A Top Aging Biomaker, the Science Behind C-Reactive Protein

Measuring and charting C-Reactive Protein (CRP) values is proving useful in diagnosing Covid 19 patients.

But CRP could also play a role as an important biomarker, not only for infections, but successful aging. CRP is both a first responder in acute infections, and elevated in low-grade inflammation.

During an infection white blood cells including macrophages and T cells release a pro-inflammatory protein involved in cell signaling called cytokine interleukin-6. The activation of the interlukin-6 protein, then causes a downstream rapid increase in CRP levels in the blood.

CRP is an “acute phase reactants”, and part of the first responder part of the immune system. CRP works in part by binging to a dead or dying cells, and clearing away these pathogens and dead tissue.

The half-life of C-reactive protein is short.

Due to its rapid response C-reactive protein levels can spike up to 10,000-fold in a matter of hours.

When it was first discovered in 1930, scientists thought this ring-shaped blood protein might be a pathogenic secretion since CRP protein is elevated in a variety of illnesses, including cancer.

The High Sensitivity C-Reactive Protein Biomarker in a Brief Timeline:

1993 – William Ershler, in his article “IL-6: A Cytokine for Gerontologists,” indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. IL-6 in human physiology and pathology has substantially grown. Low Vitamin-D, slower gait speed, and increase in Interlukin-6 are parameters studied in gerontology field. However, measuring Interlukin-6 levels was reserved for clinical trials, due to the expensive blood test.

Mid-1990s – In the mid 1990s, immunoassays for C-reactive protein (CRP), with greater sensitivity than those previously in routine use, revealed that increased CRP values, even within the range previously considered normal, strongly predict future coronary events. These findings triggered widespread interest, especially, remarkably, in the US, where the clinical use of CRP measurement had been largely ignored for about 30 years.

2002 – Data suggesting that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol roils. Scientists conducting a large population study in a New England Journal of Medicine 2002 found that many things can cause elevated CRP, making the blood test not a very specific prognostic indicator. But CRP deliver additive value at providing more information on risk for cardiovascular events than the LDL cholesterol level alone.

2009 – Upstream of C-Reactive protein, Interlukin-6 Serum (IL-6) levels are studied in the clinical setting by gerontology researchers. In a gerontology cohort case study (because of its activity across multiple physiological systems), Interlukin-6 Serum levels were found to predict frailty with aging. The IL-6 pathway is named a “gerontology biomarker” as it appears to be profoundly implicated in the pathophysiology of physical function decline and chronic diseases that often affect older persons.

2018 – C-reactive protein added as one of reliable biomarker of 9 aging biomarkers in a new biological age clock. The new biological age clock called DNAm PhenoAge, looks beyond tissue samples to include immune system function.

The nine biomarkers that identified “phenotypic age” included: albumin, creatine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count.h.

On the heels of Covid, hsCRP is coming into the spotlight and could be a multipurpose biomarker of successful aging.