Neurohormesiomics

Neurohormesiomics

Definition

Neurohormesiomics is the systematic, omics-scale study of hormetic phenomena occurring within and mediated by the nervous system — the biphasic, concentration-dependent adaptive responses through which neurons, glial cells, and neural circuits sense, transduce, and benefit from sub-threshold stress stimuli — and their comprehensive molecular consequences across the neuro-genome, neuro-transcriptome, neuro-proteome, neuro-metabolome, and neuro-epigenome. It holds as its central premise that the nervous system is an exquisitely concentration-sensitive hormetic organ whose adaptive plasticity, cognitive resilience, neuroprotective capacity, and longevity are fundamentally governed by the quantitative parameters of neuronal stress exposure. Neurohormesiomics maps the full molecular architecture of neural hormetic signaling networks at omics resolution, integrating neurotranscriptomic, neuroproteomic, neurometabolomic, and connectomic data to construct a systems-level understanding of how calibrated neuronal stress drives beneficial adaptive reprogramming across the brain, peripheral nervous system, and neuroendocrine axes.

Core Principle

The foundational postulate of Neurohormesiomics is: calibrated neuronal stress, operating within the hormetic zone, is a primary driver of synaptic plasticity, cognitive resilience, neuroprotection, and neural longevity. The nervous system occupies a uniquely vulnerable yet uniquely adaptive position within the organismal hormetic landscape: neurons are among the most metabolically demanding, oxidatively stressed, and long-lived cells in the body, and consequently among the most exquisitely sensitive to the quantitative parameters of stress exposure. Neurohormetic signals — including neurotrophic factors, glutamate, cortisol, reactive oxygen species, heat shock proteins, and inflammatory cytokines — operate across steep biphasic concentration-response gradients in which the difference between neuroprotection and neurodegeneration is determined not by the identity of the signal but by its concentration, timing, and duration.

Scope

Neurohormesiomics encompasses:

• Neurotrophic factor hormesiomics: omics-scale characterization of the biphasic, concentration-dependent effects of neurotrophic factors — including BDNF, NGF, GDNF, VEGF, and IGF-1 — on neuronal survival, synaptic plasticity, dendritic arborization, and cognitive function, with particular attention to age-associated decline in neurotrophic concentrations within the aging Dosagiome.
• Glutamate hormesiomics: systematic mapping of the concentration-dependent biphasic effects of glutamatergic signaling — neuroprotective and synaptogenic at physiological concentrations, excitotoxic and neurodegenerative at supraphysiological concentrations — across transcriptomic and proteomic layers in neuronal populations.
• Neuroinflammatory hormesiomics: omics-resolution characterization of the biphasic regulatory roles of neuroinflammatory mediators — including TNF-α, IL-6, IL-1β, and microglial activation states — whose low-concentration signaling supports synaptic pruning, neuroprotection, and cognitive function, and whose high-concentration, chronic elevation drives neurodegeneration and accelerated brain aging.
• Cognitive hormesiomics: systematic, multi-omics investigation of how cognitively challenging experiences — learning, environmental enrichment, controlled psychological stress — function as hormetic stimuli activating neuroprotective transcriptional programs, epigenetic remodeling, and synaptic strengthening across the neural connectome.
• Aging neurohormesiomics: characterization of the progressive erosion of neural hormetic competence with age — the blunting of BDNF responses, the narrowing of the neuroprotective hormetic window, the shift from adaptive to maladaptive neuroinflammation, and the accumulation of proteotoxic aggregates — as a central mechanism driving age-related cognitive decline and neurodegenerative disease.
• Pharmacological neurohormesiomics: omics-resolution mapping of the concentration-dependent neurohormetic effects of neuroprotective and cognitive-enhancing compounds — including lithium, rapamycin, resveratrol, spermidine, and BDNF mimetics — providing a quantitative foundation for precision neurohormetic intervention strategies targeting neurodegeneration and brain aging.
• Neuroendocrine hormesiomics: systematic characterization of biphasic concentration-response landscapes of neuroendocrine hormones — including cortisol, estrogen, testosterone, DHEA, melatonin, and growth hormone — across neural and systemic omics layers, with particular focus on the age-associated dysregulation of neuroendocrine dosage landscapes.

Neurohormesiomics resolves a central and clinically consequential paradox of neuroscience: that the same molecular signals mediating neuronal survival, synaptic plasticity, and cognitive enhancement at physiological concentrations drive neurodegeneration, excitotoxicity, and cognitive decline at supraphysiological or chronically elevated concentrations. By situating neural biology within a unified concentration-resolved hormetic framework, Neurohormesiomics provides the mechanistic foundation for understanding why many neuroprotective interventions fail in clinical translation — where the hormetic window of efficacy is routinely exceeded — and supplies the quantitative principles necessary for the rational design of concentration-calibrated neural longevity interventions.

Coined by

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