{"topic":"aging-longevity","sort":"top","limit":25,"offset":0,"count":25,"papers":[{"id":"doi:10.1016/j.cell.2022.11.001","kind":"review","title":"Hallmarks of aging: An expanding universe","authors":["Carlos López-Otı́n","Marı́a A. Blasco","Linda Partridge","Manuel Serrano","Guido Kroemer"],"author_count":5,"year":2023,"published":"2023-01-01","venue":"Cell","cited_by":6534,"doi":"10.1016/j.cell.2022.11.001","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2022.11.001","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2022.11.001","updated":null,"pmid":"36599349","pmcid":null,"openalex_id":"W4313531093","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Genetics, Aging, and Longevity in Model Organisms"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2013.05.039","kind":"review","title":"The Hallmarks of Aging","authors":["Carlos López-Otı́n","Marı́a A. Blasco","Linda Partridge","Manuel Serrano","Guido Kroemer"],"author_count":5,"year":2013,"published":"2013-06-01","venue":"Cell","cited_by":14978,"doi":"10.1016/j.cell.2013.05.039","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2013.05.039","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2013.05.039","updated":null,"pmid":"23746838","pmcid":null,"openalex_id":"W2126525177","pdf_url":"http://www.cell.com/article/S0092867413006454/pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Genetics, Aging, and Longevity in Model Organisms"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1186/gb-2013-14-10-r115","kind":"article","title":"DNA methylation age of human tissues and cell types","authors":["Horvath S"],"author_count":1,"year":2013,"published":"2013-01-01","venue":"Genome biology","cited_by":5694,"doi":"10.1186/gb-2013-14-10-r115","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/gb-2013-14-10-r115","archive_url":"https://space-kitty.com/papers/doi:10.1186/gb-2013-14-10-r115","updated":null,"pmid":"24138928","pmcid":"PMC4015143","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4015143/pdf","abstract":"Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"DNA methylation age of human tissues and cell types\" by Horvath S, https://doi.org/10.1186/gb-2013-14-10-r115, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.tcb.2018.02.001","kind":"review","title":"Hallmarks of Cellular Senescence","authors":["Alejandra Hernandez‐Segura","Jamil Nehme","Marco Demaria"],"author_count":3,"year":2018,"published":"2018-02-21","venue":"Trends in Cell Biology","cited_by":2597,"doi":"10.1016/j.tcb.2018.02.001","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.tcb.2018.02.001","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.tcb.2018.02.001","updated":null,"pmid":"29477613","pmcid":null,"openalex_id":"W2788548733","pdf_url":"http://www.cell.com/article/S0962892418300205/pdf","abstract":null,"abstract_license":null,"license":"other-oa","is_open_access":true,"peer_reviewed":null,"categories":["Telomeres, Telomerase, and Senescence"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41586-022-04569-5","kind":"article","title":"SARS-CoV-2 is associated with changes in brain structure in UK Biobank","authors":["Gwenaëlle Douaud","Soojin Lee","Fidel Alfaro‐Almagro","Christoph Arthofer","Chaoyue Wang","Paul McCarthy","Frederik Lange","Jesper Andersson","Ludovica Griffanti","Eugene Paul Duff","Saâd Jbabdi","Bernd Taschler","Peter Keating","Anderson M. Winkler","Rory Collins","Paul McMahan Matthews","Naomi E. Allen","Karla L. Miller","Thomas E. Nichols","Stephen M. Smith"],"author_count":20,"year":2022,"published":"2022-03-07","venue":"Nature","cited_by":1645,"doi":"10.1038/s41586-022-04569-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41586-022-04569-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41586-022-04569-5","updated":null,"pmid":"34189535","pmcid":null,"openalex_id":"W4220784902","pdf_url":"https://www.nature.com/articles/s41586-022-04569-5.pdf","abstract":". However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51-81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans-with 141 days on average separating their diagnosis and the second scan-as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"peer_reviewed":null,"categories":["Long-Term Effects of COVID-19"],"details":null,"provenance":"openalex","attribution":"Abstract of \"SARS-CoV-2 is associated with changes in brain structure in UK Biobank\" by Gwenaëlle Douaud, Soojin Lee, Fidel Alfaro‐Almagro et al., https://doi.org/10.1038/s41586-022-04569-5, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1111/acel.12344","kind":"article","title":"The Achilles' heel of senescent cells: from transcriptome to senolytic drugs","authors":["Zhu Y","Tchkonia T","Pirtskhalava T","Gower AC","Ding H","Giorgadze N","Palmer AK","Ikeno Y","Hubbard GB","Lenburg M","O'Hara SP","LaRusso NF","Miller JD","Roos CM","Verzosa GC","LeBrasseur NK","Wren JD","Farr JN","Khosla S","Stout MB","McGowan SJ","Fuhrmann-Stroissnigg H","Gurkar AU","Zhao J","Colangelo D"],"author_count":33,"year":2015,"published":"2015-04-22","venue":"Aging cell","cited_by":2112,"doi":"10.1111/acel.12344","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.12344","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.12344","updated":null,"pmid":"25754370","pmcid":"PMC4531078","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4531078/pdf","abstract":"The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1(-/Δ) mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1(-/∆) mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"The Achilles' heel of senescent cells: from transcriptome to senolytic drugs\" by Zhu Y, Tchkonia T, Pirtskhalava T et al., https://doi.org/10.1111/acel.12344, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s41467-022-32552-1","kind":"article","title":"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues","authors":["Saul D","Kosinsky RL","Atkinson EJ","Doolittle ML","Zhang X","LeBrasseur NK","Pignolo RJ","Robbins PD","Niedernhofer LJ","Ikeno Y","Jurk D","Passos JF","Hickson LJ","Xue A","Monroe DG","Tchkonia T","Kirkland JL","Farr JN","Khosla S"],"author_count":19,"year":2022,"published":"2022-08-16","venue":"Nature communications","cited_by":1042,"doi":"10.1038/s41467-022-32552-1","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-022-32552-1","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-022-32552-1","updated":null,"pmid":"35974106","pmcid":"PMC9381717","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9381717/pdf","abstract":"Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues\" by Saul D, Kosinsky RL, Atkinson EJ et al., https://doi.org/10.1038/s41467-022-32552-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/ncomms14532","kind":"article","title":"Cellular senescence mediates fibrotic pulmonary disease","authors":["Schafer MJ","White TA","Iijima K","Haak AJ","Ligresti G","Atkinson EJ","Oberg AL","Birch J","Salmonowicz H","Zhu Y","Mazula DL","Brooks RW","Fuhrmann-Stroissnigg H","Pirtskhalava T","Prakash YS","Tchkonia T","Robbins PD","Aubry MC","Passos JF","Kirkland JL","Tschumperlin DJ","Kita H","LeBrasseur NK"],"author_count":23,"year":2017,"published":"2017-02-23","venue":"Nature communications","cited_by":1435,"doi":"10.1038/ncomms14532","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/ncomms14532","archive_url":"https://space-kitty.com/papers/doi:10.1038/ncomms14532","updated":null,"pmid":"28230051","pmcid":"PMC5331226","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5331226/pdf","abstract":"Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Here we demonstrate elevated abundance of senescence biomarkers in IPF lung, with p16 expression increasing with disease severity. We show that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin (DQ), is fibrogenic. Leveraging the bleomycin-injury IPF model, we demonstrate that early-intervention suicide-gene-mediated senescent cell ablation improves pulmonary function and physical health, although lung fibrosis is visibly unaltered. DQ treatment replicates benefits of transgenic clearance. Thus, our findings establish that fibrotic lung disease is mediated, in part, by senescent cells, which can be targeted to improve health and function.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Cellular senescence mediates fibrotic pulmonary disease\" by Schafer MJ, White TA, Iijima K et al., https://doi.org/10.1038/ncomms14532, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1172/jci158447","kind":"review","title":"Mitochondrial dysfunction in cell senescence and aging","authors":["Satomi Miwa","Sonu Kashyap","Eduardo N. Chini","Thomas von Zglinicki"],"author_count":4,"year":2022,"published":"2022-06-30","venue":"Journal of Clinical Investigation","cited_by":1060,"doi":"10.1172/jci158447","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1172/jci158447","archive_url":"https://space-kitty.com/papers/doi:10.1172/jci158447","updated":null,"pmid":"35775483","pmcid":"PMC9246372","openalex_id":"W4283723802","pdf_url":"http://www.jci.org/articles/view/158447/files/pdf","abstract":"Mitochondrial dysfunction and cell senescence are hallmarks of aging and are closely interconnected. Mitochondrial dysfunction, operationally defined as a decreased respiratory capacity per mitochondrion together with a decreased mitochondrial membrane potential, typically accompanied by increased production of oxygen free radicals, is a cause and a consequence of cellular senescence and figures prominently in multiple feedback loops that induce and maintain the senescent phenotype. Here, we summarize pathways that cause mitochondrial dysfunction in senescence and aging and discuss the major consequences of mitochondrial dysfunction and how these consequences contribute to senescence and aging. We also highlight the potential of senescence-associated mitochondrial dysfunction as an antiaging and antisenescence intervention target, proposing the combination of multiple interventions converging onto mitochondrial dysfunction as novel, potent senolytics.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"peer_reviewed":null,"categories":["Mitochondrial Function and Pathology"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Mitochondrial dysfunction in cell senescence and aging\" by Satomi Miwa, Sonu Kashyap, Eduardo N. Chini et al., https://doi.org/10.1172/jci158447, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.ebiom.2019.08.069","kind":"article","title":"Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease","authors":["Hickson LJ","Langhi Prata LGP","Bobart SA","Evans TK","Giorgadze N","Hashmi SK","Herrmann SM","Jensen MD","Jia Q","Jordan KL","Kellogg TA","Khosla S","Koerber DM","Lagnado AB","Lawson DK","LeBrasseur NK","Lerman LO","McDonald KM","McKenzie TJ","Passos JF","Pignolo RJ","Pirtskhalava T","Saadiq IM","Schaefer KK","Textor SC"],"author_count":33,"year":2019,"published":"2019-09-18","venue":"EBioMedicine","cited_by":1119,"doi":"10.1016/j.ebiom.2019.08.069","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.ebiom.2019.08.069","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.ebiom.2019.08.069","updated":null,"pmid":"31542391","pmcid":"PMC6796530","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6796530/pdf","abstract":"Background Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans. Methods In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ± 3·1 years old; 2 female; BMI:33·9 ± 2·3 kg/m 2 ; eGFR:27·0 ± 2·1 mL/min/1·73m 2 ). Adipose tissue, skin biopsies, and blood were collected before and 11 days after completing senolytic treatment. Senescent cell and macrophage/Langerhans cell markers and circulating SASP factors were assayed. Findings D + Q reduced adipose tissue senescent cell burden within 11 days, with decreases in p16 INK4A -and p21 CIP1 -expressing cells, cells with senescence-associated β-galactosidase activity, and adipocyte progenitors with limited replicative potential. Adipose tissue macrophages, which are attracted, anchored, and activated by senescent cells, and crown-like structures were decreased. Skin epidermal p16 INK4A+ and p21 CIP1+ cells were reduced, as were circulating SASP factors, including IL-1α, IL-6, and MMPs-9 and -12. Interpretation \"Hit-and-run\" treatment with senolytics, which in the case of D + Q have elimination half-lives <11 h, significantly decreases senescent cell burden in humans. FUND: NIH and Foundations. ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease\" by Hickson LJ, Langhi Prata LGP, Bobart SA et al., https://doi.org/10.1016/j.ebiom.2019.08.069, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s43587-021-00098-4","kind":"review","title":"Autophagy in healthy aging and disease","authors":["Yahyah Aman","Tomas Schmauck‐Medina","Malene Hansen","Richard I. Morimoto","Anna Katharina Simon","Ivana Bjedov","Konstantinos Palikaras","Anne Simonsen","Terje Johansen","Nektarios Tavernarakis","David Chaim Rubinsztein","Linda Partridge","Guido Kroemer","John P. Labbadia","Evandro Fei Fang"],"author_count":15,"year":2021,"published":"2021-08-12","venue":"Nature Aging","cited_by":1313,"doi":"10.1038/s43587-021-00098-4","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s43587-021-00098-4","archive_url":"https://space-kitty.com/papers/doi:10.1038/s43587-021-00098-4","updated":null,"pmid":"34901876","pmcid":null,"openalex_id":"W3190631166","pdf_url":"https://www.nature.com/articles/s43587-021-00098-4.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Autophagy in Disease and Therapy"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1007/s12603-021-1665-8","kind":"article","title":"International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines","authors":["Míkel Izquierdo","Reshma Aziz Merchant","John Edward Morley","Stefan D. Anker","Iván Aprahamian","Hidenori Arai","Mylène Aubertin‐Leheudre","Roberto Bernabei","Eduardo Lusa Cadore","Matteo Cesari","Liang‐Kung Chen","Philipe de Souto Barreto","Gustavo Duque","Luigi Ferrucci","Roger A. Fielding","Antônio García‐Hermoso","Luis Miguel Gutiérrez‐Robledo","Stephen D. R. Harridge","Ben Kirk","Stephen B. Kritchevsky","Francesco Landi","Norman R. Lazarus","Finbarr C. Martin","Emanuele Marzetti","Marco Pahor"],"author_count":36,"year":2021,"published":"2021-07-01","venue":"The journal of nutrition health & aging","cited_by":1245,"doi":"10.1007/s12603-021-1665-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1007/s12603-021-1665-8","archive_url":"https://space-kitty.com/papers/doi:10.1007/s12603-021-1665-8","updated":null,"pmid":"34409961","pmcid":null,"openalex_id":"W3191864380","pdf_url":"https://link.springer.com/content/pdf/10.1007/s12603-021-1665-8.pdf","abstract":"The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"peer_reviewed":null,"categories":["Physical Activity and Health"],"details":null,"provenance":"openalex","attribution":"Abstract of \"International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines\" by Míkel Izquierdo, Reshma Aziz Merchant, John Edward Morley et al., https://doi.org/10.1007/s12603-021-1665-8, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.ebiom.2018.12.052","kind":"article","title":"Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study","authors":["Justice JN","Nambiar AM","Tchkonia T","LeBrasseur NK","Pascual R","Hashmi SK","Prata L","Masternak MM","Kritchevsky SB","Musi N","Kirkland JL"],"author_count":11,"year":2019,"published":"2019-01-05","venue":"EBioMedicine","cited_by":1030,"doi":"10.1016/j.ebiom.2018.12.052","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.ebiom.2018.12.052","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.ebiom.2018.12.052","updated":null,"pmid":"30616998","pmcid":"PMC6412088","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6412088/pdf","abstract":"Background Cellular senescence is a key mechanism that drives age-related diseases, but has yet to be targeted therapeutically in humans. Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal cellular senescence-associated disease. Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice. Methods A two-center, open-label study of intermittent DQ (D:100 mg/day, Q:1250 mg/day, three-days/week over three-weeks) was conducted in participants with IPF (n = 14) to evaluate feasibility of implementing a senolytic intervention. The primary endpoints were retention rates and completion rates for planned clinical assessments. Secondary endpoints were safety and change in functional and reported health measures. Associations with the senescence-associated secretory phenotype (SASP) were explored. Findings Fourteen patients with stable IPF were recruited. The retention rate was 100% with no DQ discontinuation; planned clinical assessments were complete in 13/14 participants. One serious adverse event was reported. Non-serious events were primarily mild-moderate, with respiratory symptoms (n = 16 total events), skin irritation/bruising (n = 14), and gastrointestinal discomfort (n = 12) being most frequent. Physical function evaluated as 6-min walk distance, 4-m gait speed, and chair-stands time was significantly and clinically-meaningfully improved (p < .05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health were unchanged. DQ effects on circulat.ing SASP factors were inconclusive, but correlations were observed between change in function and change in SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers r ≥ 0.50). Interpretation Our first-in-humans open-label pilot supports study feasibility and provides initial evidence that senolytics may alleviate physical dysfunction in IPF, warranting evaluation of DQ in larger randomized controlled trials for senescence-related diseases. ClinicalTrials.gov identifier: NCT02874989 (posted 2016-2018).","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study\" by Justice JN, Nambiar AM, Tchkonia T et al., https://doi.org/10.1016/j.ebiom.2018.12.052, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.cell.2013.11.037","kind":"article","title":"Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging","authors":["Ana P. Gomes","Nathan L. Price","Alvin J. Y. Ling","Javid J. Moslehi","Magdalene K. Montgomery","Luis A. Rajman","James P. White","João Soeiro Teodoro","Christiane D. Wrann","Basil P. Hubbard","Evi M. Mercken","Carlos M. Palmeira","Rafael de Cabo","Anabela Pinto Rolo","Nigel A. Turner","Eric L. Bell","David A. Sinclair"],"author_count":17,"year":2013,"published":"2013-12-01","venue":"Cell","cited_by":1478,"doi":"10.1016/j.cell.2013.11.037","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2013.11.037","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2013.11.037","updated":null,"pmid":"24360282","pmcid":null,"openalex_id":"W2171748049","pdf_url":"http://www.cell.com/article/S0092867413015213/pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Sirtuins and Resveratrol in Medicine"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41581-022-00601-z","kind":"review","title":"Cellular senescence: the good, the bad and the unknown","authors":["Weijun Huang","LaTonya J. Hickson","Alfonso Eirin","James L. Kirkland","Lilach O. Lerman"],"author_count":5,"year":2022,"published":"2022-08-03","venue":"Nature Reviews Nephrology","cited_by":1147,"doi":"10.1038/s41581-022-00601-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41581-022-00601-z","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41581-022-00601-z","updated":null,"pmid":"35922662","pmcid":null,"openalex_id":"W4289545008","pdf_url":"https://www.nature.com/articles/s41581-022-00601-z.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Telomeres, Telomerase, and Senescence"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1111/acel.12445","kind":"article","title":"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors","authors":["Zhu Y","Tchkonia T","Fuhrmann-Stroissnigg H","Dai HM","Ling YY","Stout MB","Pirtskhalava T","Giorgadze N","Johnson KO","Giles CB","Wren JD","Niedernhofer LJ","Robbins PD","Kirkland JL"],"author_count":14,"year":2016,"published":"2016-03-18","venue":"Aging cell","cited_by":960,"doi":"10.1111/acel.12445","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.12445","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.12445","updated":null,"pmid":"26711051","pmcid":"PMC4854923","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4854923/pdf","abstract":"Clearing senescent cells extends healthspan in mice. Using a hypothesis-driven bioinformatics-based approach, we recently identified pro-survival pathways in human senescent cells that contribute to their resistance to apoptosis. This led to identification of dasatinib (D) and quercetin (Q) as senolytics, agents that target some of these pathways and induce apoptosis preferentially in senescent cells. Among other pro-survival regulators identified was Bcl-xl. Here, we tested whether the Bcl-2 family inhibitors, navitoclax (N) and TW-37 (T), are senolytic. Like D and Q, N is senolytic in some, but not all types of senescent cells: N reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs), but not human primary preadipocytes, consistent with our previous finding that Bcl-xl siRNA is senolytic in HUVECs, but not preadipocytes. In contrast, T had little senolytic activity. N targets Bcl-2, Bcl-xl, and Bcl-w, while T targets Bcl-2, Bcl-xl, and Mcl-1. The combination of Bcl-2, Bcl-xl, and Bcl-w siRNAs was senolytic in HUVECs and IMR90 cells, while combination of Bcl-2, Bcl-xl, and Mcl-1 siRNAs was not. Susceptibility to N correlated with patterns of Bcl-2 family member proteins in different types of human senescent cells, as has been found in predicting response of cancers to N. Thus, N is senolytic and acts in a potentially predictable cell type-restricted manner. The hypothesis-driven, bioinformatics-based approach we used to discover that dasatinib (D) and quercetin (Q) are senolytic can be extended to increase the repertoire of senolytic drugs, including additional cell type-specific senolytic agents.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors\" by Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H et al., https://doi.org/10.1111/acel.12445, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/ncomms15691","kind":"article","title":"Cellular senescence drives age-dependent hepatic steatosis","authors":["Ogrodnik M","Miwa S","Tchkonia T","Tiniakos D","Wilson CL","Lahat A","Day CP","Burt A","Palmer A","Anstee QM","Grellscheid SN","Hoeijmakers JHJ","Barnhoorn S","Mann DA","Bird TG","Vermeij WP","Kirkland JL","Passos JF","von Zglinicki T","Jurk D"],"author_count":20,"year":2017,"published":"2017-06-13","venue":"Nature communications","cited_by":920,"doi":"10.1038/ncomms15691","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/ncomms15691","archive_url":"https://space-kitty.com/papers/doi:10.1038/ncomms15691","updated":null,"pmid":"28608850","pmcid":"PMC5474745","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5474745/pdf","abstract":"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. Conversely, inducing hepatocyte senescence promotes fat accumulation in vitro and in vivo. Mechanistically, we show that mitochondria in senescent cells lose the ability to metabolize fatty acids efficiently. Our study demonstrates that cellular senescence drives hepatic steatosis and elimination of senescent cells may be a novel therapeutic strategy to reduce steatosis.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Cellular senescence drives age-dependent hepatic steatosis\" by Ogrodnik M, Miwa S, Tchkonia T et al., https://doi.org/10.1038/ncomms15691, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.cmet.2018.05.011","kind":"review","title":"Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States","authors":["Mark P. Mattson","Thiruma Valavan Arumugam"],"author_count":2,"year":2018,"published":"2018-06-01","venue":"Cell Metabolism","cited_by":1239,"doi":"10.1016/j.cmet.2018.05.011","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cmet.2018.05.011","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cmet.2018.05.011","updated":null,"pmid":"29874566","pmcid":null,"openalex_id":"W2806146174","pdf_url":"http://www.cell.com/article/S1550413118303188/pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Genetics, Aging, and Longevity in Model Organisms"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.18632/aging.101508","kind":"article","title":"Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies","authors":["Horvath S","Oshima J","Martin GM","Lu AT","Quach A","Cohen H","Felton S","Matsuyama M","Lowe D","Kabacik S","Wilson JG","Reiner AP","Maierhofer A","Flunkert J","Aviv A","Hou L","Baccarelli AA","Li Y","Stewart JD","Whitsel EA","Ferrucci L","Matsuyama S","Raj K"],"author_count":23,"year":2018,"published":"2018-07-01","venue":"Aging","cited_by":783,"doi":"10.18632/aging.101508","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.18632/aging.101508","archive_url":"https://space-kitty.com/papers/doi:10.18632/aging.101508","updated":null,"pmid":"30048243","pmcid":"PMC6075434","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6075434/pdf","abstract":"DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies\" by Horvath S, Oshima J, Martin GM et al., https://doi.org/10.18632/aging.101508, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.neuron.2016.01.028","kind":"article","title":"PET Imaging of Tau Deposition in the Aging Human Brain","authors":["Michael Schöll","Samuel Neal Lockhart","Daniel R. Schonhaut","James P. O’Neil","Mustafa Janabi","Rik Ossenkoppele","Suzanne L. Baker","Jacob W. Vogel","Jamie Faria","Henry Schwimmer","Gil Dan Rabinovici","William J. Jagust"],"author_count":12,"year":2016,"published":"2016-03-01","venue":"Neuron","cited_by":1213,"doi":"10.1016/j.neuron.2016.01.028","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.neuron.2016.01.028","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.neuron.2016.01.028","updated":null,"pmid":"26938442","pmcid":null,"openalex_id":"W2290598353","pdf_url":"http://www.cell.com/article/S0896627316000532/pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"peer_reviewed":null,"categories":["Dementia and Cognitive Impairment Research"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1111/acel.12349","kind":"review","title":"DNA methylation and healthy human aging","authors":["Jones MJ","Goodman SJ","Kobor MS"],"author_count":3,"year":2015,"published":"2015-04-25","venue":"Aging cell","cited_by":741,"doi":"10.1111/acel.12349","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.12349","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.12349","updated":null,"pmid":"25913071","pmcid":"PMC4693469","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4693469/pdf","abstract":"The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"DNA methylation and healthy human aging\" by Jones MJ, Goodman SJ, Kobor MS, https://doi.org/10.1111/acel.12349, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1186/s13059-016-1030-0","kind":"article","title":"An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease","authors":["Horvath S","Gurven M","Levine ME","Trumble BC","Kaplan H","Allayee H","Ritz BR","Chen B","Lu AT","Rickabaugh TM","Jamieson BD","Sun D","Li S","Chen W","Quintana-Murci L","Fagny M","Kobor MS","Tsao PS","Reiner AP","Edlefsen KL","Absher D","Assimes TL"],"author_count":22,"year":2016,"published":"2016-08-11","venue":"Genome biology","cited_by":631,"doi":"10.1186/s13059-016-1030-0","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s13059-016-1030-0","archive_url":"https://space-kitty.com/papers/doi:10.1186/s13059-016-1030-0","updated":null,"pmid":"27511193","pmcid":"PMC4980791","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4980791/pdf","abstract":"Background Epigenetic biomarkers of aging (the \"epigenetic clock\") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. Results We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Conclusions Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease\" by Horvath S, Gurven M, Levine ME et al., https://doi.org/10.1186/s13059-016-1030-0, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1111/acel.12458","kind":"article","title":"Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice","authors":["Roos CM","Zhang B","Palmer AK","Ogrodnik MB","Pirtskhalava T","Thalji NM","Hagler M","Jurk D","Smith LA","Casaclang-Verzosa G","Zhu Y","Schafer MJ","Tchkonia T","Kirkland JL","Miller JD"],"author_count":15,"year":2016,"published":"2016-08-05","venue":"Aging cell","cited_by":626,"doi":"10.1111/acel.12458","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.12458","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.12458","updated":null,"pmid":"26864908","pmcid":"PMC5013022","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5013022/pdf","abstract":"While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long-term senolytic treatment is unknown. To determine whether long-term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease. Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senescent cell markers (TAF(+) cells) in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function (isolated organ chamber baths) in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Genetic clearance of senescent cells in aged normocholesterolemic INK-ATTAC mice phenocopied changes elicited by D+Q. Senolytics tended to reduce aortic calcification (alizarin red) and osteogenic signaling (qRT-PCR, immunohistochemistry) in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis (picrosirius red) was not changed appreciably by chronic senolytic treatment. This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice\" by Roos CM, Zhang B, Palmer AK et al., https://doi.org/10.1111/acel.12458, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.18632/aging.101202","kind":"article","title":"New agents that target senescent cells: the flavone, fisetin, and the BCL-X L inhibitors, A1331852 and A1155463","authors":["Zhu Y","Doornebal EJ","Pirtskhalava T","Giorgadze N","Wentworth M","Fuhrmann-Stroissnigg H","Niedernhofer LJ","Robbins PD","Tchkonia T","Kirkland JL"],"author_count":10,"year":2017,"published":"2017-03-01","venue":"Aging","cited_by":620,"doi":"10.18632/aging.101202","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.18632/aging.101202","archive_url":"https://space-kitty.com/papers/doi:10.18632/aging.101202","updated":null,"pmid":"28273655","pmcid":"PMC5391241","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5391241/pdf","abstract":"Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models. Reported senolytics include dasatinib, quercetin, navitoclax (ABT263), and piperlongumine. Here we report that fisetin, a naturally-occurring flavone with low toxicity, and A1331852 and A1155463, selective BCL-X L inhibitors that may have less hematological toxicity than the less specific BCL-2 family inhibitor navitoclax, are senolytic. Fisetin selectively induces apoptosis in senescent but not proliferating human umbilical vein endothelial cells (HUVECs). It is not senolytic in senescent IMR90 cells, a human lung fibroblast strain, or primary human preadipocytes. A1331852 and A1155463 are senolytic in HUVECs and IMR90 cells, but not preadipocytes. These agents may be better candidates for eventual translation into clinical interventions than some existing senolytics, such as navitoclax, which is associated with hematological toxicity.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"New agents that target senescent cells: the flavone, fisetin, and the BCL-X L inhibitors, A1331852 and A1155463\" by Zhu Y, Doornebal EJ, Pirtskhalava T et al., https://doi.org/10.18632/aging.101202, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.bbr.2010.11.058","kind":"review","title":"The cholinergic system in aging and neuronal degeneration","authors":["Reinhard Schliebs","Thomas Arendt"],"author_count":2,"year":2010,"published":"2010-12-10","venue":"Behavioural Brain Research","cited_by":1043,"doi":"10.1016/j.bbr.2010.11.058","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.bbr.2010.11.058","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.bbr.2010.11.058","updated":null,"pmid":"21145918","pmcid":null,"openalex_id":"W2085435800","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"peer_reviewed":null,"categories":["Alzheimer's disease research and treatments"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."}],"next":"https://space-kitty.com/api/v1/topics/aging-longevity/papers?sort=top&limit=25&offset=25"}