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.

Highlights

  • Aging is the greatest risk factor for the majority of chronic diseases

  • The development of new treatments for aging will depend greatly on the identification of biomarkers that act as surrogates for measuring lifespan and healthspan, which are costly and lengthy to measure in pre-clinical models, let alone in humans [5]

  • Mass spectrometry assays are based on the chemical measurement of specific amino acid sequences, not biological antibody recognition, allowing proteins to be tested across species with absolute molecular specificity

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Summary

Introduction

Aging is the greatest risk factor for the majority of chronic diseases. The world’s population is rapidly aging with the number of individuals over 65 estimated to double by 2050 [1]. Several hurdles complicate the discovery and development of molecular biomarkers of aging. This includes the time required to age animals, the need to test large numbers of candidate markers, and the translation of tests between models and species. Mass-spectrometry based measures can examine thousands of candidate proteins from archived tissues www.aging‐us.com and bio-fluids, economically enabling discovery of new biomarkers. Proteomic measures facilitate analysis of numerous strains of mice, genetic models of aging and treatment groups relative to a reference population, to accelerate testing and validation of biomarkers. Mass spectrometry assays are based on the chemical measurement of specific amino acid sequences, not biological antibody recognition, allowing proteins to be tested across species with absolute molecular specificity

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