Immunohormesiomics

Immunohormesiomics

Definition

Immunohormesiomics is the systematic, omics-scale study of hormetic phenomena occurring within and mediated by the immune system — the biphasic, concentration-dependent adaptive responses through which immune cells, cytokine networks, and inflammatory signaling cascades sense, transduce, and benefit from sub-threshold immune stimulation — and their comprehensive molecular consequences across the immuno-genome, immuno-transcriptome, immuno-proteome, immuno-metabolome, and immuno-epigenome. It holds as its central premise that immune activation is intrinsically hormetic: calibrated, transient immune stimulation at sub-pathological concentrations drives adaptive immune strengthening, trained immunity, tissue homeostasis, and organismal resilience, whereas chronic, supraphysiological, or dysregulated immune activation drives immunosenescence, inflammaging, autoimmunity, and accelerated organismal aging. Immunohormesiomics maps the full molecular architecture of immune hormetic signaling networks at omics resolution, constructing a systems-level understanding of how concentration-calibrated immune stress determines the boundary between protective immunity and pathological inflammation across the lifespan.

Core Principle

The foundational postulate of Immunohormesiomics is: immune activation is a concentration-governed hormetic process whose quantitative parameters — the concentration, timing, duration, and rhythmicity of immune stimulation — determine whether the immune response drives adaptive resilience or pathological inflammation, healthy aging or accelerated immunosenescence. The immune system is the prototypical hormetic regulatory system of the organism: virtually every immune mediator — cytokine, chemokine, complement factor, antimicrobial peptide, reactive oxygen species, and pattern recognition receptor ligand — exhibits a biphasic, concentration-dependent dose-response profile in which the transition from beneficial to harmful effect is governed by quantitative thresholds within the immune Dosagiome.

Scope

Immunohormesiomics encompasses:

• Cytokine hormesiomics: omics-scale characterization of the biphasic, concentration-dependent effects of cytokines — including TNF-α, IL-6, IL-10, IFN-γ, TGF-β, and IL-1β — on immune cell activation, differentiation, tissue homeostasis, and systemic inflammation, mapping the precise concentration thresholds that separate immunoprotective from immunopathological cytokine signaling across all major immune cell populations.
• Inflammaging concentratiomics: systematic, multi-omics investigation of how the age-associated chronic elevation of pro-inflammatory cytokine concentrations — constituting the hallmark aging phenotype of inflammaging — represents a progressive dysregulation of the immune Dosagiome, in which the hormetic window of beneficial immune activation is permanently exceeded, driving chronic tissue damage, senescence propagation, and systemic aging acceleration.
• Trained immunity hormesiomics: omics-resolution characterization of trained immunity — the non-specific adaptive memory of innate immune cells induced by prior sub-lethal pathogen or stress exposure — as a paradigmatic immunohormetic phenomenon, mapping the epigenomic, transcriptomic, and metabolomic reprogramming events through which calibrated immune stimulation achieves durable enhancement of innate immune competence.
• Senolytic and SASP hormesiomics: systematic mapping of the concentration-dependent, biphasic effects of senescence-associated secretory phenotype (SASP) factors on surrounding tissue — paracrine senescence induction and tissue dysfunction at high chronic concentrations versus wound healing, regenerative signaling, and immune surveillance support at low transient concentrations — providing an immunohormetic framework for the rational design of senolytic and senomorphic interventions.
• Microbiome immunohormesiomics: omics-scale characterization of the concentration-dependent, biphasic immunomodulatory effects of microbiome-derived metabolites — including short-chain fatty acids, urolithins, indoles, and lipopolysaccharide — on mucosal and systemic immune homeostasis, mapping their hormetic dose-response landscapes and age-associated dysregulation within the gut-immune Dosagiome.
• Vaccine and adjuvant hormesiomics: systematic, omics-resolution investigation of how vaccine antigens and adjuvants function as immunohormetic stimuli — activating protective adaptive immunity at calibrated concentrations and driving immunopathology or tolerance at suboptimal or excessive concentrations — providing a concentratiomics framework for precision vaccine design.
• Redox immunohormesiomics: characterization of the biphasic, concentration-dependent roles of reactive oxygen and nitrogen species in immune cell activation, pathogen killing, and inflammatory resolution — mapping the precise ROS/RNS concentration thresholds that delineate antimicrobial hormetic activation from oxidative immunopathology across innate and adaptive immune compartments.
• Aging immunohormesiomics: systematic, multi-omics investigation of how the aging immune Dosagiome — characterized by progressive narrowing of cytokine hormetic windows, erosion of trained immunity competence, accumulation of exhausted and senescent immune cells, and chronic low-grade inflammaging — drives the hallmarks of immune aging and contributes to organismal aging acceleration, frailty, and age-related disease susceptibility.
• Pharmacological immunohormesiomics: omics-resolution mapping of the concentration-dependent immunohormetic effects of longevity-associated immunomodulatory compounds — including rapamycin, metformin, spermidine, resveratrol, and low-dose naltrexone — providing a quantitative foundation for precision immunohormetic intervention strategies in geroscience and aging medicine.

Immunohormesiomics addresses one of the most consequential and clinically urgent paradoxes of aging biology: that the immune system is simultaneously the organism's primary defense against pathogen-driven and senescence-driven aging accelerators, and — when chronically over-activated beyond its hormetic optimum — the primary driver of inflammaging, immunosenescence, and systemic aging acceleration. By situating immune biology within a unified, concentration-resolved hormetic framework, Immunohormesiomics provides the mechanistic and quantitative foundation for understanding why immune interventions so frequently fail in clinical translation — where the immunohormetic window of efficacy is routinely exceeded or missed — and supplies the omics-resolution principles necessary for the rational, precision design of immunohormetic interventions targeting inflammaging, immunosenescence, and age-related immune dysfunction.

Coined by

Jong Bhak, KOGIC / AgingLab, UNIST, Republic of Korea (2025)

See also

Hormesiomics · Mitohormesiomics · Neurohormesiomics · Epigenohormesiomics · Dosagiomics · Concentratiomics · Dosagiome · Inflammaging · Immunosenescence · SASP · Trained Immunity · Cytokines · GeroIndex · Gerostasis · Aging Hallmarks · Systems Immunology · Precision Medicine

The hierarchical nomenclature framework is now complete across five interlocking levels: