Aging diagram
A public resource for quick search analysis of mechanisms,
involved in the aging process
Alexey Moskalev et al., Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes // Nucleic Acids Research, 2016.
Abbreviated translation: Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru
Simultaneously with the rapid aging of the world population, there is an increase in the incidence of age-related diseases, as well as the need for expensive long-term medical care (1-4). In the context of reducing the burden caused by this shift, scientific knowledge and innovation will become increasingly critical, and disease prevention strategies will acquire the status of national and international priorities. The study of aging as a field of science will develop rapidly. However, despite everything, it faces a number of difficulties and its development needs to be guided.
One of the difficulties is the lack of a publicly available detailed database of biological mechanisms associated with aging and an encyclopedia of data on aging. Biological pathways are one of the most powerful tools for understanding biological processes (5). They provide an intuitive system view of the interactions between the many individual elements of each process individually. In addition, they can be interactive for user-controlled search and compatible with calculation methods, they are also necessary for studying large datasets in which a lot of individual changes may reflect a small number of more biologically important (and with greater statistical power) changes at the organism level (6). Databases of biological pathways are a key component of many publicly available biological data repositories (7).
The aging process is particularly well suited for presentation in the form of a database of biological pathways. Complex sequences of strictly organized events and a variety of internal and external factors interacting during the aging process can be optimally captured in the form of a complex of descending biological mechanisms at the system level, illustrating and characterizing the nature of these interactions.
The compilation of characteristics of aging mechanisms can not only help in the creation of theories of aging, but also actually form the basis of breakthroughs in the development of anti-aging interventions. Examples of practical applications include: (i) targeted work with aging-associated signaling pathways during screening of anti-aging compounds or geroprotectors (8), (ii) imitation of mechanisms underlying anti-aging interventions with limited practical application (for example, a low-calorie diet) using pharmacological or other methods, and (iii) comparison mechanisms modified in age-related diseases, with those characteristic of normally aging cells (9-12) to identify aging processes that can simultaneously be mechanisms of disease development.
The lack of a database of aging mechanisms to date may be a reflection of the immaturity of this field of research, but it is also partly due to the huge variety of processes associated with aging. Their detailed description is a monumental task. Aging itself is a complex process that occurs at all levels of all systems of our body, leading to loss of functions and triggering the development of a number of diseases. There is currently a debate about whether aging as such is a curable disease (13). The field of aging research itself includes a very diverse community of scientists with different perspectives.
In order to create a unified scheme of aging mechanisms, the community needs a platform that allows us to jointly, stage by stage, compile mechanisms from the available data that will eventually allow us to formulate a unified theory.
Previously, numerous attempts have been made to structure data and knowledge about aging on the Internet (14-19), but there is still a need for a fast, intuitive visual representation of aging processes, including all components, from environmental trigger stimuli to molecular interactions.
As far as the authors know, there is no such resource today. In order to fill this niche, they developed the Aging Chart (Aging Diagram) is a database of biological mechanisms edited and peer–reviewed by a community of experts and an encyclopedia of aging processes created on the basis of a wiki engine.
Aging Chart will be an addition and part of the existing complex of publicly available databases and knowledge about aging.
Community Review Model
Mechanism databases are only useful if they are reliable. As new data becomes available, it is necessary to maintain the reliability of existing information.
The content of the mechanisms does not immediately appear in the form of raw data, it must be manually integrated, in most cases from literary sources, while each individual interaction between the elements must be validated using a peer-reviewed publication. In the past, this work was carried out by small groups of experts, however, as the flow of new data exhausted their capabilities, preventing obsolescence and gaps in a centrally reviewed database became a difficult task (7). In the end, it was proposed to involve a community of experts in this task. Collaboration within the community, as well as joint database review, has become a new model designed to solve this problem (7,20,21).
The WikiPathways platform, which appeared in 2008, was the first successful attempt to create a community-reviewed mechanism database model (20). On the model of Wikipedia, it was presented as an editable open access platform based on a wiki engine, designed in such a way as to make it as easy as possible to work with it and reduce barriers for users who are poorly versed in the technical side of the issue who want to contribute to its content. It was a great success (20) and gained an active audience of readers and participants. The quality of its content corresponds to the quality of the published data, which confirms the role of cooperation within the community as a factor that enhances quality control, and not vice versa. Wiki-engine-based models have also demonstrated their viability when creating other biological applications, such as the Gene Wiki portal, (22) part of Wikipedia, and the community-annotated resource Wikiproteins (23).
The range of information contained in the WikiPathways is very wide, it includes all areas of biology and all organisms of interest, while it also includes several portals linking it to earlier databases and other, more specific databases of mechanisms related to the most interesting subsections – for example, reagent (24) and micronutrients (25). The development and continued success of these databases demonstrates the need for the emergence of domain-specific mechanisms and other information databases, and also indicates that a community-edited database of aging mechanisms will similarly flourish, for which there are a number of reasons. Firstly, the smaller audience will be balanced by the higher competence of the participants. Secondly, less complex and more specific mechanisms may be more preferable than intertwining tangled mechanisms of a higher level. Thirdly, specific databases provide a squeeze of information for scientists engaged in related areas of research and having a limited amount of time, thus contributing to the development of relatively new or highly multidisciplinary fields, such as aging. Finally, issue-specific databases of mechanisms can help to increase the community and cooperation within it.
Currently, neither on WikiPathways nor on other platforms there is a specialized portal that would provide access to the mutually intertwining mechanisms involved in the processes of aging and longevity. Aging Chart is the first attempt to create such a database.
Aging Chart: A community-reviewed database of mechanisms of the aging process
The authors created the Aging Chart in response to the growing need for a database of aging mechanisms to combine, integrate and provide a visual diagram of the large amount of information available today about the aging process.
In accordance with the parameters of the model of cooperation within the community, Aging Chart is a complex editable system designed to contain and redirect the horizontal growth of the field of aging studies by focusing data on the aging process on one mechanism-oriented, community-reviewed site, whose users can easily both extract and add content and integrate it into the visual intuitively a clear general scheme.
Compiled from carefully selected data in the peer-reviewed literature, the Aging Chart debuts presenting 11 mechanisms, networks and conceptual maps relevant to all issues associated with aging, ranging from gene-oriented mechanisms to mechanisms describing aging processes, age-related diseases, longevity factors and anti-aging strategies. All of this is searchable and up-to-date for users who want to contribute. The mechanism diagrams are interactive and have clickable nodes for user-controlled search, providing access to the corresponding pages and mechanisms for each individual element under consideration.
Short text descriptions of modern anti-aging intervention strategies are also available, with active links to peer-reviewed articles in the PubMed database. Aging Chart was created for the same convenience of users with and without technical skills. It provides a platform for the rapid study of almost any aspect of aging that currently has a scientific explanation, as well as for the integration of elements and concepts that can lead to the emergence of new hypotheses and research directions.
The purpose of the Aging Chart launch is the appearance in the public domain of a visual encyclopedia of aging processes, which will be equally useful for both beginners and experts in this field.
The prospects
The MediaWiki engine provides many features that can be used in the future. The next stage of the Aging Chart project will include the development of an advanced search system that will help users find the necessary information in a few mouse clicks. This system will work with external data sources such as PubMed, KEGG, Wikipedia, etc. In addition, it will have its own database, which users will be able to fill in manually. As mentioned above, pop-ups will contain additional information that will be generated automatically by searching in various sources. Another part of the second stage will be the creation of a unified online editor.
After the launch of the Aging Chart, the participation of the audience and the community will be of primary importance. While at the beginning of its work the site contains information about more than 100 mechanisms, the formation of an active group of participants will be a critical task for the continuous construction and updating of new and existing mechanisms on the Aging Chart and cooperation within the community depends on the diligence of its members in ensuring the addition of new data and correction of errors and outdated information. The multifaceted nature of the field of aging research requires that experts from a wide range of research areas be represented in the audience of experts participating in the Aging Chart.
For information of interest only to specialists and references to literary sources, see the full text of the article.
23.03.2016