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      Interventions to Slow Aging in Humans: Are We Ready?

      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 , 34 , 35 , 36 , 37 , 38
      Aging Cell
      John Wiley & Sons, Ltd
      aging, anti-aging, centenarians, longevity regulation, dietary restriction, lifespan studies, longevity gene

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          Abstract

          The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

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          Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
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            The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

              Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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                Author and article information

                Journal
                Aging Cell
                Aging Cell
                acel
                Aging Cell
                John Wiley & Sons, Ltd (Chichester, UK )
                1474-9718
                1474-9726
                August 2015
                22 April 2015
                : 14
                : 4
                : 497-510
                Affiliations
                [1 ]Davis School of Gerontology and Department of Biological Sciences, Longevity Institute, University of Southern California Los Angeles, CA, 90089, USA
                [2 ]IFOM, FIRC Institute of Molecular Oncology Via Adamello 16, 20139, Milano, Italy
                [3 ]Max Planck Institute for Biology of Ageing Joseph Stelzmann Strasse 9b, 50931, Koeln, Germany
                [4 ]Department of Internal Medicine, Southern Illinois University-School of Medicine Springfield, IL, 62794, USA
                [5 ]Institute for Aging Research, Albert Einstein College of Medicine 1300 Morris Park Ave, Bronx, NY, 10461, USA
                [6 ]Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences Grand Forks, ND, 58203, USA
                [7 ]Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo Palermo, Italy
                [8 ]Department of Medicine, University of Texas Health Science Center San Antonio, TX, USA
                [9 ]Experimental Gerontology Section, TGB, NIA, NIH 251 Bayview Blvd. Suite 100/Room 9C218, Baltimore, MD, 21224, USA
                [10 ]DIMES-Department of Specialty, Diagnostic and Experimental Medicine Via S. Giacomo, 12, I-40126, Bologna, Italy
                [11 ]Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London The Darwin Building, Gower Street, London, WC1E 6BT, UK
                [12 ]Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System 6400 Perkins Road, Baton Rouge, LA, 70809, USA
                [13 ]Institute for Behavioral Genetics, University of Colorado at Boulder Box 447, Boulder, CO, 80309, USA
                [14 ]Buck Institute for Research on Aging Novato, CA, USA
                [15 ]Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, University of California 600 16th Street, Room S312D, San Francisco, CA, 94158-2517, USA
                [16 ]Center for Human Nutrition, Washington University School of Medicine Campus Box 8031, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
                [17 ]Department of Biomedical Sciences, Edison Biotechnology Institute, Heritage College of Osteopathic Medicine, Ohio University Athens, OH, 45701, USA
                [18 ]Institut für Alternsforschung, Universität Innsbruck Rennweg 10, A-6020, Innsbruck, Austria
                [19 ]Institute of Molecular Biosciences, NAWI Graz, University of Graz Humboldtstr. 50, Graz, 8010, Austria
                [20 ]BioTechMed Graz Humboldtstr. 50, Graz, 8010, Austria
                [21 ]Dipartimento di Biopatologia e Biotecnologie mediche, Universita’ di Palermo Via Divisi 83, 90133, Palermo, Italy
                [22 ]Department of Genetics and Complex Diseases, Harvard School of Public Health Boston, MA, 02115, USA
                [23 ]Department of Biology, Ecology and Earth Science, University of Calabria 87036, Rende, Italy
                [24 ]Leibniz Institute for Age Research, Fritz Lipmann Institute D-07745, Jena, Germany
                [25 ]Laboratories for Molecular Medicine, Department of Molecular Biology, Cell Biology and Biochemistry, Brown University 70 Ship Street, Providence, RI, 02903, USA
                [26 ]Department of Pathology, Yale University School of Medicine New Haven, CT, 06520, USA
                [27 ]Department of Genetics, Yale University School of Medicine New Haven, CT, 06520, USA
                [28 ]Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, UNSW Australia Sydney, NSW, Australia
                [29 ]Australia Glenn Labs for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School Boston, MA, Australia
                [30 ]Department of Biochemistry, University of California at Riverside Riverside, CA, USA
                [31 ]Department of Genetics, Albert Einstein College of Medicine Bronx, NY, USA
                [32 ]Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine Bronx, NY, USA
                [33 ]Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine Bronx, NY, USA
                [34 ]Department of Genetics, Albert Einstein Medical Center 1301 Morris Park Avenue, Bronx, NY, USA
                [35 ]Division of Medicine, University College London (UCL) – Institute for Liver and Digestive Health, Royal Free Hospital London, UK
                [36 ]Department of Medicine, Washington University School of Medicine St. Louis, MO, USA
                [37 ]Department of Clinical and Experimental Sciences, Brescia University Brescia, Italy
                [38 ]CEINGE Biotecnologie Avanzate Napoli, Italy
                Author notes
                Correspondence, Valter D Longo, Longevity Institute and School of Gerontology, 3715 Mcclintock ave, Los Angeles, CA 90089, USA. Tel.: +213-740-1757; e-mail: vlongo@ 123456usc.edu and, Luigi Fontana, Department of Medicine, Washington University in St.Louis, 660 S.Euclid Ave. – Campus Box 8113, St.Louis, MO 63110-1093, USA. Tel.: +1-314-747-1485; fax: +1-314-362-7657; e-mail: lfontana@ 123456dom.wustl.edu
                Article
                10.1111/acel.12338
                4531065
                25902704
                1a3ed4cf-a9c7-4162-bcdf-cff70832eb8d
                © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 February 2015
                Categories
                Reviews

                Cell biology
                aging,anti-aging,centenarians,longevity regulation,dietary restriction,lifespan studies,longevity gene

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