An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans

Abstract

While many diseases of aging have been linked to the immunological system, immune metrics with which to identify the most at-risk individuals are lacking. Here, we studied the blood immunome of 1001 individuals age 8-96 and derived an inflammatory clock of aging (iAge), which tracked with multi-morbidity and immunosenescence. In centenarians, iAge was on average, 40 years lower than their corresponding chronological age. The strongest contributor to this metric was the chemokine CXCL9, which was involved in cardiac aging, affected vascular function, and down-regulated Sirtuin-3, a longevity-associated molecule. Thus, our results identify an important link between inflammatory molecules and pathways known to govern lifespan.

Age-dependent and Independent Symptoms and Comorbidities Predictive of COVID-19 Hospitalization

“…It is possible that the older population was less likely to use a smartphone app, leading to under representations of the sick older population. The fact that age-associated variables outperform age in the prediction of patient hospitalization indicates that biological age or immunological age36,37 could be appropriate measures in assessing an individual's prognosis.In conclusion, we identify age-dependent and independent sets of symptoms and comorbidities predictive of COVID-19 patient hospitalization. Our analyses show features that predict disease severity in advance and this can be utilized to inform severe cases of COVID-19 even in younger individuals who may not be labeled as high risk.…”

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

“…Despite no standard cytokine signature exists in age‐related chronic inflammation in contrast to the acute inflammatory response, for which a number of secreted molecules have been validated, a deep‐learning based inflammatory aging (iAGE) clock has been recently created (Table S1, Supporting Information). [ 66 ] The clock is based on circulating immune protein data of 50 cytokines, chemokines, and growth factors, with the ability to predict multimorbidity with 0.41 mean absolute error. In centenarians, iAge was on average, 40 years lower than their corresponding chronological age, witch chemokine CXCL9 and down‐regulated Sirtuin‐3 as the strongest contributors.…”

The complex relationship between Immunosenescence and Inflammaging: Special issue on the New Biomedical Perspectives

“…In this scenario, "good" and "bad" aging, ARDs, and longevity represent a continuum without precise boundaries, the extremes being represented by the wide range of relatively "younger" people affected by overt mild or severe ARDs, where inflammation plays a major pathogenic role, and by centenarians-the best example of successful aging [10,11]-where inflammaging is present but at much lower level than younger people [12,13].…”

“…In centenarians inflammaging appears to be balanced (at least in part) by the upregulation of a variety of antiinflammaging parameters [14], and their "biological age" is significantly lower than their chronological age [13]. Moreover, centenarians show, at least in part, many characteristics similar to individuals who followed a calorierestricted diet, one of the best practices to delay aging [15].…”