ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

Table 1

Selected ROS sensitive proteins that are involved in cell signaling transduction mechanism. Indicative examples of possible effects and processes they promote after being directly and/or indirectly modified by ROS (the references are indicated inside the square brackets).

ROS sensitive proteins: oxidative interface	() Effects of ROS sensitive proteins after being redox modified	() Physiopathological processes in which ROS sensitive proteins are involved
Protein kinases
Receptor/nonreceptor tyrosine kinases; (Src, TRK, AKT, c-Abl, MAPK, CaMKII, PKG, ATM, and Ask1)	(i) Interactions between kinases pathways [38, 39]; (ii) Signal of ROS production feedback [40]	Control of cell cycle progression [56]; Mitosis for anchorage-dependent cells [57]; Cellular homeostasis [43, 57]
AMP-activated protein kinases; (AMPK)	(i) Regulation of cell ROS/redox balance [41, 42]	Myocyte adaptation to energy requirement [42]; Adipocyte differentiation [58]; Lipid metabolism (“fatty liver”) [59]; Hyperglycemic damage [60]; Cell fate (autophagy and apoptosis) [61]
Adaptor proteins
p66Shc	(i) Signaling start in the aging process [43]	Apoptosis [43]. Prolonged life span [43, 62]; Cardiovascular diseases and obesity [63]; Diabetic endothelial dysfunction [64]
Nuclear receptors
PPARγ	(i) Redox sensor function [43]; (ii) Regulation of genes that modulate ROS increases [44]	Neurodegenerative diseases [65, 66]; Lipid dysfunction (fatty liver) [59]
Membrane receptors
Elements in Notch1 pathway	(i) Notch signaling modulation in association with Wnt/beta-catenin signal [45]	Cell fate control in vascular development [45]; Biological clocks in embryonic development [67]
Transcription factor
p53	Modulation of cell redox balance (prooxidant/antioxidant effects) [46–48]	Cell fate signaling [68]; Autophagy and apoptosis [61, 69]
Nrf2	Cell adaptation to ROS resistance [49, 50]	Apoptosis [70]; Neurodegenerative diseases [71]; Cardiovascular diseases [72]
FOXO3A	Cell coordination in response to OS [51]	Metabolic adaptation to low nutrient intake [73]; Cancer development [73]; Diabetes [74]; Atherosclerotic cardiovascular disease [75]
Components in β-catenin/Wnt pathway	Regulation of Wnt signaling via nucleoredoxin [76]	Early embryonic development [76]; Vascular development [45]
HIF-1a	Cell adaption to oxygen tension modifications [52]	Cell proliferation; angiogenesis [77]; Cell transformation [78, 79]
Components in JAK–STAT pathway	(i) Cell adaption to OS [53]; (ii) Mediation of ROS mitogenic effect [53]	Stress response gene expression [51]; Systemic/pulmonary hypertension [80]
NF-κB	Regulation of redox-sensitive gene expression; [54, 55]	Rheumatoid arthritis, dyslipidemia, atherosclerosis, and insulin resistance [81]