Cell Cycle

Publication Title: 
Seminars in Hematology

Hematopoietic stem cells (HSCs) have the immense task of supplying an organism with enough blood to sustain a lifespan. Much of what is known about how this scant population of cells can meet the varying demand of producing more than 10(11) cells per day comes from studies conducted in an animal that is a fraction of our size and lives roughly 1/30th of our lifespan. The differences in longevity can be expected to impose different demands on a cell essential for existence.

Author(s): 
Sykes, Stephen M.
Scadden, David T.
Publication Title: 
Radiation Research

FancD2 plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. Fancd2(-/-) mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in Fancd2(-/-) mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and radiosensitivity in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines.

Author(s): 
Berhane, Hebist
Epperly, Michael W.
Goff, Julie
Kalash, Ronny
Cao, Shaonan
Franicola, Darcy
Zhang, Xichen
Shields, Donna
Houghton, Frank
Wang, Hong
Wipf, Peter
Parmar, Kalindi
Greenberger, Joel S.
Publication Title: 
Deutsche Medizinische Wochenschrift (1946)
Author(s): 
Nikolaus, S.
Schreiber, S.
Publication Title: 
Experimental Gerontology

We describe a new chronological lifespan (CLS) assay for the yeast Schizosaccharomyces pombe. Yeast CLS assays monitor the loss of cell viability in a culture over time, and this new assay shows a continuous decline in viability without detectable regrowth until all cells in the culture are dead. Thus, the survival curve is not altered by the generation of mutants that can grow during the experiments, and one can monitor the entire lifespan of a strain until the number of viable cells has decreased over 10(6)-fold.

Author(s): 
Chen, Bo-Ruei
Runge, Kurt W.
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Here I overview the accompanying three reports on suppression of cellular senescence with inhibitors of mTOR, PI-3K and MEK. How can growth inhibitors suppress senescence? May these aging-suppressants decelerate organismal aging? To answer these questions, we need to reconsider the meaning of aging.

Author(s): 
Blagosklonny, Mikhail V.
Publication Title: 
Swiss Medical Weekly

The World Health Organization (WHO) assigns high priority to the prevention of non-communicable age-related diseases such as heart disease, cancer, diabetes, stroke and chronic lower respiratory diseases. They are now the leading causes of death, in both industrialised and developing countries, mostly due to increased life expectancy and urbanisation with associated changes in lifestyle and environment. Tobacco smoking, physical inactivity and resulting obesity are established risk factors for many chronic diseases.

Author(s): 
Probst-Hensch, N. M.
Publication Title: 
Aging

Caloric restriction, that is limiting food intake, is recognized in mammals as the best characterized and most reproducible strategy for extending lifespan, retarding physiological aging and delaying the onset of age-associated diseases. The aim of this mini review is to argue that p53 is the connection in the abilities of both the Sirt-1 pathway and the TOR pathway to impact on longevity of cells and organisms.

Author(s): 
Tucci, Paola
Publication Title: 
The Journal of Cell Biology

We identified and characterized a human orthologue of Rif1 protein, which in budding yeast interacts in vivo with the major duplex telomeric DNA binding protein Rap1p and negatively regulates telomere length. Depletion of hRif1 by RNA interference in human cancer cells impaired cell growth but had no detectable effect on telomere length, although hRif1 overexpression in S. cerevisiae interfered with telomere length control, in a manner specifically dependent on the presence of yeast Rif1p.

Author(s): 
Xu, Lifeng
Blackburn, Elizabeth H.
Publication Title: 
Cancer Research

The telomerase ribonucleoprotein is a promising target for cancer therapy, as it is highly active in many human malignancies. A novel telomerase targeting approach combines short interfering RNA (siRNA) knockdown of endogenous human telomerase RNA (hTer) with expression of a mutant-template hTer (MT-hTer). Such combination MT-hTer/siRNA constructs induce a rapid DNA damage response, telomere uncapping, and inhibition of cell proliferation in a variety of human cancer cell lines.

Author(s): 
Goldkorn, Amir
Blackburn, Elizabeth H.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Loss of the protective function of telomeres has previously been hypothesized to cause a DNA damage response. Here, we report a genome-wide expression response, the telomerase deletion response (TDR), that occurs when telomeres can no longer be maintained by telomerase. The TDR shares features with other DNA damage responses and the environmental stress response. Unexpectedly, another feature of the TDR is the up-regulation of energy production genes, accompanied by a proliferation of mitochondria.

Author(s): 
Nautiyal, Shivani
DeRisi, Joseph L.
Blackburn, Elizabeth H.

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