title: Interventions to Slow Aging in Humans: Are We Ready?
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.
authors.affiliation: Davis School of Gerontology and Department of Biological Sciences, Longevity Institute, University of Southern California, Los Angeles, CA, 90089, USA.|IFOM, FIRC Institute of Molecular Oncology, Via Adamello 16, 20139, Milano, Italy.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph Stelzmann Strasse 9b, 50931, Koeln, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.affiliation: Department of Internal Medicine, Southern Illinois University-School of Medicine, Springfield, IL, 62794, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.affiliation: Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58203, USA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Brown-Borg
authors.affiliation: Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
authors.affiliation: Experimental Gerontology Section, TGB, NIA, NIH, 251 Bayview Blvd. Suite 100/Room 9C218, Baltimore, MD, 21224, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.affiliation: DIMES-Department of Specialty, Diagnostic and Experimental Medicine, Via S. Giacomo, 12, I-40126, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, The Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Gems
authors.affiliation: Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70809, USA.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.affiliation: Institute for Behavioral Genetics, University of Colorado at Boulder, Box 447, Boulder, CO, 80309, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Johnson
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, University of California, 600 16th Street, Room S312D, San Francisco, CA, 94158-2517, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, Campus Box 8031, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.affiliation: Department of Biomedical Sciences, Edison Biotechnology Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.affiliation: Institut für Alternsforschung, Universität Innsbruck, Rennweg 10, A-6020, Innsbruck, Austria.
authors.forename: Guenter
authors.initials: G
authors.lastname: Lepperdinger
authors.affiliation: Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstr. 50, Graz, 8010, Austria.|BioTechMed Graz, Humboldtstr. 50, Graz, 8010, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie mediche, Universita' di Palermo, Via Divisi 83, 90133, Palermo, Italy.
authors.forename: Mario G
authors.initials: MG
authors.lastname: Mirisola
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, 02115, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Mitchell
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, 87036, Rende, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann Institute, D-07745, Jena, Germany.
authors.forename: Karl L
authors.initials: KL
authors.lastname: Rudolph
authors.affiliation: Laboratories for Molecular Medicine, Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 70 Ship Street, Providence, RI, 02903, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Sedivy
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520, USA.|Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Shadel
authors.affiliation: Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.|Australia Glenn Labs for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spindler
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Yousin
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Genetics, Albert Einstein Medical Center, 1301 Morris Park Avenue, Bronx, NY, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.affiliation: Division of Medicine, University College London (UCL) - Institute for Liver and Digestive Health, Royal Free Hospital, London, UK.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001685:Biological Factors / Q000627:therapeutic use*; D031204:Caloric Restriction / Q000379:methods; D004032:Diet; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D055553:Prescription Drugs / Q000627:therapeutic use*; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D001685:Biological Factors; D055553:Prescription Drugs; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D037761:Sirtuins
keywords: aging; anti-aging; centenarians; dietary restriction; lifespan studies; longevity gene; longevity regulation