Janus Kinases (JAKs) are the key effector kinases that initiate intracellular signalling cascades in response to cytokines and growth factors. As such, a large number of cytoplasmic proteins interact with JAKs both as substrates and as components of regulatory machinery designed to en ...

The discovery that a range of myeloproliferative diseases and leukemias are associated with Janus Kinase (JAK) mutations has highlighted the importance of JAK/STAT signalling in disease and sparked a renewed interest in developing JAK inhibitors. In vitro kinase assays are the most di ...

Jak binding to cytokine receptors has been shown to be a complex and tight interaction. When studying loss-of-function or gain-of-function mutants of the Jaks or cytokine receptors it is often necessary to know if a certain mutant still associates correctly in the context of the signaling comp ...

Activation of Janus kinases (Jaks) occurs through autophosphorylation of key tyrosine residues located primarily within their catalytic domain. Phosphorylation of these tyrosine residues facilitates access of substrates to the active site and serves as an intrinsic indicat ...

Identifying molecules that serve as markers for cell aging is a goal that has been pursued by several groups. Senescence-associated β galactosidase (SA-βgal) staining is broadly used and very easily detected. β-gal is a lysosomal enzyme strongly correlated to the progression of cell senes ...

Most normal human cells have a finite replicative capacity and eventually undergo cellular senescence, whereby cells cease to proliferate. Cellular senescence is also induced by various stress signals, such as those generated by oncogenes, DNA damage, hyperproliferation, and an ox ...

Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Such an irreversible blockage is mainly mediated by the persis ...

One of the most prominent features of cellular senescence, a stress response that prevents the propagation of cells that have accumulated potentially oncogenic alterations, is a permanent loss of proliferative potential. Thus, at odds with quiescent cells, which resume proliferat ...

The characteristic features of senescent cells such as their “flattened” appearance, enlarged nuclei and low saturation density at the plateau phase of cell growth, can be conveniently measured by image-assisted cytometry such as provided by a laser scanning cytometer (LSC). The “flat ...

Cellular senescence is a tumor suppression mechanism that evolved to limit duplication in somatic cells. Senescence is imposed by natural replicative boundaries or stress-induced signals, such as oncogenic transformation. Neoplastic cells can be forced to undergo senescence t ...

p53, a guardian of the genome, exerts its tumor suppression activity by regulating a large number of downstream targets involved in cell cycle arrest, DNA repair, apoptosis, and cellular senescence. Although p53-mediated apoptosis is able to kill cancer cells, a role for cellular senescence ...

Zebrafish, a diurnal vertebrate characterized by gradual senescence, is an excellent model for studying age-dependent diseases, such as neurodegenerative diseases. Cerebral amyloid angiopathy (CAA) caused by amyloid β (Aβ) deposition around brain microvessels is a human neur ...

Senescence is associated with changes in gene expression, including the upregulation of stress response- and innate immune response-related genes. In addition, aging animals exhibit characteristic changes in movement behaviors including decreased gait speed and a deterior ...

Caenorhabditis elegans is becoming a multipurpose tool for genetic and chemical compound screening approaches aiming to identify and target the molecular mechanisms underlying senescent decline, aging, and associated pathologies. In this chapter, we describe specialized m ...

The nematode Caenorhabditis elegans provides a versatile and expedient platform for the genetic and molecular dissection of mechanisms underlying senescent decline and aging. Indeed, pioneering studies in this organism revealed the first genes and pathways directly influen ...

Saccharomyces cerevisiae is one of the most studied model organisms for the identification of genes and mechanisms that affect aging. The chronological lifespan (CLS) assay, which monitors the survival of a non-dividing population, is one of the two methods to study aging in yeast. To elimina ...

The senescence program is activated in response to diverse stress stimuli potentially compromising genetic stability and leads to an irreversible cell cycle arrest. The mTOR pathway plays a crucial role in the regulation of cell metabolism and cellular growth. The goal of this chapter is to p ...

Podospora anserina is an extensively studied model organism to unravel the mechanism of organismal aging. This filamentous fungus is short-lived and accessible to experimentation. Aging and lifespan are controlled by genetic and environmental traits and, in this model, have a strong ...

Bacteria, which are often considered as avid reproductive organisms under constant selective pressure to utilize available nutrients to proliferate, might seem an inappropriate model to study aging. However, environmental conditions are rarely supporting the exponential g ...

Cellular senescence, the irreversible loss of replicative capacity, is both a tumor suppressor mechanism and a contributor to the age-related loss of tissue function. However, the role of cellular senescence in vivo has been unclear, mostly because of the absence of cellular markers speci ...