poly-adenine-binding protein nuclear1 plays a key role. Reduced poly-adenine-binding protein nuclear1 levels are found in aged muscles and are even lower in oculopharyngeal muscular dystrophy patients. Oculopharyngeal muscular dystrophy is a rare, late onset autosomal dominant myopathy, and is caused by an alanine expansion mutation in poly-adenine-binding protein nuclear1. Mutant poly-adenine-binding protein nuclear1 forms insoluble nuclear aggregates leading to depletion of functional poly-adenine-binding protein nuclear1 levels. In oculopharyngeal muscular dystrophy models, increased utilization of proximal polyadenylation sites has been observed in tandem 3'-untranslated regions, and most often cause gene upregulation. However, global alterations in expression profiles canonly partly be explained by polyadenylation site switches within the most distal 3'-untranslated region. Most poly-adenine signals are found at the distal 3'-untranslated region, but a significant part is also found in internal gene regions, like introns, exons, and internal 3'-untranslated regions. Here, we investigated poly-adenine-binding protein nuclear1's role in polyadenylation site utilization in internal gene regions. In the quadriceps muscle of oculopharyngeal muscular dystrophy mice expressing expPABPN1 we found significant polyadenylation site switches between gene regions in 17% of genes with polyadenylation site in multiple regions (<i>N</i> = 574; 5% False Discovery Rate). Polyadenylation site switches between gene regions were associated with differences in transcript expression levels and alterations in open reading frames. Transcripts ending at internal polyadenylation site were confirmed in tibialis anterior muscles from the same mice and in mouse muscle cell cultures overexpressing expPABPN1. The polyadenylation site switches were associated with nuclear accumulation of full-length transcripts. Our results provide further insights into the diverse roles of poly-adenine-binding protein nuclear1 in the post-transcriptional control of muscle gene expression and its relevance for oculopharyngeal muscular dystrophy pathology and muscle aging.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2017-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0007-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35118556","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":"Both overlapping and independent mechanisms determine how diet and insulin-ligand knockouts extend lifespan of <i>Drosophila melanogaster</i>.","authors":"Jelle Zandveld,&nbsp;Joost van den Heuvel,&nbsp;Bastiaan J Zwaan,&nbsp;Matthew D W Piper","doi":"10.1038/s41514-017-0004-0","DOIUrl":"https://doi.org/10.1038/s41514-017-0004-0","url":null,"abstract":"<p><p>Lifespan in many organisms, including <i>Drosophila melanogaster</i>, can be increased by reduced insulin-IGF-like signaling (IIS) or by changes in diet. Most studies testing whether IIS is involved in diet-mediated lifespan extension employ only a few diets, but recent data shows that a broad range of nutritional environments is required. Here, we present lifespan data of long-lived <i>Drosophila</i>, lacking three of the eight insulin-like peptides [<i>Drosophila</i> insulin-like peptides 2,3,5 (<i>dilp2-3,5</i>)] on nine different diets that surround the optimum for lifespan. Their nutritional content was varied by manipulating sugar and yeast concentrations independently, and thus incorporated changes in both diet restriction and nutrient balance. The mutants were substantially longer-lived than controls on every diet, but the effects on the lifespan response to sugar and yeast differed. Our data illustrates how a greater coverage of diet balance (DB) and restriction can unify differing interpretations of how IIS might be involved in the response of lifespan to diet.</p>","PeriodicalId":19334,"journal":{"name":"NPJ Aging and Mechanisms of Disease","volume":" ","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2017-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-017-0004-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35118554","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}