Cell Proliferation

Publication Title: 
The EMBO journal

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.

Author(s): 
Gire, VÈronique
Roux, Pierre
Wynford-Thomas, David
Brondello, Jean-Marc
Dulic, Vjekoslav
Publication Title: 
Biochemical and Biophysical Research Communications

Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens progressively with cell division and limits the replicative potential of normal human somatic cells. L-carnosine, a naturally occurring dipeptide, has been reported to delay the replicative senescence, and extend the lifespan of cultured human diploid fibroblasts. In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells.

Author(s): 
Shao, Lan
Li, Qing-Huan
Tan, Zheng
Publication Title: 
Aging Cell

Fetal cardiomyocytes have been proposed as a potential source of cell-based therapy for heart failure. This study examined cellular senescence in cultured human fetal ventricular cardiomyocytes (HFCs). HFCs were isolated and identified by immunocytochemistry and RT-PCR. Cells were found to senesce after 20-25 population doublings, as determined by growth arrest, morphological changes and senescence-associated beta-galactosidase activity. Using the telomeric repeat amplification protocol assay, telomerase activity was undetectable in primary HFCs.

Author(s): 
Ball, Andrew J.
Levine, Fred
Publication Title: 
Journal of Cell Science

In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor beta (TGF-beta)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells.

Author(s): 
Kim, Soo-Hyun
Rowe, Janice
Fujii, Hideta
Jones, Rebecca
Schmierer, Bernhard
Kong, Byung-Whi
Kuchler, Karl
Foster, Douglas
Ish-Horowicz, David
Peters, Gordon
Publication Title: 
Aging Cell

This past decade has seen the identification of numerous conserved genes that extend lifespan in diverse species, yet the number of compounds that extend lifespan is relatively small. A class of compounds called STACs, which were identified as activators of Sir2/SIRT1 NAD+-dependent deacetylases, extend the lifespans of multiple species in a Sir2-dependent manner and can delay the onset of age-related diseases such as cancer, diabetes and neurodegeneration in model organisms.

Author(s): 
Yang, Hongying
Baur, Joseph A.
Chen, Allen
Miller, Christine
Adams, Jeffrey K.
Kisielewski, Anne
Howitz, Konrad T.
Zipkin, Robert E.
Sinclair, David A.
Publication Title: 
Aging Cell

Dyskeratosis congenita (DC), an inherited bone marrow failure syndrome, is caused by defects in telomerase. Somatic cells from DC patients have shortened telomeres and clinical symptoms are most pronounced in organs with a high cell turnover, including those involved in hematopoiesis and skin function. We previously identified an autosomal dominant (AD) form of DC that is caused by mutations in the telomerase RNA component (TER).

Author(s): 
Westin, Erik R.
Chavez, Elizabeth
Lee, Kimberly M.
Gourronc, Francoise A.
Riley, Soraya
Lansdorp, Peter M.
Goldman, Frederick D.
Klingelhutz, Aloysius J.
Publication Title: 
Spine

STUDY DESIGN: Nonviral transfection of nucleus pulposus cells with a telomerase expression construct to assess the effects on cellular lifespan, function, karyotypic stability, and transformation properties. OBJECTIVES: To investigate whether telomerase gene therapy can extend the cellular lifespan while retaining functionality of nucleus pulposus cells in a safe manner. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc is an age-related condition in which cells responsible for the maintenance and health of the disc deteriorate with age.

Author(s): 
Chung, Sylvia A.
Wei, Ai Qun
Connor, David E.
Webb, Graham C.
Molloy, Timothy
Pajic, Marina
Diwan, Ashish D.
Publication Title: 
PloS One

Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals.

Author(s): 
Allard, Joanne S.
Heilbronn, Leonie K.
Smith, Carolina
Hunt, Nicole D.
Ingram, Donald K.
Ravussin, Eric
Pennington CALERIE Team
de Cabo, Rafael
Publication Title: 
Biogerontology

The premature ageing ataxia telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing. Young WS fibroblasts have an aged appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor SB230580 extends their lifespan to within the normal range. SB203580 also extends the replicative lifespan of normal adult dermal fibroblasts, however, the effect is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo a form of stress-induced premature senescence (SIPS).

Author(s): 
Davis, Terence
Kipling, David
Publication Title: 
Biogerontology

The replicative lifespan of many cell types is determined by the length of telomeres in the initiating cell population. In 20% oxygen, IMR90 cells have a shorter replicative lifespan compared to that achieved in conditions that lower the levels of oxidative stress. We sought to address the role of telomere dynamics in determining the replicative lifespan of IMR90 cells. We analysed clonal populations cultured in parallel in 3 and 20% oxygen. We observed that, at senescence, telomere length was shorter in 3% oxygen and this was proportional to the lifespan extension.

Author(s): 
Britt-Compton, Bethan
Wyllie, Fiona
Rowson, Jan
Capper, Rebecca
E Jones, Rhiannon
M Baird, Duncan

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