AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging

Abstract

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.

Graphical Abstract

Figure 1.

Database content and construction of AgeAnnoMO. Public resources and the aging-related multi-omics datasets were collected for the aging-related functional annotations. For each data modality, we performed functional annotations to characterize the aging hallmarks. Users can browse the functional annotations by each aging hallmark. Users can also browse the datasets by species. AgeAnnoMO also supports searching and downloading information on aging-related genes, mitochondrial genes, proteins, TCR/BCR sequences, metabolites and microbiotas.

Figure 2.

Examples from functional annotations of primary aging hallmarks. (A) Identification of mutation shows PSEN2 may have mutations across species. (B) eQTL analysis shows that mutation on Psen2 in mouse may potentially regulate the expression of Stfa2l1. (C) Mbnl2 shows hypermethylation in the aged mouse. (D) MBNL2 shows hypermethylation in elderly individuals. The red line on the chromosome shows the location of the DMR. (E) The abundance of MTOR protein shows upregulation during aging across different species. (F) The interaction of MTOR protein according to the protein interaction network. (G) The proportion of antigen specificity in the young group in the mouse liver. (H) The proportion of antigen specificity in the aged group in the mouse liver.

Figure 3.

Examples from functional annotations of antagonistic and integrative aging hallmarks. (A) Nicotinamide shows differential abundance between age groups across human and mouse tissues. (B) Circular network plot of the mouse skin of the young group. (C) Circular network plot of the mouse skin of the aged group. Nodes with colors represent different cell types, while the edges represent ligand-receptor interactions between two cell types. (D) Cell map by cell clusters of mouse skin. (E) Cell map by age group of mouse skin. (F) The potential interactions between Firmicutes phylum and the associated genes according to published database.

Figure 4.

The main functions and usages of AgeAnnoMO. (A) The top navigation bar shows the main functions of AgeAnnoMO. (B) Users can browse the results of functional analyses related to each aging hallmark. (C) Users can also access the datasets and corresponded results based on species. (D) The ‘Search’ function allows users to choose the data modality, species and input the genes, proteins, TCR/BCR sequences, metabolites or microbiotas of interests. (E) Data download function in AgeAnnoMO. Users can access all annotation results in GitHub project. (F) ‘Help’ function contains a brief description of AgeAnnoMO and its main functions. (G) ‘Datasets’ function contains the detailed information of all datasets included in AgeAnnoMO.