| Affiliation: | 1. Department of Molecular Medicine, Center on Aging, The Scripps Research Institute, Jupiter, FL, USA;2. Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN, USA;3. Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN, USA;4. Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA;5. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA;6. Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA;7. Department of Pathology, University of Washington, Seattle, WA, USA;8. Department of Comparative Medicine, University of Washington, Seattle, WA, USA |
| 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 Bubr1H/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. |
