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PreprintCC BYbioRxiv

Comparative proteomic quantification reveals novel longevity regulators

1 more authors
  1. 1Janelia Research Campus, Howard Hughes Medical Institute

Abstract

Proteomics is a powerful tool for profiling the protein landscape underlying cellular and physiological processes. Advances in mass spectrometry-based methods, such as tandem-mass-tags (TMT) isobaric labeling-based proteomics at both MS2 and MS3, label-free quantification (LFQ) with data-dependent-acquisition (DDA) or data-independent acquisition (DIA)-based proteomics, and stable isotope labeling with amino acid (SILAC) spike-in-assisted proteomics, enable quantitative proteome comparisons across biological conditions. These five quantitative proteomic methods offer distinct advantages in coverage, throughput, and quantitative reproducibility. Here, we treated them as orthogonal approaches, retaining protein candidates with significant, consistent-direction changes supported across multiple independently instrumented methods to identify high-confidence protein-level changes associated with longevity. Insulin/insulin-like growth factor signaling (IIS) is a highly conserved longevity regulatory pathway from Caenorhabditis elegans to humans. By quantitatively profiling IIS mutants in C. elegans and performing genetic screening, we obtained a systems-view of proteomic changes linked to longevity and identified new longevity regulators. This systematic cross-method comparison also serves as a valuable resource for guiding the selection of quantitative proteomics approaches.

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BibTeX
@misc{ding2026comparative,
  title = {{Comparative proteomic quantification reveals novel longevity regulators}},
  author = {L. Ding and H. Lin and C. Huang and V. Vallanadu and K. Ashley and S. R. Pitts and A. S. Mutlu and Y. Zhou and X. Ma and J. M. Choi and F. Jin and J. Wang and M. C. Wang},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.06.757189},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757189v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Comparative proteomic quantification reveals novel longevity regulators
AU  - L. Ding
AU  - H. Lin
AU  - C. Huang
AU  - V. Vallanadu
AU  - K. Ashley
AU  - S. R. Pitts
AU  - A. S. Mutlu
AU  - Y. Zhou
AU  - X. Ma
AU  - J. M. Choi
AU  - F. Jin
AU  - J. Wang
AU  - M. C. Wang
PY  - 2026
DA  - 2026/10/06
PB  - bioRxiv
DO  - 10.64898/2026.10.06.757189
UR  - https://www.biorxiv.org/content/10.64898/2026.10.06.757189v1
AB  - Proteomics is a powerful tool for profiling the protein landscape underlying cellular and physiological processes. Advances in mass spectrometry-based methods, such as tandem-mass-tags (TMT) isobaric labeling-based proteomics at both MS2 and MS3, label-free quantification (LFQ) with data-dependent-acquisition (DDA) or data-independent acquisition (DIA)-based proteomics, and stable isotope labeling with amino acid (SILAC) spike-in-assisted proteomics, enable quantitative proteome comparisons across biological conditions. These five quantitative proteomic methods offer distinct advantages in coverage, throughput, and quantitative reproducibility. Here, we treated them as orthogonal approaches, retaining protein candidates with significant, consistent-direction changes supported across multiple independently instrumented methods to identify high-confidence protein-level changes associated with longevity. Insulin/insulin-like growth factor signaling (IIS) is a highly conserved longevity regulatory pathway from Caenorhabditis elegans to humans. By quantitatively profiling IIS mutants in C. elegans and performing genetic screening, we obtained a systems-view of proteomic changes linked to longevity and identified new longevity regulators. This systematic cross-method comparison also serves as a valuable resource for guiding the selection of quantitative proteomics approaches.
ER  -