Telomerase

Publication Title: 
Journal of Cellular Physiology

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.

Author(s): 
Macera-Bloch, Lisa
Houghton, JeanMarie
Lenahan, Melanie
Jha, Krishna K.
Ozer, Harvey L.
Publication Title: 
Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders: Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases

INTRODUCTION: The aim of this study was to determine the effect of hNT neuron transplants on motor neuron function in SOD1 (G93A) mice when motor deficits were already apparent. METHOD: The hNT neurons were implanted into L(4)-L(5) segments of the ventral horn spinal cord of mice at 15-16 weeks of age: either G93A mice, transgenic mice carrying the normal allele for human SOD1 gene (hTg), or control wild type mice (wt). Behavioral tests (rotorod, beam balance, extension reflex, footprint) were performed prior to transplantation and at weekly intervals afterwards.

Author(s): 
Garbuzova-Davis, S.
Willing, A. E.
Milliken, M.
Saporta, S.
Sowerby, B.
Cahill, D. W.
Sanberg, P. R.
Publication Title: 
The EMBO journal

The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation.

Author(s): 
Langley, Emma
Pearson, Mark
Faretta, Mario
Bauer, Uta-Maria
Frye, Roy A.
Minucci, Saverio
Pelicci, Pier Giuseppe
Kouzarides, Tony
Publication Title: 
International Journal of Oncology

Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency relative to controls, while remaining contact-inhibited and maintaining a p53-mediated damage response following gamma-irradiation.

Author(s): 
Forsythe, Heidi L.
Elmore, Lynne W.
Jensen, Keith O.
Landon, Melissa R.
Holt, Shawn E.
Publication Title: 
Ageing Research Reviews

Aging is a universal biological phenomenon in eukaryotes, but why and how we age still remain mysterious. It would be of great biological interest and practical importance if we could uncover the molecular mechanism of aging, and find a way to delay the aging process while maintaining physical and mental strengths of youth. Histone deacetylases (HDACs) such as SIR2 and RPD3 are known to be involved in the extension of lifespan in yeast and Caenorhabditis elegans.

Author(s): 
Chang, Karen T.
Min, Kyung-Tai
Publication Title: 
Biogerontology

P. anserina mutants with impairments in complex IV (COX) of the respiratory chain are characterized by an increase in lifespan. Examples are the nuclear grisea mutant with a moderate lifespan extension (60%) and the immortal extranuclear ex1 mutant. Here we report data demonstrating that in mutant ex1 the level of the alternative oxidase (PaAOX) is significantly higher than in mutant grisea. PaAOX levels appear to be reversely dependent on COX activity.

Author(s): 
Borghouts, Corina
Scheckhuber, Christian Q.
Werner, Alexandra
Osiewacz, Heinz D.
Publication Title: 
Oncogene

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.

Author(s): 
Morris, Mark
Hepburn, Peter
Wynford-Thomas, David
Publication Title: 
International Journal of Radiation Oncology, Biology, Physics

PURPOSE: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. METHODS AND MATERIALS: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol.

Author(s): 
Wazer, David E.
Berle, Lisa
Graham, Roger
Chung, Maureen
Rothschild, Janice
Graves, Theresa
Cady, Blake
Ulin, Kenneth
Ruthazer, Robin
DiPetrillo, Thomas A.
Publication Title: 
Journal of the American Academy of Nurse Practitioners

PURPOSE: To describe herpes zoster ophthalmicus in relation to the anatomy, pathophysiology, course, diagnostic considerations, and management for the primary care provider. DATA SOURCES: Actual case study supplemented with an extensive review of current scientific and psychosocial literature. CONCLUSIONS: Herpes zoster ophthalmicus (HZO) is an extension of a herpes zoster (HZ) infection involving the fifth cranial (trigeminal) nerve, which results from the reactivation of a latent varicella virus among individuals who had contracted a varicella infection sometime within their lifespan.

Author(s): 
Temple, Jeffery J.
Publication Title: 
Cancer Research

The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells (MECs). One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence. However, the precise genetic changes that are responsible for this event in MECs is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc cooperating oncoprotein, can bypass senescence, extend the replicative life span, and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines.

Author(s): 
Dimri, Goberdhan P.
Martinez, Jose-Luis
Jacobs, Jacqueline J. L.
Keblusek, Petra
Itahana, Koji
Van Lohuizen, Maarten
Campisi, Judith
Wazer, David E.
Band, Vimla

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