Research Paper Volume 11, Issue 3 pp 1045—1061

Measuring biological age in mice using differential mass spectrometry

Harris Bell-Temin 1, , Matthew J. Yousefzadeh 2, 3, , Andrey Bondarenko 4, , Ellen Quarles 5, , Jacqueline Jones-Laughner 6, , Paul D. Robbins 2, 3, , Warren Ladiges 7, , Laura J. Niedernhofer 2, 3, , Nathan A. Yates 1, 6, ,

  • 1 Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
  • 2 Department of Molecular Medicine, The Scripps Research Institute, Florida , Jupiter, FL 33458, USA
  • 3 Department of Biochemistry, Molecular Biology and Biophysics, and the Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN 55455, USA
  • 4 Infoclinika, Bellevue, WA 98006, USA
  • 5 Department of Pathology, University of Washington, Seattle, WA 98195, USA
  • 6 Biomedical Mass Spectrometry Center, University of Pittsburgh Schools of the Health Sciences, Pittsburgh, PA 15261, USA
  • 7 Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA

received: January 14, 2019 ; accepted: January 29, 2019 ; published: February 11, 2019 ;

https://doi.org/10.18632/aging.101810
How to Cite

Copyright: Bell-Temin et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

CA3: carbonic anhydrase 3 protein; CLS: composite lesion score; dMS: differential mass spectrometry; GGP: Geropathology Grading Platform; MS: mass spectrometry; nLC-MS: nanoflow liquid chromatography high-resolution mass spectrometry; m/z: mass-to-charge ratio (of a mass-spectrometry feature); rt: retention time (of a mass-spectrometry feature); i: intensity (of a mass-spectrometry feature); WT: wild-type.