Geroprotectors: the most complete database (3)

Alexey Moskalev et al., AGING, 2015: 

Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease 

translated by Evgenia Ryabtseva

(The end, the beginning of the article is here.)

The Geroprotectors database integrates information presented in the form of four blocks (Fig. 2):

1. Experiments on the study of life expectancy: summaries and abstracts (abstracts) of research results demonstrating the effects of a certain compound that increase life expectancy.
2. Compounds: Information about geroprotective compounds.
3. Mechanisms: involvement of the compound in the well-known mechanisms of longevity and slowing down aging.
4. Age-related pathologies: the effect of the compound on prevailing and well-studied age-related conditions and associated diseases.

The connection information is divided into 3 blocks. The first block contains an image, a title and a short description, as well as links to other chemical databases. It also includes information about the number of clinical trials conducted and the status of the drug. The second block contains biological, pharmacological and toxicological information, and also describes the mechanisms of longevity. The third block is devoted to the relationship of each of the compounds with age-related pathologies (chronic inflammation, cancer, accumulation of beta-amyloid, etc.).

Figure 2. Data structure Geroprotectors.org , demonstrating the division of data into 4 main blocks: experiments, compounds, mechanisms and age-related pathologies, each of which contains numerous blocks of information forming a complete profile for each of the studied geroprotective compounds.

Integration with biochemical databases and databases of medicinal compounds

The description of compounds and mechanisms is compiled using a variety of chemical and biological databases. Compound profiles include a short description, all variants of names, chemical structure, toxicity profile, data on clinical use, biological and pharmacological activity, chemical interactions, etc. All compounds are integrated with key chemical databases, including PubChem, ChemSpider, DrugBank, CHEBIL, UniProt and GenAge. 

List of chemical databases referenced in the database compound profiles Geroprotectors.org (the number of connections represented in each database is indicated in parentheses).

1. PubChem https://pubchem.ncbi.nlm.nih.gov/ (209) [28, 29]
2. ChemSpider http://www.chemspider.com/ (208) [36-38]
3. ChEMBL https://www.ebi.ac.uk/chembl/ (193) [33-35]
4. ChEBI https://www.ebi.ac.uk/chebi/ (158) [30-32]
5. Drug Bank http://www.drugbank.ca/ (98) [39-42]

Comparison with existing databases

Currently, there are already several databases with free access dedicated to research in the field of aging, each of which is created to meet a specific need and is based on a unique approach (see the table). Some of these databases do contain information about geroprotectors, especially the AgeFactDB database created by the JenAge Center, which contains profiles of 91 compounds associated with aging, as well as genes and other aging-related interventions. However, none of them provides a complete list of confirmed and potential geroprotectors and a complete information summary for each of the compounds. Also, none of them contains biochemical and mechanistic profiles of geroprotective compounds integrated with external databases. At the time of its launch Geroprotectors.org describes more than twice as many geroprotectors as any of the other databases devoted to aging. Moreover, it provides much more information on each of the connections individually and is regularly checked manually, which ensures that the information is always up to date.

A list of existing databases dedicated to aging, for comparison with Geroprotectors.org

A researcher working with Caenorhabditis elegans roundworms wants to study the known geroprotective effects of resveratrol and visits Geroprotectors.org to get information that will help him in planning the experiment. On the home page, it searches for the word Resveratrol. The search results contain seven links to experiments conducted on four model organisms that demonstrated the geroprotective effects of resveratrol [60-66]. These links are presented in the format of a simple table, the number of rows in which corresponds to the number of studies mentioned. The columns contain the average value, median and maximum increase in life expectancy as a percentage for each of the studies, as well as reference links to PubMed. 

Using, for example, the median life expectancy, the researcher can instantly see that there are data indicating the ability of resveratrol to increase this indicator by 10-10.7% for C.elegans [62,63,66], by 56% – for fish Nothobranchius furzeri (Nothobranchius furzeri) and by 13% – for fruit flies-Drosophila melanogaster) [64]. At this stage , the scientist can choose one of two options for further actions:

• go directly to the literature, in which you can read more about any of the listed seven studies, by clicking on the corresponding PubMed links in the last column of the table or
• learn more about the properties of resveratrol and the research data in the framework of geroprotectors.org . 

Interested in a quick extensive analysis of the properties of resveratrol and more detailed information about the increase in the lifespan of C.elegans, the user chooses the latter option and remains in the Geroprotectors database. Clicking on the link "Resveratrol" in any row of the table gives a page with a summary of resveratrol. It includes a schematic image of the chemical structure of resveratrol, and the labels located above this image allow you to choose one of three options for a summary of the drug: information about the compound, bioactivity/ pharmacology/mechanisms or experiments on pancreas (life expectancy), English Compound Info, Bioactivity/Pharm/ Pathways, or LS Experiments.

Since the section "information about the compound" corresponds to the active label (with an image of the structure of resveratrol), the researcher starts with it. When scrolling down the page, the official name and other variants of the name of the compound appear, a link to the article of the drug in Wikipedia, as well as links to chemical databases and databases of medicines Chemspider, DrugBank, ChEMBL, ChEBI, PubChem). At the very bottom of the page, the current status of resveratrol (experimental, investigational) is indicated, as well as the number of ongoing clinical trials of the drug (in this case – 95). To get immediate access to them, the researcher can use the link to clinicaltrials.org . 

The second label "Bioactivity/Pharmacology/Mechanisms" helps the researcher to deepen knowledge about the biological activity of resveratrol. On the left is a list of more than 30 interactions that resveratrol enters into, taken from the UniProt database and provided with appropriate links. On the right, the researcher can see that resveratrol is able to have several types of effects on the body, including anti-inflammatory, anti-cancer, anti-atherogenic, anti-obesity, neuroprotective and cardioprotective. Here are links to studies whose results confirm each of the listed effects. 

Below the list of effects on the body is a short summary of the antibacterial, antifungal and antiviral effects of the drug, presented in the yes/no format. From it, the researcher learns about the absence of resveratrol of all these properties. 

Scrolling down the page opens a list of the mechanisms of action of resveratrol that ensure longevity. It includes reproducing the effects of a low-calorie diet and resistance to stress, as well as mechanisms for suppressing aging processes, which in the case of resveratrol include antioxidant properties. Finally, the statement at the bottom of the page indicates whether there is a relationship between resveratrol and biomarkers of aging (does not exist). And in the lower left corner of the page, the researcher can find the associated mechanisms and LD50 levels indicating the degree of toxicity.

If the researcher still wants to learn more about experiments to increase life expectancy with resveratrol, he can use the label "experiments on pancreas" for this. When you go to the corresponding page on the left, the title and abstract of one of the seven articles listed in the table that appears after the search results home page opens. This abstract refers to an experiment with baker's yeast (Saccharomyces cerevisiae) [61]. This and the other six articles can be accessed using the shortcuts at the top of the page. 

To proceed to experiments on C.elegans, the researcher clicks on one of the two labels for C.elegans, after which the name and abstract of one of the three studies appear. Under the abstract, the researcher can see that the N2 line of worms was used in it. The conditions of the experiment are listed on the right, namely, the medium for growing nematodes based on agar with the addition of E.coli (E.coli) of the OP5 line, as well as the fact that the median increase in life expectancy in this study was 17.8% [62]. It is also indicated here that the maximum effect of resveratrol in this study was obtained at a drug concentration of 1 millimol. Further scrolling down opens an additional link to the study, during which the opposite effect was obtained.

Availability

The Geroprotectors database is available at http://www.geroprotectors.org , and the data contained therein is subject to a Creative Commons license that permits their use in other analyses. Using the export tool, you can download either the entire database or a narrower set of information. Feedback via e-mail is welcome, as well as the entry of new data, for which there is a special form that provides the introduction of all necessary information.

Discussion

Geroprotectors.org It is a unique database with free online access. Other databases devoted to aging, as a rule, provide basic information about longevity/mortality genes, genomes of long-lived species (naked digger, bowhead whale, etc.), as well as theories of aging and contain relatively little data on anti-aging interventions. Geroprotectors.org Provides information on the life-extending effects of more than 200 herboprotective compounds, as well as summaries of other key data on these compounds through a fast-running, intuitive and transparent interface. The data contained in it are obtained from more than 250 peer-reviewed studies, as well as chemical databases and drug databases. All data are presented in the form of summaries and are cross-referenced everywhere, providing quick and convenient access to original publications. 

In addition to efforts aimed at ensuring accuracy, additional efforts have been made to include studies in the database whose results refute the geroprotective effects of compounds. This is done to ensure the objectivity and versatile presentation of each connection. Since aging will continue to approach the top of the list of social and economic problems over the coming decades, the need for resources like Geroprotectors, providing a multidisciplinary community of biogerontologists and clinicians with the opportunity to join forces and share their knowledge, will only increase. As a response to this need, Geroprotectors provides researchers interested in finding methods to combat aging with a valuable source of information.

The list of references to the article is given on a separate page.

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30.09.2015