Normal human fibroblasts in culture have a limited lifespan, ending in replicative senescence. Introduction of SV40 sequences encoding large T antigen and small t antigen into pre-senescent cells results in an extension of lifespan for an additional 20-30 population doublings.
Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway.
Extension of the storage period of apheresis platelets to seven or ten days may be possible with the implementation of screening for bacteria. This, however, may impair platelet quality, and additive compounds that improve storage parameters would be desirable. Apheresis platelets were harvested using the Cobe LRS device. Part of the product was aliquoted into two CLX bags, 60 ml into each, on day 0. L-carnitine (LC) to a final concentration of 5 mM was added to one container and saline to the other.
Evolutionary theory has guided the development of antiaging interventions in some conscious and some unconscious ways. It is a standard assumption that the body's health has been optimized by natural selection, and that the most benign and promising medical strategies should support the body's efforts to maintain itself. The very concept of natural healing is a reflection of evolutionary thinking about health.
The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. The mammalian homologue of Sir2 (SirT1) regulates p53, NF-kappaB and Forkhead transcription factors, and is implicated in stress response. This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.
FOXO (Forkhead box O) transcription factors constitute an evolutionally conserved subgroup within the large Forkhead family of transcription regulators. FOXO factors are important regulators of the cell cycle, apoptosis, DNA repair, metabolism, oxidative stress resistance and longevity. Genetic studies of Caenorhabditis elegans demonstrated that FOXO factors are major targets of the insulin-like signalling implicated during the regulation of glucose metabolism and lifespan extension.
Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined.
FKHRL1 is one of the human homologues of DAF-16, which is concerned with longevity in Caenorhabditis elegans. Previously, we demonstrated that FKHRL1 functions downstream of Akt in erythropoietin (EPO) signaling and that it is directly phosphorylated by activated Akt. Because phosphorylated FKHRL1 loses its transcriptional activity and translocates into the cytoplasm, FKHRL1 appears to be nonfunctional in the presence of EPO.
It has been widely reported that CHO cells undergo apoptosis in culture, despite supplementation of nutrients through fed-batch strategies. Improvement of cell viability in culture can effectively improve recombinant protein yield through extension of the culture's production lifespan, especially at high cell densities. Heat shock proteins (HSPs) have been reported to demonstrate anti-apoptotic effects against a wide range of physical and chemical stimuli through their ability to bind and act as antagonists to critical apoptotic molecules.
Neutrophils are major cells participants in innate host responses. They are short-lived leukocytes, although microbial products activate intracellular signaling cascades that prolong their survival by inhibiting constitutive apoptosis. To gain insight into the phylogeny of this important cell type, we examined the ability of toll-like receptor agonists to extend the lifespan of gilthead seabream (Sparus aurata L.) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils.