Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans

Matthew J. Yousefzadeh, Marissa J. Schafer, Nicole Noren Hooten, Elizabeth J. Atkinson, Michele K. Evans, Darren J. Baker, Ellen K. Quarles, Paul D. Robbins, Warren C. Ladiges, Nathan K. LeBrasseur, Laura J. Niedernhofer

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early-onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP-1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein-1 (MCP-1) levels increased in an age-dependent manner in wild-type (WT) mice. That age-dependent increase was accelerated in Ercc1 −/Δ and Bubr1 H/H mouse models of progeria. Genetic and pharmacologic interventions that slow aging of Ercc1 −/Δ and WT mice lowered serum MCP-1 levels significantly. Finally, in elderly humans with aortic stenosis, MCP-1 levels were significantly higher in frail individuals compared to nonfrail. These data support the conclusion that MCP-1 can be used as a measure of mammalian biological age that is responsive to interventions that extend healthy aging.

Original languageEnglish (US)
Article numbere12706
JournalAging cell
Volume17
Issue number2
DOIs
StatePublished - Apr 2018

Bibliographical note

Funding Information:
This work was supported by NIH/NIA P01 AG043376 (LJN & PDR), NIH/NIA R24 AG047115 (WCL), NIH/NIA R01 AG038550 (EKQ, PI Rabinovitch), NIH/NIA T32 AG000057 (EKQ, PI Horton), NIH/NIA AG052958 and AG053832 (NKL). NNH and MKE are supported by the National Institute of Aging Intramural Research Program, National Institutes of Health (AG000519). We are grateful to Sara McGowan, Luise Angelini, Alexshiandria Ingle, and the Scripps Florida Animal Research Center for help with animal care. We gratefully acknowledge the contributions of the Geropathology Grading Committee for validating the composite lesion scores. We thank Nathan Foster for statistical consultation.

Funding Information:
NIH/NIA, Grant/Award Number: P01 AG043376, R24 AG047115, R01 AG038550, T32 AG000057, AG052958, AG053832; National Institute of Aging Intramural Research Program (AG000519), National Institutes of Health

Publisher Copyright:
© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • CCL2
  • biological age
  • biomarkers of aging
  • chemokine
  • geropathology
  • monocyte chemoattractant protein-1

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