This intriguing finding suggests that NER deficiency is not life-span limiting in post-mitotic tissue and that a postulated DNA-damage-induced SR even extends life span, together with reduced insulin signaling.
Liver was selected for this analysis because as the central metabolic organ of the body it is a major target of oxidative DNA damage, a postulated cause of aging, and suffers from some prominent aging-related pathology [11].
It is known that proteinuria induces signals for tubulointerstitial inflammation and activates fibrogenic pathways as a postulated mechanism of kidney damage [ 24].
However, excessive or misplaced production leads to host tissue damage, with this postulated to contribute to a number of inflammatory diseases, including atherosclerosis, asthma, rheumatoid arthritis, cystic fibrosis and some cancers (reviewed in [ 1, 3]).
It is further postulated that these cause oxidative damage to the cellular mitochondria and to mitochondrial DNA, which is most susceptible to this oxidative stress (Liang and Godley 2003).
However, our mouse and HCT116 data also show that Caspase-2 is not strictly required for cell death under these conditions, which is consistent with earlier studies in mice and human cancer cells that failed to support a proapoptotic role of the postulated PIDDosome complex after DNA damage.
The scheme does not directly point to the damage location but, given a postulated distribution, computes a metric that (for ideal conditions) approaches infinity when the distribution is correct.
We hypothesize that chronic exposure to environmental toxicants can induce genetic damage causing DNA repair deficiencies and leading to the postulated mutator phenotype of carcinogenesis.
Reactive oxygen species have been shown to influence both normal chondrocyte activity and cartilage damage [ 9] so an important role for antioxidants is widely postulated [ 10].
The central role of plasma membrane damage in the genesis of irreversible cell injury is used to divide the postulated roles for calcium ions into two major mechanisms.
