The work presented here suggests another mechanism by which telomerase deficient cells that enter crisis may suffer increased rates of spontaneous genome rearrangement that can, perhaps, lead to cancer. However, this work suggests that telomerase also promotes genome rearrangements by DSB repair. This could have a significant impact on the response of tumor cells to radiation and chemotherapy, as many tumors reactivate the expression of telomerase, and these treatments generateDSBs in mammalian cells. Careful consideration of the multiple ways in which telomerase influences genome stability may, therefore, facilitate better prevention, diagnosis and treatment of cancer. Most patients with persistent sepsis develop multiple organ failure, a syndrome in which several organ systems are malfunctioning. In order for these patients to survive their vital organs need to be supported in the hospitals intensive care unit. Septic patients treated in the intensive care unit develop skeletal muscle dysfunction which is part of the multiple organ failure syndrome, and this persists after ICU Lomitapide Mesylate discharge. The nature of this muscle dysfunction includes weakness due to a severe loss of muscle mass and muscle fatigue which is most apparent during weaning of the mechanical ventilation and Pancuronium dibromide results in impaired physical capacity during the patient��s protracted recovery process. In addition to the long term failure of skeletal muscle function, rapid degeneration in the ICU also impacts on patient acute energy metabolism and this directs the need for concurrent interventions, such as insulin and glucocorticoid therapy, which are principally aimed at improving patient survival. In a previous study we demonstrated that mitochondrial content was 30�C40% lower and cellular adenine nucleotide homeostasis disrupted in skeletal muscle of ICU patients suffering from sepsis induced multiple organ failure. Mitochondria are the major mechanism for ATP generation in humans and the observed lower mitochondrial content and cellular energy status will accelerate muscle fatigue and possibly cell death in these septic patients. Indeed, mitochondrial derangements and the subsequent disruption in 
energy metabolism are associated with multiple organ failure and an increased mortality in critically ill patients. In addition, several animal models of sepsis and critical illness have shown mitochondrial derangements in skeletal muscle and other tissues confirming the generality of these observations. Skeletal muscle phenotype and mitochondrial content depend on the coordinated expression of nuclear and mitochondrial encoded genes, as well as the synthesis and degradation of proteins to maintain normal muscle function. Mitochondrial protein synthesis and degradation have to be in equilibrium in order for the cell to maintain a constant number of well functioning mitochondria. In this study we hypothesize that the lower mitochondrial content, we found in skeletal muscle of septic patients, is caused by a lower mitochondrial protein synthesis and this would be regulated by lower mitochondrial gene expression. Thus, we examined in vivo mitochondrial protein synthesis in skeletal muscle of patients treated in the ICU for sepsis induced MOF and compared this to age matched control subjects. Targeted analysis of gene expression of mitochondrial oxidative phosphorylation enzymes, mitochondrial proteases and master transcriptional regulators of mitochondrial biogenesis presented us with a complex picture.