The Experts below are selected from a list of 28656 Experts worldwide ranked by ideXlab platform

Oliver Bischof - One of the best experts on this subject based on the ideXlab platform.

Ricardo Iván Martínez-zamudio - One of the best experts on this subject based on the ideXlab platform.

Alex Murray - One of the best experts on this subject based on the ideXlab platform.

  • A multidimensional systems biology analysis of Cellular Senescence in aging and disease
    Genome biology, 2020
    Co-Authors: Roberto A. Avelar, Javier Gómez Ortega, Robi Tacutu, Eleanor J. Tyler, Dominic Bennett, Paolo Binetti, Arie Budovsky, Kasit Chatsirisupachai, Emily Johnson, Alex Murray
    Abstract:

    Cellular Senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in Cellular Senescence, yet a comprehensive understanding of its pathways is still lacking. We develop CellAge (http://genomics.Senescence.info/cells), a manually curated database of 279 human genes driving Cellular Senescence, and perform various integrative analyses. Genes inducing Cellular Senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting Cellular Senescence overlap with pro-longevity and oncogenes. Furthermore, Cellular Senescence genes are strongly conserved in mammals but not in invertebrates. We also build Cellular Senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential Cellular Senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of Senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble Cellular Senescence. Overall, our work provides a benchmark resource for researchers to study Cellular Senescence, and our systems biology analyses reveal new insights and gene regulators of Cellular Senescence.

Fuyuki Ishikawa - One of the best experts on this subject based on the ideXlab platform.

  • Cellular Senescence and chromatin structure
    Chromosoma, 2007
    Co-Authors: Ryo Funayama, Fuyuki Ishikawa
    Abstract:

    Cellular Senescence is characterized by stable cell cycle arrest that is triggered by various forms of stress stimuli. Senescent cells show a series of morphological and physiological alterations including a flat and enlarged morphology, an increase in acidic β-galactosidase activity, chromatin condensation, and changes in gene expression pattern. These features are not observed in proliferating cells or quiescent cells in vitro. Using these Senescence markers, Cellular Senescence has been shown to occur in benign or premalignant lesions but not in malignant lesions and to act as a tumor-suppressing mechanism in vivo. The onset and maintenance of the senescent state are regulated by two tumor suppressor proteins, p53 and Rb, which mediate Senescence signals through p38 mitogen-activated protein kinase and cyclin-dependent kinase inhibitors. Alterations of chromatin structure are believed to contribute to the irreversible nature of the senescent state. Senescent cells form characteristic heterochromatin structure called Senescence-associated heterochromatic foci (SAHFs), which may repress the expression of proliferation-promoting genes, such as E2F target genes. Recent studies have provided molecular insights into the structure and the mechanism of SAHF formation. In this paper, we review the role of Cellular Senescence in tumor suppression in vivo and the molecular mechanism of stable growth arrest in senescent cells, focusing on the special form of heterochromatin, SAHFs.

  • Cellular Senescence as a stress response
    Cornea, 2006
    Co-Authors: Fuyuki Ishikawa
    Abstract:

    Purpose: This review discusses Cellular Senescence, the state in which normal cells do not respond to growth stimuli, and shows characteristic alterations in their cytologic and biochemical properties and their gene expression profiles. Methods and Results: Cellular Senescence is elicited by various stresses. It was recently shown that the stress-induced mitogen-activated protein kinase p38 has a pivotal role in inducing Cellular Senescence. This finding provided biochemical evidence to support the notion that Cellular Senescence is a kind of stress response. Conclusion: Stress responses are typically found in cells and organisms surviving unfavorable environmental conditions. It can be argued that Cellular Senescence is an adaptive process that maintains the cell's viability by reducing the energy consumed for reproduction (ie, cell division) and differentiation-related activities.

  • Cellular Senescence, an unpopular yet trustworthy tumor suppressor mechanism.
    Cancer Science, 2003
    Co-Authors: Fuyuki Ishikawa
    Abstract:

    The term “Cellular Senescence” refers to the state in which normal cells irreversibly stop dividing. Historically, this condition was first inferred from the finding that normal human fibroblasts cease dividing after a limited number of cell divisions. Since then, Cellular Senescence has been discussed as a potential cause of aging of organisms. However, recent studies have significantly expanded our view of Cellular Senescence in terms of both mechanistics and biological significance. Accordingly, Cellular Senescence is now considered to play an important adaptive role, namely, a tumor suppressor function. This review will focus on recent findings that have contributed to the elucidation of the adaptive role of Cellular Senescence.

Judith Campisi - One of the best experts on this subject based on the ideXlab platform.

  • Four faces of Cellular Senescence
    Journal of Cell Biology, 2011
    Co-Authors: Francis Rodier, Judith Campisi
    Abstract:

    Cellular Senescence is an important mechanism for preventing the proliferation of potential cancer cells. Recently, however, it has become apparent that this process entails more than a simple cessation of cell growth. In addition to suppressing tumorigenesis, Cellular Senescence might also promote tissue repair and fuel inflammation associated with aging and cancer progression. Thus, Cellular Senescence might participate in four complex biological processes (tumor suppression, tumor promotion, aging, and tissue repair), some of which have apparently opposing effects. The challenge now is to understand the Senescence response well enough to harness its benefits while suppressing its drawbacks.

  • Recent advances in Cellular Senescence, cancer and aging
    Biotechnology and Bioprocess Engineering, 2001
    Co-Authors: Chang-su Lim, Judith Campisi
    Abstract:

    How much do we know about the biology of aging from cell culture studies? Most normal somatic cells have a finite potential to divide due to a process termed Cellular or replicative Senescence. A growing body of evidence suggests that Senescence evolved to protect higher eukaryotes, particularly mammals, from developing cancer. We now know that telomere shortening, due to the biochemistry of DNA replication, induces replicative Senescence in human cells. However, in rodent cells, replicative Senescence occurs despite very long telomeres. Recent findings suggest that replicative Senescence is just the tip of the iceberg of a more general process termed Cellular Senescence. It appears that Cellular Senescence is a response to potentially oncogenic insults, including oxidative damage. In young organisms, growth arrest by cell Senescence suppresses tumor development, but later in life, due to the accumulation of senescent cells which secret factors that can disrupt tissues during aging, Cellular Senescence promotes tumorigenesis. Therefore, antagonistic pleiotropy may explain in part, if not in whole, the apparently paradoxical effects of Cellular Senescence, though this still remains an open question.

  • Regulation of Cellular Senescence by p53
    FEBS Journal, 2001
    Co-Authors: Koji Itahana, Goberdhan P. Dimri, Judith Campisi
    Abstract:

    Many normal cells respond to potentially oncogenic stimuliby undergoing Cellular Senescence, a state of irreversiblyarrested proliferation and altered differentiated function.Cellular Senescence very likely evolved to suppresstumorigenesis. In support of this idea, it is regulated byseveral tumor suppressor genes. At the heart of thisregulation is p53. p53 is essential for the Senescenceresponse to short telomeres, DNA damage, oncogenes andsupraphysiological mitogenic signals, and overexpressionof certain tumor suppressor genes. Despite the well-documented central role for p53 in the Senescenceresponse, many questions remain regarding how p53 sensesSenescence-inducing stimuli and how it elicits the senescentphenotype.Keywords: Cellular Senescence; cyclin-dependent kinaseinhibitors; DNA repair proteins; E2F1; p14/ ARF; p21; p53;PML; RAS; telomeres; tumor suppressors.p53 is an extraordinary protein whose activities lie at theheart of a remarkable number of basic Cellular processes.Here, we discuss the role of p53 in Cellular Senescence, afundamental Cellular response to a variety of damaging orpotentially oncogenic stimuli.Nearly 40 years ago, Hayflick and colleagues [1]described the finite proliferative lifespan, or replicativeSenescence, of normal human cells. Four decades ofsubsequent research have uncovered the primary mechan-ism by which replicative Senescence occurs (telomereshortening), as well as the realization that the Senescenceresponse is not limited to replicative exhaustion. Inaddition, it is now clear that the senescent phenotype isquite complex, entailing changes in cell function as well asarrested cell division. Finally, there are marked differencesamong species in the propensity of cells to spontaneouslyescape Senescence and acquire an indefinite or immortalreplicative lifespan. In this regard, rodent cells are muchmore prone to spontaneous immortalization than humancells (reviewed in [2–4]).Because a variety of stimuli, many of which arepotentially oncogenic, induce a senescent phenotype,Cellular Senescence, or the Senescence response, is verylikely a failsafe mechanism to prevent the proliferation ofcells that are at risk for tumorigenic transformation. In thisregard, Cellular Senescence is analogous to apoptosis,although it is decidedly distinct from apoptosis in manyrespects [5]. Apoptosis, of course, causes damaged orpotentially oncogenic cells to die, thereby eliminating themfrom tissues. Cellular Senescence, by contrast, arrests theproliferation of such cells, but does not eliminate them fromtissues. Despite these dissimilar Cellular outcomes, bothapoptosis and Cellular Senescence are important means forsuppressing the development of cancer in mammals, andboth processes are regulated at critical steps by p53.

  • Cellular Senescence, Aging and Cancer
    The Scientific World Journal, 2001
    Co-Authors: Judith Campisi
    Abstract:

    INTRODUCTION. Mammalian cells can respond to damage or stress by entering a state of irreversibly arrested growth and altered function termed Cellular Senescence. The Senescence response can be elicited by one or more critically short telomere (replicative Senescence), certain types of DNA damage or changes in chromatin structure, the expression of certain oncogenes, and supraphysiological mitogenic signals. Several lines of evidence suggest that Cellular Senescence evolved to suppress the development of cancer. Cellular Senescence has also been proposed to contribute to aging, although strong evidence for this idea has been lacking.