Proteomics

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Expanding the Landscape of Aging via Orbitrap Astral Mass Spectrometry and Tandem Mass Tag (TMT) Integration


ABSTRACT: Aging results in progressive decline in physiological function due to the deterioration of essential biological processes, such as transcription and RNA splicing, ultimately increasing mortality risk. Although proteomics is emerging as a crucial tool for elucidating the molecular underpinnings of aging, existing studies are constrained by limited proteome coverage and only observe a narrow range of lifespan. To overcome these limitations, we employed the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of three brain tissues (cortex, hippocampus, striatum) and kidney in the C57BL/6 mouse model, achieving high-resolution quantification, ranging from 8,954 to 9,376 proteins per tissue. Our sample population represents balanced sampling across both sexes and three age groups (3, 12, and 20 months), comprising approximately young adulthood to early late life (~20-60 years-old for human lifespan). To enhance quantitative accuracy, we developed a rigorous peptide filtering strategy based on resolution and signal-to-noise thresholds. Our analysis uncovered distinct tissue-specific patterns of protein abundance, with pronounced age and sex differences in the kidney, contrasted by limited sex differences in brain tissues. Notably, we identified both continuous and non-continuous age-associated proteomic changes, revealing complex protein dynamics over adult lifespan. Integrating our findings with early developmental proteomic data from brain tissues highlighted further divergent age-related trajectories, particularly in synaptic proteins. This study not only expands the proteomic landscape of aging, but also underscores the utility of Orbitrap Astral Mass Spectrometry for capturing age-associated molecular alterations with unprecedented depth.

INSTRUMENT(S): Orbitrap Astral

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Kidney

SUBMITTER: Tian Zhang  

LAB HEAD: Tian Zhang

PROVIDER: PXD058160 | Pride | 2025-04-03

REPOSITORIES: Pride

Dataset's files

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Action DRS
622625_az01271_02152024.mzid.gz Mzid
622626_az01270_02152024.mzid.gz Mzid
622627_az01268_02152024.mzid.gz Mzid
622628_az01269_02152024.mzid.gz Mzid
622629_az01263_02152024.mzid.gz Mzid
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