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https://www.readbyqxmd.com/read/29618945/inducers-of-senescence-toxic-compounds-and-senolytics-the-multiple-faces-of-nrf2-activating-phytochemicals-in-cancer-adjuvant-therapy
#1
REVIEW
Marco Malavolta, Massimo Bracci, Lory Santarelli, Md Abu Sayeed, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza, Andrea Basso, Maurizio Cardelli, Mauro Provinciali
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29616249/anti-aging-potential-of-tree-nuts-with-a-focus-on-the-phytochemical-composition-molecular-mechanisms-and-thermal-stability-of-major-bioactive-compounds
#2
REVIEW
Marius Emil Rusu, Ana-Maria Gheldiu, Andrei Mocan, Laurian Vlase, Daniela-Saveta Popa
Tree nuts, complete functional foods, contain macro- and micronutrients of high biological value. These bioactive compounds have a synergistic effect in preventing and delaying many age-related pathologies (e.g. cardiovascular diseases, stroke, type 2 diabetes mellitus, certain types of cancer, and several neurodegenerative diseases). Tree nuts are low in carbohydrates, but they abound in healthy fatty acids, in optimal proportion for a good plasma lipid profile, and are a good source of proteins, rich in proteinogenic amino acids...
April 4, 2018: Food & Function
https://www.readbyqxmd.com/read/29615539/induction-regulation-and-roles-of-neural-adhesion-molecule-l1cam-in-cellular-senescence
#3
Blanka Mrazkova, Rastislav Dzijak, Terezie Imrichova, Lenka Kyjacova, Peter Barath, Petr Dzubak, Dusan Holub, Marian Hajduch, Zuzana Nahacka, Ladislav Andera, Petr Holicek, Pavla Vasicova, Olena Sapega, Jiri Bartek, Zdenek Hodny
Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new cell-surface proteins differentially expressed on human SC. Besides previously reported proteins enriched on SC, we identified 78 proteins enriched and 73 proteins underrepresented in replicatively senescent BJ fibroblasts, including L1CAM, whose expression is normally restricted to the neural system and kidneys...
March 28, 2018: Aging
https://www.readbyqxmd.com/read/29556500/vascular-senescence-in-cardiovascular-and-metabolic-diseases
#4
Goro Katsuumi, Ippei Shimizu, Yohko Yoshida, Tohru Minamino
In mammals, aging is associated with accumulation of senescent cells. Stresses such as telomere shortening and reactive oxygen species induce "cellular senescence", which is characterized by growth arrest and alteration of the gene expression profile. Chronological aging is associated with development of age-related diseases, including heart failure, diabetes, and atherosclerotic disease, and studies have shown that accumulation of senescent cells has a causative role in the pathology of these age-related disorders...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29527222/age-and-tissue-specific-expression-of-senescence-biomarkers-in-mice
#5
Adam D Hudgins, Cagdas Tazearslan, Archana Tare, Yizhou Zhu, Derek Huffman, Yousin Suh
Cellular senescence is a state of irreversible cellular growth arrest accompanied by distinct changes in gene expression and the acquisition of a complex proinflammatory secretory profile termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in aged tissues and contribute to age-related disease in mice. Increasing evidence that selective removal of senescent cells can ameliorate diseases of late life and extend lifespan in mice has given rise to the development of senolytics that target senescent cells as anti-aging therapeutics...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29427795/cellular-senescence-immunosurveillance-and-future-immunotherapy
#6
REVIEW
Dominick G A Burton, Alexandra Stolzing
In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases...
February 7, 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29315311/investigation-of-quercetin-and-hyperoside-as-senolytics-in-adult-human-endothelial-cells
#7
HyunTae V Hwang, Darlene Thuy Tran, Michelle Nicole Rebuffatti, Chin-Shang Li, Anne A Knowlton
Previously, quercetin has been reported to be a senolytic, a drug that selectively removes senescent cells, in HUVECs. However, we found neither quercetin nor Q3G was effective as a senolytic for adult human endothelial cells.
2018: PloS One
https://www.readbyqxmd.com/read/29260442/cellular-senescence-in-the-aging-and-diseased-kidney
#8
REVIEW
F A Valentijn, L L Falke, T Q Nguyen, Roel Goldschmeding
The program of cellular senescence is involved in both the G1 and G2 phase of the cell cycle, limiting G1/S and G2/M progression respectively, and resulting in prolonged cell cycle arrest. Cellular senescence is involved in normal wound healing. However, multiple organs display increased senescent cell numbers both during natural aging and after injury, suggesting that senescent cells can have beneficial as well as detrimental effects in organismal aging and disease. Also in the kidney, senescent cells accumulate in various compartments with advancing age and renal disease...
March 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29106993/the-role-of-cellular-senescence-in-aging-through-the-prism-of-koch-like-criteria
#9
REVIEW
Hagai Yanai, Vadim E Fraifeld
Since Hayflick's discovery of cellular senescence (CS), a great volume of knowledge in the field has been accumulated and intensively discussed. Here, we attempted to organize the evidence "for" and "against" the hypothesized causal role of CS in aging. For that purpose, we utilized robust Koch-like logical criteria, based on the assumption that some quantitative relationships between the accumulation of senescent cells and aging rate should exist. If so, it could be expected that (i) the "CS load" would be greater in the premature aging phenotype and lesser in longevity phenotype; (ii) CS would promote age-related diseases, and (iii) the interventions that modulate the levels of senescent cells should also modulate health/lifespan...
October 26, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29054535/adipose-tissue-inflammation-in-aging
#10
REVIEW
Theresa Mau, Raymond Yung
Adipose tissue has traditionally been viewed as an organ of interest within studies of obesity and diet-associated metabolic disorders. However, as studies reveal the role white adipose tissue plays as an energy storage, a lipid metabolism site, and an adipokine secretor, it has become recognized as an organ of importance for metabolic health in both the young obese and the old obese. Within the realms of aging research, the pursuit of senolytics has taken the field's spotlight, where the clearance of senescent cells has shown to attenuate aspects of age-related disorders...
May 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/28957964/targeting-aging-for-disease-modification-in-osteoarthritis
#11
John A Collins, Brian O Diekman, Richard F Loeser
PURPOSE OF REVIEW: Age is a key risk factor for the development of osteoarthritis and age-related changes within the joint might represent targets for therapy. The recent literature was reviewed to find studies that provide new insight into the role of aging in osteoarthritis, with a focus on the potential for disease modification. RECENT FINDINGS: Preclinical studies using isolated cells and animal models provide evidence that two hallmarks of aging (cellular senescence and mitochondrial dysfunction) contribute to the development of osteoarthritis...
January 2018: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28871086/identification-of-hsp90-inhibitors-as-a-novel-class-of-senolytics
#12
Heike Fuhrmann-Stroissnigg, Yuan Yuan Ling, Jing Zhao, Sara J McGowan, Yi Zhu, Robert W Brooks, Diego Grassi, Siobhan Q Gregg, Jennifer L Stripay, Akaitz Dorronsoro, Lana Corbo, Priscilla Tang, Christina Bukata, Nadja Ring, Mauro Giacca, Xuesen Li, Tamara Tchkonia, James L Kirkland, Laura J Niedernhofer, Paul D Robbins
Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28869295/the-clinical-potential-of-senolytic-drugs
#13
James L Kirkland, Tamara Tchkonia, Yi Zhu, Laura J Niedernhofer, Paul D Robbins
Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage...
October 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28825716/targeting-cellular-senescence-prevents-age-related-bone-loss-in-mice
#14
Joshua N Farr, Ming Xu, Megan M Weivoda, David G Monroe, Daniel G Fraser, Jennifer L Onken, Brittany A Negley, Jad G Sfeir, Mikolaj B Ogrodnik, Christine M Hachfeld, Nathan K LeBrasseur, Matthew T Drake, Robert J Pignolo, Tamar Pirtskhalava, Tamara Tchkonia, Merry Jo Oursler, James L Kirkland, Sundeep Khosla
Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi)...
September 2017: Nature Medicine
https://www.readbyqxmd.com/read/28775044/senolytic-drugs-target%C3%A2-alveolar-epithelial-cell-function-and-attenuate-experimental-lung-fibrosis-ex-vivo
#15
Mareike Lehmann, Martina Korfei, Kathrin Mutze, Stephan Klee, Wioletta Skronska-Wasek, Hani N Alsafadi, Chiharu Ota, Rita Costa, Herbert B Schiller, Michael Lindner, Darcy E Wagner, Andreas Günther, Melanie Königshoff
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28728596/implementation-of-longevity-promoting-supplements-and-medications-in-public-health-practice-achievements-challenges-and-future-perspectives
#16
REVIEW
Alexander Vaiserman, Oleh Lushchak
BACKGROUND: Most modern societies undergo rapid population aging. The rise in life expectancy, nevertheless, is not accompanied, to date, by the same increment of healthspan. Efforts to increase healthspan by means of supplements and pharmaceuticals targeting aging-related pathologies are presently in spotlight of a new branch in geriatric medicine, geroscience, postulating that aging could be manipulated in such a way that will in parallel allow delay the onset of all age-associated chronic disorders...
July 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28695747/novel-strategies-for-anti-aging-drug-discovery
#17
REVIEW
Komal Saraswat, Syed Ibrahim Rizvi
Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of 'causes' which act either alone or in combination to create the condition which can be defined as 'aging'...
September 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28688962/stress-cell-senescence-and-organismal-ageing
#18
REVIEW
João Pedro de Magalhães, João F Passos
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing...
July 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28665427/effects-of-bioactive-compounds-on-senescence-and-components-of-senescence-associated-secretory-phenotypes-in-vitro
#19
REVIEW
Janubová Mária, Žitňanová Ingrid
Senescence is a permanent cell cycle arrest that is accompanied by changes in cell morphology and physiology occurring in vitro and in vivo. Senescence evolved as a beneficial response to damage promoting wound healing, limiting fibrosis, fighting against cancer and helping embryonic development. However, excessive accumulation of senescent cells is considered to play a substantial role in the development of aging-related diseases and other morphological and physiological changes associated with aging. Therefore, the aim of many researchers is to find out a way to eliminate senescent cells and improve the health condition of aging people...
July 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#20
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16Ink4a-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
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