MCP-1 as a Potential Biomarker of Biological Age

Researchers here add one more correlation between blood biochemistry and aging to the growing list. The greater the number of simple measures that can be associated with age-related decline, the more likely it is that researchers can find an algorithmic combination of those measures that quite accurately reflects biological age. At the moment epigenetic clocks based on assessment of DNA methylation patterns are leading the pack of potential biomarkers of aging because they are in effect a combined set of smaller measures, those being made by the cells themselves. Many specific DNA methylation changes are reactions to the cellular damage and dysfunction of aging. However, other approaches to combining measures of aging and cellular reactions may turn out to be better in the end. We shall see in the years ahead.

Generally agreed upon, robust, cheap, and reliable biomarkers of aging are important because they will greatly accelerate the pace of development in aging research. Currently the field lacks a good, rapid way to assess the outcome of a potential intervention to slow or reverse the aging process. The only widely accepted approach is to carry out life span studies, and that means that any sort of debate over viability or quality or strategy will drag on for years, and cost millions that might have been invested elsewhere. Mouse life span studies are not cheap. If the field is instead equipped with an assessment of biological age that can run immediately before and immediately after a treatment, then exploration and validation in aging research will become far more rapid and far less costly. The best approaches, most likely something along the lines of the SENS damage repair strategy, will win out more rapidly.

Aging is the major risk factor for numerous chronic diseases and is responsible for the bulk of healthcare costs. To address this healthcare crisis, there is a growing interest in identifying ways to therapeutically target aging in order to prevent, delay, or attenuate multiple age-related diseases simultaneously. A number of therapeutic strategies have emerged. However, a major barrier to clinical trials targeting aging is the prolonged time between intervention and clinical outcomes. For these studies, surrogate endpoints will dramatically improve the economy and timescale in which we can measure the effects of interventions on biological age.

Biological age is defined by the health or fitness of an individual, and lack of age-related diseases, irrespective of their chronological age. Biological age can be quite distinct from chronological age. For example, cancer survivors are biologically older than their chronological age due to exposure to genotoxic agents, while centenarians are frequently biologically younger than their chronological age. A biomarker of biological age in accessible bodily fluids or tissues would be extremely valuable for clinical trials testing antigeronic factors, but also potentially for triaging patients facing onerous therapeutic procedures. Hundreds of studies have aimed to discover age-related changes in circulating factors including metabolites, advanced glycation end-products, exosome content, miRNA, and inflammatory molecules, with varying success.

Here, we identified MCP-1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating 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.

Link: https://doi.org/10.1111/acel.12706

Comments

One of the most significant advances in aging knowledge in the past decade is that old blood has a number of peptides that are found at increasing levels as people age. A strong focus of aging research should be to find a good biomarker to measure this source of aging, and also, to put in place methods to treat it. As suggested in the article, these old blood molecules could be treated by pharmaceuticals or by genetic means. Perhaps there are other methods/interventions that could be taken as well. It might even be practical to encourage over activation of the kidneys to filter out the age causing peptides in the blood stream. Every effort should be made to address this cause of aging.

Posted by: Biotechy at January 8th, 2018 6:38 AM

Note how the researchers tested D&Q the senolytic combo and noted the significant reduction of MCP-1 levels.

Posted by: Steve Hill at January 10th, 2018 7:33 AM

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