Multiomics Quantification of Immune Resilience: Engineering Healthspan Across Diverse Disease Contexts
We investigate salutogenesis-the active creation of health-through blood-based multiomics signatures quantifying Immune Resilience (IR). Our prior work demonstrated that TCF7-centered signatures predict 15-year survival advantages independently of age, with 40-year-olds showing degraded IR facing mortality risk equivalent to 55-year-olds with optimal IR. These findings reveal stable biological programs linking immune-inflammatory balance to disease resistance before pathology emerges.
Research Questions:
1. Can multiomics biomarkers distinguishing optimal IR prospectively predict healthspan across diverse disease contexts: severe infections (influenza, HIV progression), inflammatory diseases (allergic asthma, obesity), cardiovascular disease, neurodegenerative disorders (Alzheimer’s, dementia), metabolic conditions, and rare diseases capturable only in large cohorts?
2. What genetic determinants and modifiable factors (GLP-1 therapies, microbiome-focused diets, physical activity regimens) govern maintenance versus degradation of optimal IR throughout the lifespan?
3. Which IR-related molecular pathways and brain-immune axis connections represent therapeutic targets for extending disease-free survival?
Scientific Rationale: Current research focuses on pathogenic mechanisms (inflammaging, immunosenescence, cellular senescence). We propose IR counters these aging drivers through coordinated programs linking immunocompetence, inflammation control, physical performance, and behavioral traits. UK Biobank’s unparalleled datasets enable validation across: transcriptomic profiles (gene expression signatures predicting longevity, disease resistance, interferon pathways); proteomics (biomarker discovery for metabolic health, immunocompetence); genomics (genetic determinants of disease susceptibility); flow cytometry and cytokine panels (mechanistic validation).
