Evidence map›Paper›PMID 40404760›Full record

ArticleNature communications2025

Expanding the landscape of aging via orbitrap astral mass spectrometry and tandem mass tag integration.

Gregory R Keele, Yue Dou, Seth P Kodikara, Erin D Jeffery, Dina L Bai, Erik Hultenius, Zichen Gao, Joao A Paulo, Steven P Gygi, Xiao Tian and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Gregory R Keele *GenOmics, Bioinformatics, and Translational Research Center, RTI International, Research Triangle Park, NC, USA.ORCID http://orcid.org/0000-0002-1843-7900
Yue Dou *Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Seth P KodikaraDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Erin D JefferyDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0001-9511-7719
Dina L BaiDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Erik HulteniusSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Zichen GaoSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4291-413X
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7626-0034
Xiao TianSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Tian ZhangDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, USA. cgm8ck@virginia.edu.ORCID http://orcid.org/0000-0001-9007-7965

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Developing proteomics pipelines to improve depth, throughput, and accuracyR35GM156406 · NIGMS · HARVARD MEDICAL SCHOOL · PI Joao A Paulo · 2025 to 2026
$878k
A new multi-pathway kinase activity assay applied to compound library screening in cancer biologyR00CA273170 · NCI · UNIVERSITY OF VIRGINIA · PI ZHANG, TIAN · 2023 to 2025
$747k
Epigenetic Reprogramming to Counteract Neuronal Aging and DegenerationR00AG068303 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI XIAO TIAN · 2024 to 2026
$742k
NCI NIH HHS P30 CA030199NCI NIH HHS R00 CA273170NIA NIH HHS R00 AG068303NIGMS NIH HHS R35 GM156406U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30CA030199U.S. Department of Health & Human Services | National Institutes of Health (NIH) R00AG068303U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM156406U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5R00CA273170
6 · The paper itself

Abstract

Aging results in a progressive decline in physiological function due to the deterioration of essential biological processes. While proteomics offers insights into aging mechanisms, prior studies are limited in proteome coverage and lifespan range. To address this, we integrate the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of cortex, hippocampus, striatum and kidney in the C57BL/6JN mice, quantifying 8,954 to 9,376 proteins per tissue (12,749 total). Samples spanned both sexes and three age groups (3, 12, and 20 months), representing early to late adulthood. To improve TMT quantitation accuracy, we develop a peptide-spectrum match-based filtering strategy that leverages resolution and signal-to-noise thresholds. Our analysis uncovers distinct tissue-specific patterns of protein abundance, with age and sex differences in the kidney and primarily age-related changes in brain tissues. We also identify both linear and non-linear proteomic trajectories with age, revealing complex protein dynamics over the adult lifespan. Integrating our findings with early developmental proteomic data from brain tissues highlights further divergent age-related trajectories, particularly in synaptic proteins. This study provides a robust data analysis workflow for Orbitrap Astral-based TMT analysis and expands the proteomic understanding of aging across tissues, ages, and sexes.

Indexed as

AgingMass SpectrometryProteomeProteomicsTandem Mass SpectrometryAnimalsBrainFemaleHippocampusKidneyMaleMiceMice, Inbred C57BLProteome

Identifiers

PMID40404760
PMCPMC12098839

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.