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

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.