Cellular responses to reactive oxygen species-induced DNA damage and aging.
Oxidative stress in cells and tissues can occur during pathophysiological developments, e.g., during inflammatory and allergic diseases or during ischemic or toxic and hyperglycemic conditions via the generation of reactive oxygen species (ROS). Moreover, ROS can be generated by radiation (UV, X-rays) and pharmacologically, e.g., by anthracyclins as chemotherapeutic compounds for treatment of a variety of tumors to induce 'stress or aberrant signaling-inducing senescence' (STASIS). Although STASIS is distinguished from intracellular replicative senescence, a variety of cellular mechanisms appear similar in both aging pathways. It is generally accepted that oxidative stress and ROS eventually cause DNA damage, whereby insufficient cellular repair mechanisms may contribute to premature aging and apoptosis. Conversely, ROS-induced imbalances of the signaling pathways for metabolic protein turnover may also result in opposite effects to recruit malfunctioning aberrant proteins and compounds that trigger tumorigenic processes. Consequently, DNA damage plays a role in the development of carcinogenesis, but is also associated with an aging process in cells and organisms.
Bertram
Catharina
C
Department of Gynecology (OE 6411), Medical School Hannover, D-30625 Hannover, Germany.
Hass
Ralf
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism / Q000502:physiology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D000076105:X-ray Repair Cross Complementing Protein 1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019098:Telomerase