Measuring biological age in mice using differential mass spectrometry

Harris Bell-Temin, Matthew J. Yousefzadeh, Andrey Bondarenko, Ellen Quarles, Jacqueline Jones-Laughner, Paul D. Robbins, Warren Ladiges, Laura J. Niedernhofer, Nathan A. Yates

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aging is an ill-defined process that increases the risk of morbidity and mortality. Aging is also heterogeneous meaning that biological and chronological age can differ. Here, we used unbiased differential mass spectrometry to quantify thousands of proteins in mouse liver and select those that that consistently change in expression as mice age. A panel of 14 proteins from inbred C57BL/6 mice was used to equate chronological and biological age in this reference population, against which other mice could be compared. This "biological age calculator" identified two strains of f1 hybrid mice as biologically younger than inbred mice and progeroid mice as being biologically older. In an independent validation experiment, the calculator identified mice treated with rapamycin, known to extend lifespan of mice, as 18% younger than mice fed a placebo diet. This demonstrates that it is possible to measure subtle changes in biologic age in mammals using a proteomics approach.

Original languageEnglish (US)
Pages (from-to)1045-1061
Number of pages17
JournalAging
Volume11
Issue number3
DOIs
StatePublished - Feb 11 2019

Bibliographical note

Funding Information:
We gratefully acknowledge the contributions of the Geropathology Grading Committee for validating the composite lesion scores on mouse liver. We are also grateful to Sara McGowan and the Scripps Florida Animal Resource Center for help with animal husbandry and tissue collection. This work was supported by the National Institutes of Health grant P01 AG043376. This project used the Hillman Cancer Proteomics Facility / Biomedical Mass Spectrometry Center that is supported in part by award P30CA047904. WL was supported by NIA R24 AG047115.

Keywords

  • Aging
  • Liver
  • Mass spectrometry
  • Mouse
  • Non-targeted
  • Proteomics
  • Surrogate markers

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