Free radicals (especially ROS, RNS, RSS, and RCS) are evolutionally archetypal, ubiquitous, and omnipotent in physiological and pathophysiological processes. Classical free-radical paradigm in aging and age-related pathologies, focused in essence on oxidative cellular damage, in order to resolve the problem of free radicals physiological-detrimental dichotomy, decipher genuine triggering mechanisms of aging, and grasp subtle molecular ways of intervention, needs new expansions, conceptualization, and generalization. Presented novel insights into free radicals dual immanent nature and environmentally effected functions in aging processes including aging brain and neurodegeneration, are based on original concepts of free radicals dynamic charge transfer (CT) (redox) chemical ambivalence (interactional philicity - nucleo-, electro-, and ambiphilicity spectrum); reactivity and selectivity in interactions with biological substrates; physiological functional ambivalence and complementarity, and dynamic free radical CT (redox) homeostasis. Subtle perturbations in free-radical redox homeodynamics, in responsive redox signaling networks, concomitant alterations in redox genes expression, transcription, and apoptosis, redox control of the mitochondrial ET chain, mitochondrial and steroids biogenesis, redox regulation of telomere/telomerase balance, DNA CT, proteins (mis)folding and molecular switches, circadian clock, hemispheric biochemical dominance, brain water and ions homeodynamics via aquaporins channels, dynamics of membranes permeability, neurotransmission, correlated brain/CNS/CVS response, etc, have more fundamental impact on aging processes than simple free radicals inflicted damage of cellular constituents which is also a consequence of perturbed free radicals dynamic homeostasis and their complementarity leading to production-elimination imbalance and oxidative and nitrosative stress with involvement of O-, N-, S-, and C-centered species. This expansion and conceptualization of free-radical paradigm may constitute new dimension in deciphering intimate molecular mechanisms and determining intervention pathways for subtle borderline norm-pathology dichotomy in aging, i.e., redoxomics, which involves investigation of free-radical, redox, and CT states of ROS, RNS, RSS, and RCS, DNA bases, their intermediates, interacting biological substrates and milieu, and penetrates and links genomics, proteomics, metabolomics, and chronomics including their epi-counterparts.
free-radical paradigm in aging
free radicals chemical and physiological ambivalence and complementarity
free-radical dynamic redox homeostasis