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Real Time Analysis of Metabolic Profile in Ex Vivo Mouse Intestinal Crypt Organoid Cultures
Published on: November 3, 2014
Ten mouse organs proteome and metabolome atlas from adult to aging
Qingwen Wang1,2, Zhixiao Xu1,2, Xinwen Ding1,2
1Department of Anesthesiology and Surgical Intensive Care Unit, School of Medicine and School of Biomedical Engineering, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, China.
Background:
Aging is a complex biological process characterized by progressive molecular alterations across multiple organ systems, significantly influencing disease susceptibility and mortality. Unraveling molecular interactions driving aging is crucial for interventions promoting healthy aging and mitigating senescence. However, the systemic mechanisms governing both inter-organ interactions and organ-specific aging trajectories remain incompletely characterized.
Methods:
To investigate the molecular dynamics of aging, we conducted a systematic multi-omics analysis of 400 tissue samples collected from 10 organs (brain, heart, intestine, kidney, liver, lung, muscle, skin, spleen, and stomach) in mice at four distinct life stages: 4, 8, 12, and 20 months (from youth to elderly). Proteomic profiling was performed using data-independent acquisition (DIA) technology, while metabolomic analysis was performed in both positive and negative ion modes. Differential expression analysis of proteins and metabolites was employed to construct a comprehensive multi-organ aging dataset.
Results:
Proteomic profiling across ten organs at four age stages identified a total of 14,763 protein groups (PGs). Of these, 18 proteins, including Ighm, C4b, and Hpx, exhibited consistent age-related differential expression patterns across all ten organs. Functional enrichment analysis highlighted the humoral immune response as a primary driver of age-related expression changes. Additionally, this study mapped a set of age-unique proteins, such as Hp, Egf, and Arg, with distinct expression patterns in aging organs. Metabolic analysis identified 3779 metabolites, with key aging-related metabolites such as NAD+, inosine, xanthine, and hypoxanthine showing significant expression changes across multiple organs. Pathway enrichment analysis revealed consistent alterations in purine metabolism, pyrimidine metabolism, riboflavin metabolism, and nicotinate/nicotinamide metabolism during multi-organ aging.
Conclusions:
This study provides a multi-omics atlas of multi-organ aging, revealing both intra- and inter-organ similarities and heterogeneities. These findings offer valuable insights into the molecular mechanisms underlying geriatric health decline and serve as a foundational resource for organism-systematic early warning and targeted interventions against aging-associated pathologies.
Insights
This study reveals consistent molecular changes across multiple organs during aging in mice, highlighting immune responses and metabolic pathways. These findings offer insights into aging mechanisms and potential interventions for age-related diseases.
Area of Science:
- Gerontology and Molecular Biology
- Multi-omics and Systems Biology
Background:
- Aging is a complex biological process with progressive molecular alterations impacting disease susceptibility.
- Understanding systemic mechanisms of aging across organs is crucial for healthy aging interventions.
- Inter-organ interactions and organ-specific aging trajectories are not fully characterized.
Purpose of the Study:
- To systematically investigate the molecular dynamics of aging across multiple organs using a multi-omics approach.
- To identify consistent and unique age-related molecular changes within and across organs.
- To build a foundational resource for understanding aging and developing interventions.
Main Methods:
- Conducted a multi-omics analysis of 400 tissue samples from 10 mouse organs at four life stages (4, 8, 12, 20 months).
- Utilized proteomic profiling (DIA technology) and metabolomic analysis.
- Employed differential expression analysis to construct a multi-organ aging dataset.
Main Results:
- Identified 14,763 protein groups, with 18 proteins consistently changing across all organs, implicating humoral immune response.
- Mapped age-unique proteins and identified 3779 metabolites with significant age-related changes, including NAD+.
- Revealed consistent alterations in purine, pyrimidine, riboflavin, and nicotinate/nicotinamide metabolism.
Conclusions:
- Generated a multi-omics atlas of multi-organ aging, detailing similarities and differences.
- Provided insights into molecular mechanisms of aging and geriatric health decline.
- Established a resource for organism-systematic early warning and targeted interventions against aging-associated pathologies.
