4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      ARDD 2020: from aging mechanisms to interventions

      review-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 10 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 28 , 42 , 7 , 43 , 1 , 37 , 44 , 45 , 46 , 1 , 47 , 48 , 49 , 50 , 31 , 51 , 52 , 53 , 54 , 55 , 56 , 10 , 5 , 57 , 43 , 1 , 58 , 1 ,
      Aging (Albany NY)
      Impact Journals
      aging, interventions, drug discovery, artificial intelligence

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7 th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1 st to 4 th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8 th ARDD meeting that is scheduled for the 31 st of August to 3 rd of September, 2021, at Columbia University, USA.

          Related collections

          Most cited references114

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          An epigenetic biomarker of aging for lifespan and healthspan

          Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            DNA methylation GrimAge strongly predicts lifespan and healthspan

            It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based estimators of plasma proteins including those of plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. The resulting predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogates and a DNAm-based estimator of smoking pack-years. Adjusting DNAm GrimAge for chronological age generated novel measure of epigenetic age acceleration, AgeAccelGrim. Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E-75), time-to-coronary heart disease (Cox P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E-17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P= 7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment. Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease

              Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.
                Bookmark

                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 December 2020
                30 December 2020
                : 12
                : 24
                : 24484-24503
                Affiliations
                [1 ]Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
                [2 ]Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
                [3 ]Amazentis SA, EPFL Innovation Park, Bâtiment C, Lausanne, Switzerland
                [4 ]Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
                [5 ]Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
                [6 ]Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
                [7 ]Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
                [8 ]Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, W12 0NN, UK
                [9 ]Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
                [10 ]Buck Institute for Research on Aging, Novato, CA 94945, USA
                [11 ]Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA
                [12 ]European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, The Netherlands
                [13 ]Institute of Translational Medicine, Department of Health Sciences and Technology, Swiss Federal Institute for Technology Zürich, Switzerland
                [14 ]Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway
                [15 ]School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK
                [16 ]Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
                [17 ]Calico Life Sciences, LLC, South San Francisco, CA 94080, USA
                [18 ]Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
                [19 ]HautAI OÜ, Tallinn, Estonia
                [20 ]Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
                [21 ]Regeneron Pharmaceuticals, Inc. Tarrytown, NY 10591, USA
                [22 ]Departments of Biology and Medicine, University of Rochester, Rochester, NY 14627, USA
                [23 ]SENS Research Foundation, Mountain View, CA 94041, USA
                [24 ]Human Longevity Inc., San Diego, CA 92121, USA
                [25 ]Department of Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [26 ]DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
                [27 ]Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
                [28 ]Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
                [29 ]Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
                [30 ]Gordian Biotechnology, San Francisco, CA 94107, USA
                [31 ]Blavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, MA 94107, USA
                [32 ]Molecular Endocrinology Unit, Department of Endocrinology, University Hospital of Odense and University of Southern Denmark, Odense, Denmark
                [33 ]Department of Molecular Cancer Research, Center for Molecular Medicine, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
                [34 ]Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University Singapore, Singapore
                [35 ]Centre for Healthy Ageing, National University Healthy System, Singapore
                [36 ]Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA
                [37 ]Department of Medicine, University of Wisconsin-Madison and William S. Middleton Memorial Veterans Hospital, Madison, WI 53792, USA
                [38 ]Sinovation Ventures and Sinovation AI Institute, Beijing, China
                [39 ]Department of Neuroscience, University of Copenhagen, Denmark
                [40 ]Deep Longevity Inc., Hong Kong Science and Technology Park, Hong Kong
                [41 ]Juvenescence Limited, Douglas, Isle of Man, UK
                [42 ]Institute of Biology of FRC Komi Science Center of Ural Division of RAS, Syktyvkar, Russia
                [43 ]Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
                [44 ]University of Pittsburgh, Pittsburgh, PA 15260, USA
                [45 ]Institute of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany
                [46 ]Department of Neurology and Neurological Sciences and Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305, USA
                [47 ]OneSkin Inc., San Francisco, CA 94107, USA
                [48 ]Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden
                [49 ]Department of Biomedical Sciences, University of Padova, Italy
                [50 ]Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Cologne, Germany
                [51 ]Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW, Australia
                [52 ]Departments of Obstetrics and Gynecology, Genetics and Development, Columbia University, New York, NY 10027, USA
                [53 ]Division of Cardiovascular Medicine, University of California, San Diego, CA 92093, USA
                [54 ]Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
                [55 ]Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
                [56 ]Max Planck Institute for Biology of Ageing, Cologne, Germany
                [57 ]Longevity Vision Fund, New York, NY 10022, USA
                [58 ]Insilico Medicine, Hong Kong Science and Technology Park, Hong Kong
                Author notes
                Correspondence to: Morten Scheibye-Knudsen; email: mscheibye@sund.ku.dk
                Article
                202454 202454
                10.18632/aging.202454
                7803558
                33378272
                272bb788-1dd3-4e8f-83dd-9b31e3e8ccc9
                Copyright: © 2020 Mkrtchyan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 November 2020
                : 12 December 2020
                Categories
                Meeting Report

                Cell biology
                aging,interventions,drug discovery,artificial intelligence
                Cell biology
                aging, interventions, drug discovery, artificial intelligence

                Comments

                Comment on this article