keyword
MENU ▼
Read by QxMD icon Read
search

senolytics

keyword
https://www.readbyqxmd.com/read/29106993/the-role-of-cellular-senescence-in-aging-through-the-prism-of-koch-like-criteria
#1
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
#2
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...
October 18, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28957964/targeting-aging-for-disease-modification-in-osteoarthritis
#3
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...
September 27, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28871086/identification-of-hsp90-inhibitors-as-a-novel-class-of-senolytics
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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 p16(Ink4a)-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
https://www.readbyqxmd.com/read/28507307/a-novel-indication-for-panobinostat-as-a-senolytic-drug-in-nsclc-and-hnscc
#13
Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M McDaid
Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479002/inhibition-of-bcl-2-xl-with-abt-263-selectively-kills-senescent-type-ii-pneumocytes-and-reverses-persistent-pulmonary-fibrosis-induced-by-ionizing-radiation-in-mice
#14
Jin Pan, Deguan Li, Yanfeng Xu, Junling Zhang, Yueying Wang, Mengyi Chen, Shuai Lin, Lan Huang, Eun Joo Chung, Deborah E Citrin, Yingying Wang, Martin Hauer-Jensen, Daohong Zhou, Aimin Meng
PURPOSE: Ionizing radiation (IR)-induced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiation therapy. The goal of this study was to determine whether clearance of senescent cells with ABT-263, a senolytic drug that can selectively kill senescent cells, can reverse PF. METHODS AND MATERIALS: C57BL/6J mice were exposed to a single dose of 17 Gy on the right side of the thorax. Sixteen weeks after IR, they were treated with 2 cycles of vehicle or ABT-263 (50 mg/kg per day for 5 days per cycle) by gavage...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28455874/quantitative-identification-of-senescent-cells-in-aging-and-disease
#15
Anat Biran, Lior Zada, Paula Abou Karam, Ezra Vadai, Lior Roitman, Yossi Ovadya, Ziv Porat, Valery Krizhanovsky
Senescent cells are present in premalignant lesions and sites of tissue damage and accumulate in tissues with age. In vivo identification, quantification and characterization of senescent cells are challenging tasks that limit our understanding of the role of senescent cells in diseases and aging. Here, we present a new way to precisely quantify and identify senescent cells in tissues on a single-cell basis. The method combines a senescence-associated beta-galactosidase assay with staining of molecular markers for cellular senescence and of cellular identity...
August 2017: Aging Cell
https://www.readbyqxmd.com/read/28436958/local-clearance-of-senescent-cells-attenuates-the-development-of-post-traumatic-osteoarthritis-and-creates-a-pro-regenerative-environment
#16
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28425952/antioxidant-and-anti-senescence-effect-of-metformin-on-mouse-olfactory-ensheathing-cells-moecs-may-be-associated-with-increased-brain-derived-neurotrophic-factor-levels-an-ex-vivo-study
#17
Agnieszka Śmieszek, Zuzanna Stręk, Katarzyna Kornicka, Jakub Grzesiak, Christine Weiss, Krzysztof Marycz
Metformin, the popular anti-diabetic drug was shown to exert multiple biological effects. The most recent metformin gained attention as an agent that mobilizes endogenous progenitor cells and enhances regenerative potential of organisms, for example by promoting neurogenesis. In the present study, we examined the role of metformin on mouse olfactory ensheathing cells (mOECs) derived from animals receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The mOECs expanded ex vivo were characterized in terms of their cellular phenotype, morphology, proliferative activity, viability and accumulation of oxidative stress factors...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416161/cellular-senescence-a-translational-perspective
#18
REVIEW
James L Kirkland, Tamara Tchkonia
Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28408343/the-impact-of-cellular-senescence-in-skin-ageing-a-notion-of-mosaic-and-therapeutic-strategies
#19
REVIEW
Marie Toutfaire, Emilie Bauwens, Florence Debacq-Chainiaux
Cellular senescence is now recognized as one of the nine hallmarks of ageing. Recent data show the involvement of senescent cells in tissue ageing and some age-related diseases. Skin represents an ideal model for the study of ageing. Indeed, skin ageing varies between individuals depending on their chronological age but also on their exposure to various exogenous factors (mainly ultraviolet rays). If senescence traits can be detected with ageing in the skin, the senescent phenotype varies among the various skin cell types...
October 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28401730/dna-damage-and-senescence-in-osteoprogenitors-expressing-osx1-may-cause-their-decrease-with-age
#20
Ha-Neui Kim, Jianhui Chang, Lijian Shao, Li Han, Srividhya Iyer, Stavros C Manolagas, Charles A O'Brien, Robert L Jilka, Daohong Zhou, Maria Almeida
Age-related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age-dependent changes in mesenchymal osteoblast progenitors. However, there are no specific markers for these progenitors, and conclusions rely on results from in vitro cultures of mixed cell populations. Moreover, the culprits of such changes remain unknown...
August 2017: Aging Cell
keyword
keyword
119481
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"