Possible role of NF-κB in hormesis during ageing.

Hormesis in ageing is probably represented by mild stress-induced stimulation of protective mechanisms in cells and organisms resulting in biologically beneficial effects. Mild stress and hormetins may act on bifurcation points in the complex network of cell signaling and transcription factors, often turning homeodynamics to health or survival. Several signaling pathways activated by diverse stimuli and by stress response converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. NF-κB behaves as a chaotic oscillator and it is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. NF-κB is closely related to other important upstream signaling networks, creating chaotic oscillators with other receptor-related kinases and targeting hubs for hormesis. The great bulk of natural hormetins acts on these signaling pathways, while NF-κB appears as a key regulatory factor in this context. Due to its tight relationship with main signaling system NF-κB plays a fundamental role in stress response, apoptosis and autophagy and appears to be a possible target for hormesis in ageing.