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 ...
Cellular senescence is considered as a crucial mechanism of tumor suppression that helps to prevent the growth of cells at risk for neoplastic transformation. In normal cells, cellular senescence induces an irreversible cell cycle arrest in response to telomere dysfunction, oncoge ...
RNA interference (RNAi) is a powerful research tool that can be used to turn off—or silence—the expression of a specific gene. In recent years, RNAi screening on a genome-wide scale has provided the opportunity to identify factors and pathways involved in complex biological processes in a syste ...
Aging is a complex process, which involves changes in different cellular functions that all can be integrated on the metabolite level. This means that different gene regulation pathways that affect aging might lead to similar changes in metabolism and result in a metabolic signature of sene ...
Nutrient availability and nutrient-dependent biochemical signals represent major determinants of cellular senescence and organismal aging. The present chapter describes simple procedures to reliably evaluate the response of cultured cell to nutrients through the long ...
Sirtuins are a family of proteins with NAD+-dependent deacetylase or mono-ADP-ribosyltransferase activity. SIRT1, the mammalian ortholog most closely related to Sir2 (the first gene of this family discovered in yeast), exhibits anti-senescence activity in a wide range of mammalian ...