Protein Kinases

Publication Title: 
Experimental Cell Research

Cellular senescence is a state of irreversible cell cycle arrest in which normal cells at the end of their lifespan fail to enter into DNA synthesis upon serum or growth factor stimulation. We examined whether proteins required for G1/S cell cycle progression were irreversibly down-regulated in senescent human fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells.

Author(s): 
Afshari, C. A.
Vojta, P. J.
Annab, L. A.
Futreal, P. A.
Willard, T. B.
Barrett, J. C.
Publication Title: 
Human Molecular Genetics

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal models such as Caenorhabditis elegans and Drosophila melanogaster.

Author(s): 
MariÒo, Guillermo
Ugalde, Alejandro P.
Salvador-Montoliu, Natalia
Varela, Ignacio
QuirÛs, Pedro M.
CadiÒanos, Juan
van der Pluijm, Ingrid
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
Biochimica Et Biophysica Acta

Studies in a variety of model organisms indicate that nutrient signaling is tightly coupled to longevity. In nutrient replete conditions, organisms develop, grow, and age quickly. When nutrients become sparse as with dietary restriction, growth and development decline, stress response pathways become induced and organisms live longer. Considerable effort has been devoted to understanding the molecular events mediating lifespan extension by dietary restriction.

Author(s): 
Stanfel, Monique N.
Shamieh, Lara S.
Kaeberlein, Matt
Kennedy, Brian K.
Publication Title: 
The EMBO journal

Senescence is an irreversible cell-cycle arrest that is elicited by a wide range of factors, including replicative exhaustion. Emerging evidences suggest that cellular senescence contributes to ageing and acts as a tumour suppressor mechanism. To identify novel genes regulating senescence, we performed a loss-of-function screen on normal human diploid fibroblasts. We show that downregulation of the AMPK-related protein kinase 5 (ARK5 or NUAK1) results in extension of the cellular replicative lifespan.

Author(s): 
Humbert, Nicolas
Navaratnam, Naveenan
Augert, Arnaud
Da Costa, Marco
Martien, SÈbastien
Wang, Jing
Martinez, Dolores
Abbadie, Corinne
Carling, David
de Launoit, Yvan
Gil, Jesus
Bernard, David
Publication Title: 
Age (Dordrecht, Netherlands)

Chronological lifespan (CLS) is defined as the duration of quiescence in which normal cells retain the capacity to reenter the proliferative cycle. This study investigates whether hydroxytyrosol (HT), a naturally occurring polyphenol found in olives, extends CLS in normal human fibroblasts (NHFs). Quiescent NHFs cultured for a long duration (30-60†days) lose their capacity to repopulate. Approximately 60% of these cells exit the cell cycle permanently; a significant increase in the doubling time of the cell population was observed.

Author(s): 
Sarsour, Ehab H.
Kumar, Maneesh G.
Kalen, Amanda L.
Goswami, Monali
Buettner, Garry R.
Goswami, Prabhat C.
Publication Title: 
MÈdecine Sciences: M/S

During the last decade, studies aimed at investigating genes and molecular pathways involved in aging have been very fruitful and led to the identification of several mechanisms responsible for aging. Overall, those results put forward the capacity of cells and organisms to sense and respond to stress, as a critical factor for a healthy and long life. Those molecular pathways are tightly linked with the overall metabolism of an organism.

Author(s): 
Terret, Catherine
Solari, Florence
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or accelerated by a decline or loss of responsiveness to activation of the energy-sensing protein AMPK, a critical gerosuppressor of mTOR.

Author(s): 
Menendez, Javier A.
Joven, Jorge
AragonËs, Gerard
BarrajÛn-Catal·n, Enrique
Beltr·n-DebÛn, Ra˙l
Borr·s-Linares, Isabel
Camps, Jordi
Corominas-Faja, Bruna
CufÌ, SÌlvia
Fern·ndez-Arroyo, Salvador
Garcia-Heredia, Anabel
Hern·ndez-Aguilera, Anna
Herranz-LÛpez, MarÌa
JimÈnez-S·nchez, Cecilia
LÛpez-Bonet, Eugeni
Lozano-S·nchez, Jes˙s
Luciano-Mateo, Fedra
Martin-Castillo, BegoÒa
Martin-Paredero, Vicente
PÈrez-S·nchez, Almudena
Oliveras-Ferraros, Cristina
Riera-Borrull, Marta
RodrÌguez-Gallego, Esther
Quirantes-PinÈ, Rosa
Rull, Anna
Tom·s-Menor, Laura
Vazquez-Martin, Alejandro
Alonso-Villaverde, Carlos
Micol, Vicente
Segura-Carretero, Antonio
Publication Title: 
The Journal of Cell Biology

Werner and Bloom syndromes are human diseases characterized by premature age-related defects including elevated cancer incidence. Using a novel Saccharomyces cerevisiae model system for aging and cancer, we show that cells lacking the RecQ helicase SGS1 (WRN and BLM homologue) undergo premature age-related changes, including reduced life span under stress and calorie restriction (CR), G1 arrest defects, dedifferentiation, elevated recombination errors, and age-dependent increase in DNA mutations.

Author(s): 
Madia, Federica
Gattazzo, Cristina
Wei, Min
Fabrizio, Paola
Burhans, William C.
Weinberger, Martin
Galbani, Abdoulaye
Smith, Jesse R.
Nguyen, Christopher
Huey, Selina
Comai, Lucio
Longo, Valter D.
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: 
PloS One

Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries.

Author(s): 
Spindler, Stephen R.
Li, Rui
Dhahbi, Joseph M.
Yamakawa, Amy
Sauer, Frank

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