Novel Omics Assessments of the Burden of Age-Related Inflammation Correlate with Mortality Risk
The chronic inflammation of aging is harmful to health, the result of accumulating senescent cells, maladaptive reactions to molecular damage characteristic of aging, and other similar problems. While short-term inflammation is useful and necessary to defense against pathogens, elimination of potentially cancerous damaged cells, and regeneration from injury, unresolved, constant inflammatory signaling is disruptive to tissue structure and function. It changes cell behavior for the worse throughout the body. The immune system is complex, and so is inflammatory signaling. There are many possible ways to measure inflammation, and most have some dependency on the broader context of the state of the body, specific medical condition, and so forth. As researchers demonstrate here, it is quite possible to depart from the usual measures to produce novel and potentially better assessments of the contribution of inflammation to mortality based on omics data.
Inflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (Polygenic-Risk-Score; PRS), metabolomics (Metabolomic-Risk-Score; MRS), and epigenetics (Epigenetic-Risk-Score; ERS) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa).
We found that multi-omics risk-scores generally outperformed single-omics risk scores in prediction of all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher hazard ratio (HR) per standard deviation (SD) increase for all cause-mortality when including both score and circulating IL6 in the same model (1-SD IL6 MRS-ERS: HR=1.77 vs. 1-SD circulating IL6 HR=1.11; 1-SD IL6 PRS-MRS: HR=1.32 vs. 1-SD circulating IL6 HR=1.31; 1-SD PRS-MRS-ERS: HR=1.62 vs. 1-SD circulating IL6: HR=1.16).
In the Nurses' Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1-SD of IL6 PRS and 1-SD IL6 PRS-MRS had HR=1.13 and HR=1.13, among individuals older than 65years without mutual adjustment of the score and circulating IL6. Our study demonstrated that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for aging process and lifespan.