A database of vertebrate longevity records and their relation to other life‐history traits

Longevity is a major characteristic of animals that has long fascinated scientists. In this work, we present a comprehensive database of animal longevity records and related life‐history traits entitled AnAge, which we compiled and manually curated from an extensive literature. AnAge started as a collection of longevity records, but has since been expanded to include quantitative data for numerous other life‐history traits, including body masses at different developmental stages, reproductive data such as age at sexual maturity and measurements of reproductive output, and physiological traits related to metabolism. AnAge features over 4000 vertebrate species and is a central resource for applying the comparative method to studies of longevity and life‐history evolution across the tree of life. Moreover, by providing a reference value for longevity and other life‐history traits, AnAge can prove valuable to a broad range of biologists working in evolutionary biology, ecology, zoology, physiology and conservation biology. AnAge is freely available online ( http://genomics.senescence.info/species/ ).     

The DrugAge database of aging‐related drugs

Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge ( http://genomics.senescence.info/drugs/ ), a curated database of lifespan‐extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug–gene interaction data, we also performed a functional enrichment analysis of targets of lifespan‐extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan‐extending drugs and known aging‐related genes, suggesting that some but not most aging‐related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists.     

Shortest-Path Network Analysis Is a Useful Approach toward Identifying Genetic Determinants of Longevity

Background

Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking.

Methodology/Principal Findings

We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein–protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction.

Conclusions/Significance

This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of network analysis of aging to be extensively validated in a biological system. The novel longevity genes identified in this study are likely to yield further insight into the molecular mechanisms of aging and age-associated disease.     

Books for free? How can this be?— A PubMed resource you may be overlooking

The NCBI (National Center for Biotechnology Information) at the National Institutes of Health collects a wide range of molecular biological data, and develops tools and databases to analyse and disseminate this information. Many life scientists are familiar with the website maintained by the NCBI (http://www.ncbi.nlm.nih.gov), because they use it to search GenBank for homologues of their genes of interest or to search the PubMed database for scientific literature of interest. There is also a database called the Bookshelf that includes searchable popular life science textbooks, medical and research reference books and NCBI reference materials. The Bookshelf can be useful for researchers and educators to find basic biological information. This article includes a representative list of the resources currently available on the Bookshelf, as well as instructions on how to access the information in these resources.     

Longevity genomics across species

Unbiased genome-wide studies of longevity in S. cerevisiae and C. elegans have led to the identification of more than one hundred genes that determine life span in one or both organisms. Key pathways have been uncovered linking nutrient and growth factor cues to longevity. Quantitative measures of the degree to which aging is evolutionary conserved are now possible. A major challenge for the future is determining which of these genes play a similar role in human aging and using that information to develop therapies toward age-associated diseases.     

Human longevity: Genetics or Lifestyle? It takes two to tango

Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging.On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity.     

Genes, Demography, and Life Span: The Contribution of Demographic Data in Genetic Studies on Aging and Longevity

In population studies on aging, the data on genetic markers are often collected for individuals from different age groups. The purpose of such studies is to identify, by comparison of the frequencies of selected genotypes, "longevity" or "frailty" genes in the oldest and in younger groups of individuals. To address questions about more-complicated aspects of genetic influence on longevity, additional information must be used. In this article, we show that the use of demographic information, together with data on genetic markers, allows us to calculate hazard rates, relative risks, and survival functions for respective genes or genotypes. New methods of combining genetic and demographic information are discussed. These methods are tested on simulated data and then are applied to the analysis of data on genetic markers for two haplogroups of human mtDNA. The approaches suggested in this article provide a powerful tool for analyzing the influence of candidate genes on longevity and survival. We also show how factors such as changes in the initial frequencies of candidate genes in subsequent cohorts, or secular trends in cohort mortality, may influence the results of an analysis.     

A test of the metabolic theory of ecology with two longevity data sets reveals no common cause of scaling in biological times

相似文献   

Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.

When it was first proposed that the budding yeast Saccharomyces cerevisiae might serve as a model for human aging in 1959, the suggestion was met with considerable skepticism. Although yeast had proved a valuable model for understanding basic cellular processes in humans, it was difficult to accept that such a simple unicellular organism could provide information about human aging, one of the most complex of biological phenomena. While it is true that causes of aging are likely to be multifarious, there is a growing realization that all eukaryotes possess surprisingly conserved longevity pathways that govern the pace of aging. This realization has come, in part, from studies of S. cerevisiae, which has emerged as a highly informative and respected model for the study of life span regulation. Genomic instability has been identified as a major cause of aging, and over a dozen longevity genes have now been identified that suppress it. Here we present the key discoveries in the yeast-aging field, regarding both the replicative and chronological measures of life span in this organism. We discuss the implications of these findings not only for mammalian longevity but also for other key aspects of cell biology, including cell survival, the relationship between chromatin structure and genome stability, and the effect of internal and external environments on cellular defense pathways. We focus on the regulation of replicative life span, since recent findings have shed considerable light on the mechanisms controlling this process. We also present the specific methods used to study aging and longevity regulation in S. cerevisiae.     

An evidence-based approach to identify aging-related genes in Caenorhabditis elegans

Background

Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C. elegans.

Results

We developed a semantic knowledge base for aging by integrating data about C. elegans genes from WormBase with data about 2005 human and model organism genes from GenAge and 149 genes from GenDR, and with the Bio2RDF network of linked data for the life sciences. Using HyQue (a Semantic Web tool for hypothesis-based querying and evaluation) to interrogate this knowledge base, we examined 48,231 C. elegans genes for their role in modulating lifespan and aging. HyQue identified 24 novel but well-supported candidate aging-related genes for further experimental validation.

Conclusions

We use semantic technologies to discover candidate aging genes whose effects on lifespan are not yet well understood. Our customized HyQue system, the aging research knowledge base it operates over, and HyQue evaluations of all C. elegans genes are freely available at http://hyque.semanticscience.org.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0469-4) contains supplementary material, which is available to authorized users.     

The Princeton Protein Orthology Database (P-POD): a comparative genomics analysis tool for biologists

Many biological databases that provide comparative genomics information and tools are now available on the internet. While certainly quite useful, to our knowledge none of the existing databases combine results from multiple comparative genomics methods with manually curated information from the literature. Here we describe the Princeton Protein Orthology Database (P-POD, http://ortholog.princeton.edu), a user-friendly database system that allows users to find and visualize the phylogenetic relationships among predicted orthologs (based on the OrthoMCL method) to a query gene from any of eight eukaryotic organisms, and to see the orthologs in a wider evolutionary context (based on the Jaccard clustering method). In addition to the phylogenetic information, the database contains experimental results manually collected from the literature that can be compared to the computational analyses, as well as links to relevant human disease and gene information via the OMIM, model organism, and sequence databases. Our aim is for the P-POD resource to be extremely useful to typical experimental biologists wanting to learn more about the evolutionary context of their favorite genes. P-POD is based on the commonly used Generic Model Organism Database (GMOD) schema and can be downloaded in its entirety for installation on one's own system. Thus, bioinformaticians and software developers may also find P-POD useful because they can use the P-POD database infrastructure when developing their own comparative genomics resources and database tools.     

TGB: the tobacco genetics and breeding database

The germplasm of the genus Nicotiana contains more than 5,000 accessions and plays an important role in modern biological research. Tobacco can be used as a model system to develop methodologies for plant transformation and for investigating gene function. In order to develop the study of Nicotiana, a large quantity of data on germplasm, sequences, molecular markers and genetically modified tobacco was required for in-depth and systematic collation and research. It became necessary to establish a special database for tobacco genetics and breeding. The tobacco genetics and breeding (TGB, http://yancao.sdau.edu.cn/tgb) database was developed with the aim of bringing together tobacco genetics and breeding. The database has three main features: (1) a materials database with information on 1,472 Nicotiana germplasm accessions, as well as updated genomic and expressed sequence tag (EST) data available from the public database; (2) a molecular markers database containing a total of 12,388 potential intron polymorphisms 10,551 EST-simple sequence repeat (EST-SSR) and 66,297 genomic-SSR markers; and (3) an applications database with genetic maps and some genetically modified studies in tobacco. The TGB database also makes Basic Local Alignment Search Tool and primer designing tools publicly available. As far as can be ascertained, the TGB database is the first tobacco genetics and breeding database to be created, and all this comprehensive information will aid basic research into Nicotiana and other related plants. It will serve as an excellent resource for the online tobacco research community.     

Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research

A recent paper by Deelen et al. (2014) in Human Molecular Genetics reports the largest genome-wide association study of human longevity to date. While impressive, there is a remarkable lack of association of genes known to considerably extend lifespan in rodents with human longevity, both in this latest study and in genetic association studies in general. Here, I discuss several possible explanations, such as intrinsic limitations in longevity association studies and the complex genetic architecture of longevity. Yet one hypothesis is that the lack of correlation between longevity-associated genes in model organisms and genes associated with human longevity is, at least partly, due to intrinsic limitations and biases in animal studies. In particular, most studies in model organisms are conducted in strains of limited genetic diversity which are then not applicable to human populations. This has important implications and, together with other recent results demonstrating strain-specific longevity effects in rodents due to caloric restriction, it questions our capacity to translate the exciting findings from the genetics of aging to human therapies.     

Methods for structuring scientific knowledge from many areas related to aging research

Aging and age-related disease represents a substantial quantity of current natural, social and behavioral science research efforts. Presently, no centralized system exists for tracking aging research projects across numerous research disciplines. The multidisciplinary nature of this research complicates the understanding of underlying project categories, the establishment of project relations, and the development of a unified project classification scheme. We have developed a highly visual database, the International Aging Research Portfolio (IARP), available at AgingPortfolio.org to address this issue. The database integrates information on research grants, peer-reviewed publications, and issued patent applications from multiple sources. Additionally, the database uses flexible project classification mechanisms and tools for analyzing project associations and trends. This system enables scientists to search the centralized project database, to classify and categorize aging projects, and to analyze the funding aspects across multiple research disciplines. The IARP is designed to provide improved allocation and prioritization of scarce research funding, to reduce project overlap and improve scientific collaboration thereby accelerating scientific and medical progress in a rapidly growing area of research. Grant applications often precede publications and some grants do not result in publications, thus, this system provides utility to investigate an earlier and broader view on research activity in many research disciplines. This project is a first attempt to provide a centralized database system for research grants and to categorize aging research projects into multiple subcategories utilizing both advanced machine algorithms and a hierarchical environment for scientific collaboration.     

A pharmacological network for lifespan extension in Caenorhabditis elegans

One goal of aging research is to find drugs that delay the onset of age‐associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans.     

利用TIGR番茄基因索引分析挖掘果实成熟相关基因

目前,互联网上提供许多关于基因及其相关信息的数据库,从这些资料库中提取的资料信息,可用于遗传,生化,分子生物学等各种形式的研究。TIGR Tomato Gene Index数据库中的信息为研究番茄果实成熟开辟了新思路。本研究通过对该数据库的分析,发现了一些在番茄果实成熟过程中差异表达的基因。并进一步通过基因芯片软件和文献挖掘的方法对这些基因进行了分析,结果发现了一些新的与果实成熟相关的基因。这对研究番茄果实成熟提供有价值的信息和思路。