Dataset Information

Mouse multi-organ age-associated protein changes across life stages

ABSTRACT: Ageing is a key risk factor for disease and mortality in humans and other animals, with most insights derived from genomic, epigenomic, and transcriptomic studies. However, large-scale datasets on age-related changes at the protein level remain scarce. To fill this gap, we performed a comprehensive quantitative proteomic analysis across eight major organs—brain, heart, lungs, liver, kidneys, spleen, skeletal muscle, and testis—in male C57BL/6J mice, sampled at key life stages: young adult (3–5 months), adult (8 months), mid-life (14 months), and late life (20–26 months). Our results revealed diverse rates of protein expression changes, ranging from rapid (kidneys, spleen) to moderate (liver, lungs) to minimal (skeletal muscle, testis) and subtle (heart, brain). Aging onset appeared earlier in the spleen and kidneys compared to the liver and lungs. By isolating the non-blood proteome, we identified enriched organ-specific processes like oxidative phosphorylation (kidneys) and lipid metabolism (liver), along with shared processes across organs. These findings provide valuable insights into organ-specific and shared protein dynamics underlying age-related diseases.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Dr. Dan Ehninger

PROVIDER: PXD058684 | JPOST Repository | Tue Jun 17 00:00:00 GMT+01:00 2025

REPOSITORIES: jPOST

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			Action	DRS
	Mar032021_Br_25_20M_c3055_120min_60K_7-15K_TopS.raw	Raw
	Mar032021_Br_26_26M_c2293_120min_60K_7-15K_TopS.raw	Raw
	Mar032021_Br_27_3M_c1114_120min_60K_7-15K_TopS.raw	Raw
	Mar032021_Br_28_5M_c3671_120min_60K_7-15K_TopS.raw	Raw
	Mar032021_Br_29_8M_c1378_120min_60K_7-15K_TopS.raw	Raw

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Publications

Proteomic aging signatures across mouse organs and life stages.

Scifo Enzo E Morsy Sarah S Liu Ting T Xie Kan K Schaaf Kristina K Bano Daniele D Ehninger Dan D

The EMBO journal 20250715 16

Aging is associated with the accumulation of molecular damage, functional decline, increasing disease prevalence, and ultimately mortality. Although our system-wide understanding of aging has significantly progressed at the genomic and transcriptomic levels, the availability of large-scale proteomic datasets remains limited. To address this gap, we have conducted an unbiased quantitative proteomic analysis in male C57BL/6J mice, examining eight key organs (brain, heart, lung, liver, kidney, sple ...[more]

PMID: 40664891

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Project description:BackgroundAging 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.MethodsTo 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. ResultsProteomic 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 3,779 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.ConclusionsThis 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.