TABLE OF CONTENTS


Editorial
Age-dependent patterns of microRNA RISC loading
Andrey Grigoriev and Nancy M. Bonini
pp 705-706
Priority Research Paper
Reversal of cognitive decline: A novel therapeutic program
Dale E. Bredesen
pp 707-717
Research Perspective
Translational Geroscience: Emphasizing function to achieve optimal longevity
Douglas R. Seals and Simon Melov
pp 718-730
Theory Article
Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins
Bruna Corominas-Faja, Elvira Santangelo, Elisabet Cuyàs, Vicente Micol, Jorge Joven, Xavier Ariza, Antonio Segura-Carretero, Jordi García, and Javier A. Menendez
pp 731-741
Research Papers
Rapamycin-induced metabolic defects are reversible in both lean and obese mice
Yuhong Liu, Vivian Diaz, Elizabeth Fernandez, Randy Strong, Lan Ye, Joseph A. Baur, Dudley W. Lamming, Arlan Richardson, and Adam B. Salmon
pp 742-754
Rapamycin treatment of Mandibuloacral Dysplasia cells rescues localization of chromatin-associated proteins and cell cycle dynamics
Vittoria Cenni, Cristina Capanni, Elisabetta Mattioli, Marta Columbaro, Manfred Wehnert, Michela Ortolani, Milena Fini, Giuseppe Novelli, Jessika Bertacchini, Nadir M. Maraldi, Sandra Marmiroli, Maria Rosaria D’Apice, Sabino Prencipe, Stefano Squarzoni, and Giovanna Lattanzi
pp 755-770
Age- and glycemia-related miR-126-3p levels in plasma and endothelial cells
Fabiola Olivieri, Massimiliano Bonafè, Liana Spazzafumo, Mirko Gobbi, Francesco Prattichizzo, Rina Recchioni, Fiorella Marcheselli, Lucia La Sala, Roberta Galeazzi, Maria Rita Rippo, Gianluca Fulgenzi, Sabrina Angelini, Raffaella Lazzarini, Anna Rita Bonfigli, Francesca Brugè, Luca Tiano, Stefano Genovese, Antonio Ceriello, Massimo Boemi, Claudio Franceschi, Antonio Domenico Procopio, and Roberto Testa
pp 771-787

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Impact Journals Director
Sergey DmitrievBoston, MA, USA

Sergey Dmitriev, a mathematician and programmer, President, CEO and Founder of a successful software company, JetBrains, based in St. Petersburg (Russia), Prague (Czech Republic) and Boston (USA). Journal's website is based on sophisticated programs developed by his company. His goal is creating a community around the journal, involving scientists and the public, and fostering aging research. Commentaries, interviews with the authors and members of the editorial board, discussions will be a part of the journal activity.

Editors-in-Chief
Mikhail V. Blagosklonny Roswell Park Cancer Institute, Buffalo, NY, USA

Mikhail V. Blagosklonny, M.D., Ph.D., Professor, Roswell Park Cancer Institute, Buffalo, NY, USA

Dr. Blagosklonny is author or co-author of over 150 articles in peer-reviewed journals. He is Associate Editor of Cancer Res, Cell Death Differ, Cancer Biol Ther, Autophagy, Int J Cancer, Am J Pathology, PLOS ONE and Editor-in-Chief of Cell Cycle. His research interests range from molecular and cellular biology to clinical investigations and include signal transduction, cell cycle, cellular senescence, anticancer therapeutics with emphasis on translation of basic science into new anticancer strategies Recently, he extended the study of signal transduction pathways from cancer to aging, revealing potential targets for slowing down aging and age-related diseases.

Judith Campisi Buck Institute for Age Research, Novato, CA, USA

Judith Campisi, Ph.D., Professor, Buck Institute for Age Research, Novato, CA, USA

Dr. Campisi received a Ph.D. from the State University of New York Stony Brook and postdoctoral training at the Dana Farber Cancer Institute and Harvard Medical School. She was Assistant and Associate Professor in Biochemistry at the Boston University Medical School, and joined the Lawrence Berkeley National Laboratory as Senior Scientist in 1991. In 2002, she moved part of her laboratory to the then newly-founded Buck Institute for Age Research. Campisi's work bridges the fields of cancer and aging, and includes contributions to understanding the evolution and mechanisms of tumor suppressor genes, the cellular damage responses of senescence and apoptosis, DNA repair mechanisms, telomere biology, and the role of genome maintenance in postponing aging and cancer. She has published >150 research papers, review articles and book chapters on her work, and has received several awards for her research. Her awards include a Cancer Scholar award from the American Cancer Society, Established Investigator award from the American Heart Association, two MERIT awards from the National Institute on Aging, a Senior Scholar Award from the Ellison Medical Foundation, the Irving Wright Award from the American Federation for Aging Research and Glenn Foundation Award from the Gerontological Society of America. Campisi serves or has served on numerous national and international scientific review panels, public and private scientific advisory panels, and the editorial boards of several scientific journals.

Web links:

http://www.lbl.gov/lifesciences

http://www.Buckinstitute.org

David A.Sinclair Harvard Medical School, Boston, MA, USA

David A.Sinclair, Professor of Pathology and Co-Director of the Glenn Laboratories for Aging Research at Harvard Medical School, Boston, MA, USA

Dr. Sinclair obtained a BSc (1st class honors) and a Ph.D. from the University of New South Wales in Sydney, Australia. From 1995-1999, he worked as a postdoctoral researcher with Lenny Guarente at M.I.T. Dr. Sinclair has received awards including The Australian Commonwealth Prize, a Helen Hay Whitney Postdoctoral Award, a Leukemia Society Fellowship, a Ludwig Scholarship, a Harvard-Armenise Fellowship, an American Association for Aging Research Fellowship, and a Fellowship and Senior Scholarship from the Ellison Medical Foundation.

Founding editorial board
Frederick Alt Harvard Medical School, Boston, MA, USA

Frederick W. Alt, Ph.D., member of the National Academy of Sciences, Professor, Harvard Medical School

Dr. Alt is also Investigator, Howard Hughes Medical Inst., Charles A. Janeway Professor of Pediatrics, HMS, Scientific Director, CBRI Institute for Biomedical Research.Fred Alt received a PhD from the Department of Biological Sciences at Stanford University. He is a Howard Hughes Medical Institute investigator, a member of the National Academy of Sciences and the American Academy of Sciences. He is the recipient of He is the recipient of the 2003 Excellence in Mentoring Award from the American Association of Immunologists and the 2004 Clowes Memorial Award from the American Association of Cancer Research. Editorial Boards: Mol. and Cell. Biology; Advances in Immunology; International Immunology; J. Exp. Med.; Current Opinion in Immunology; Immunity (founding Co-editor; 1993-present); Molecular Medicine (Contributing editor; 1997-present); Faculty of 1000 (co-head, Immunology). Honors and Awards: Fox Award, Stanford Univ. (1973); Hirschl Award (1983); Searle Scholar; (1983) Mallinckrodt Scholar; (1984); NIH Merit Award (1991); National Academy of Sciences (1994); American Academy of Microbiology (1994); American Academy of Arts and Sciences (1994); Associate (Foreign) Member, European Molecular Biology Organization (1999); Excellence in Mentoring Award,Association of Immunologists (2003); American Association of Cancer Research B.H.A. Clowes Award (2004); Rabi Shai Shacknai Memorial Prize in Immunology & Cancer Research (2005); Leukemia & Lymphoma Society de Villiers International Achievement Award (2005), Pasarow Foundation Prize in Cancer Research (2005); Irvington Institute Scientific Leadership in Immunology Award (2005); Establishment of Frederick W. Alt Award for New Discoveries in Immunology by the Irvington Institute (2006); National Cancer Institute Alfred Knudson Award in Cancer Genetics(2007).

Maria Blasco Spanish National Cancer Center, Madrid, Spain

Maria Blasco, PhD, Professor, Spanish National Cancer Research Center (CNIO), Madrid, Spain

Maria A. Blasco obtained her PhD in 1993 for her research on DNA polymerases at the Centro de Biología Molecular (Madrid) under the supervision of M. Salas. That same year, Blasco joined the Cold Spring Harbor Laboratory, New York, (USA), under the leadership of C. W. Greider. During this time, Blasco cloned one of the mammalian telomerase genes and generated the first telomerase knockout mouse. In 1997 she returned to Spain to start her own research group at the Centro Nacional de Biotecnología (Madrid), where she continued her work on the development of mouse models for the study of telomerase in cancer and ageing. She moved to the CNIO in 2003 as Director of the Molecular Oncology Program and Leader of the Telomeres and Telomerase Group. Blasco has received the Swiss Bridge Award for Research in Cancer, the Josef Steiner Cancer Research Award, the EMBO Gold Medal, the Rey Jaime I Basic Research Award and the Körber European Science Award. She is an elected EMBO Member since 2000 and a member of the Academia Europaea since 2006. She was appointed to the EMBO Council in 2008.

Judith Campisi Buck Institute for Age Research, Novato, CA, USA

Judith Campisi, Ph.D., Professor, Buck Institute for Age Research, Novato, CA, USA

Dr. Campisi received a Ph.D. from the State University of New York Stony Brook and postdoctoral training at the Dana Farber Cancer Institute and Harvard Medical School. She was Assistant and Associate Professor in Biochemistry at the Boston University Medical School, and joined the Lawrence Berkeley National Laboratory as Senior Scientist in 1991. In 2002, she moved part of her laboratory to the then newly-founded Buck Institute for Age Research. Campisi's work bridges the fields of cancer and aging, and includes contributions to understanding the evolution and mechanisms of tumor suppressor genes, the cellular damage responses of senescence and apoptosis, DNA repair mechanisms, telomere biology, and the role of genome maintenance in postponing aging and cancer. She has published >150 research papers, review articles and book chapters on her work, and has received several awards for her research. Her awards include a Cancer Scholar award from the American Cancer Society, Established Investigator award from the American Heart Association, two MERIT awards from the National Institute on Aging, a Senior Scholar Award from the Ellison Medical Foundation, the Irving Wright Award from the American Federation for Aging Research and Glenn Foundation Award from the Gerontological Society of America. Campisi serves or has served on numerous national and international scientific review panels, public and private scientific advisory panels, and the editorial boards of several scientific journals.

Web links:

http://www.lbl.gov/lifesciences

http://www.Buckinstitute.org

Lawrence A. Donehower Baylor College of Medicine, Houston, TX, USA

Lawrence A. Donehower, Ph.D., Professor, Department of Molecular Virology & Microbiology and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Ph.D., The George Washington University. Postdoctoral, University of California, San Francisco

Toren Finkel National Institutes of Health, Bethesda, MD, USA

Toren Finkel, M.D.,Ph.D., Principal Investigator, Chief of the Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Toren Finkel received his undergraduate degree in Physics and his MD and PhD degree from Harvard Medical School in 1986. Following a residency in Internal Medicine at the Massachusetts General Hospital he completed a fellowship in Cardiology at Johns Hopkins Medical School. In 1992, he accepted a position within the Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health in Bethesda, Maryland. In 2001 he became the Chief of the Cardiology Branch and in 2007 he became Chief of the newly formed Translational Medicine Branch within the NHLBI. His current research interests include the role of reactive oxygen species in aging and stem/progenitor cell dysfunction in age-related diseases.

Leonard Guarente MIT, Cambridge, MA,USA

Leonard Pershing Guarente, Ph.D., MIT Novartis Professor of Biology, MIT, Cambridge, MA, USA

Leonard Guarente formerly studied gene regulation in eukaryotes (1980-1995). In these early studies, his lab first purified the TATA-binding protein TBP and cloned the gene, discovered UASs, identified the first heteromeric transcription factor (HAP2/3/4/5), and provided the first evidence for coactivators. He then turned his studies to the mechanism of aging and its regulation using yeast and subsequently higher organisms. His lab began studying aging in 1991 and showed SIR2 is a critical longevity gene in yeast and C. elegans His lab discovered the novel biochemical activity of the SIR2 gene product ��� NAD-dependent protein deacetylase. This activity suggested that SIR2 might link diet to aging, addressing the longstanding question of how calorie restriction (CR) slows aging. His lab established a system to study CR in yeast and showed that CR extended the life span in yeast mother cells by activating SIR2. More recently, his lab has made several findings regarding the mammalian ortholog of SIR2, SIRT1. Importantly, it controls several physiological processes impacted by CR. First, Sirt1 renders cells stress resistant by inhibiting pro-apoptotic transcription factors p53 and forkhead. Second, Sirt1 also regulates many metabolic functions influenced by diet, for example the mobilization of fat from white adipocytes upon food limitation, and the increase in muscle maintenance during CR. These findings show that the life and health extension by CR are not passive events, but result from the activation of Sirt1, which then impacts on cellular and organismal processes to deliver the benefits. More recently, his and other labs have linked SIRT1 to protection against cardiovascular disease, diabetes, cancer, neurodegenerative disease and osteoporosis in mouse models. Dr. Guarente received his B. S. from MIT and his Ph. D. at Harvard, under the supervision of Jon Beckwith. He trained as a postdoctoral fellow at Harvard with Mark Ptashne and has been on the faculty of MIT since 1981, where he is the Novartis Professor of Biology. His book Ageless Quest (Cold Spring Harbor Press, 2003) describes the pathway of discovery of SIR2 as a key regulator of life span in response to diet.

Stephen L. Helfand Brown University, Providence, RI, USA

Stephen L. Helfand, MD, Professor in the Department of Molecular Biology, Cell Biology and Biochemistry in the Division of Biology and Medicine, Brown University

Dr. Helfand received his BS at Stanford University where he discovered the neuronal growth factor later renamed Ciliary Neuro Trophic Factor. Dr. Helfand obtained his MD degree from Albert Einstein College of Medicine, completed his Medical Internship at Montefiore Medical Center and his Neurology Residency at the Massachusetts General Hospital. He is Board Certified in Neurology. After Postdoctoral training at Stanford and at Yale he took a position at the University of Connecticut Health Center where from 1990 to 2005. In 2005 he moved to Brown University as Professor in the Department of Molecular Biology, Cell Biology and Biochemistry in the Division of Biology and Medicine. Dr. Helfand's laboratory focuses on understanding the molecular genetic mechanisms underlying aging and longevity using the model system, Drosophila melanogaster. Dr. Helfand is an Ellison Medical Foundation Senior Scholar, recipient of a Glenn Award for Research in Biological Mechanisms of Aging, RO1 awards and a MERIT award from the National Institute on Aging. His recent work on the molecular genetics of aging has appeared in journals including Science, Nature, Proceedings of the National Academy of Sciences, Cell Metabolism, Current Biology and Aging (Impact Aging.

Cynthia Kenyon University of California San Francisco, San Francisco, CA, USA

Cynthia Kenyon, Ph.D., member of the National Academy of Sciencs, American Cancer Society Professor and Director of the Hillblom Center for the Biology of Aging

Cynthia Kenyon received her PhD from MIT in 1981, where, in Graham Walker's laboratory, she was the first to look for genes on the basis of their expression profiles, discovering that DNA damaging agents activate a battery of DNA repair genes in E. coli. She then did postdoctoral studies with Nobel laureate Sydney Brenner at the MRC Laboratory of Molecular Biology in Cambridge, UK, studying the development of C. elegans. Since 1986 she has been at the University of California, San Francisco, where she was the Herbert Boyer Distinguished Professor of Biochemistry and Biophysics and is now an American Cancer Society Professor. In 1993, Kenyon and colleagues' discovery that a single-gene mutation could double the lifespan of C. elegans sparked an intensive study of the molecular biology of aging. These findings have now led to the discovery that an evolutionarily conserved hormone signaling system controls aging in other organisms as well, including mammals. Dr. Kenyon has received many honors and awards for her findings. She is a member of the US National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine and she is a past president of the Genetics Society of America. She is now the director of the Hillblom Center for the Biology of Aging at UCSF.

Arnold Levine The Institute for Advanced Study, Princeton, NJ, USA

Arnold J. Levine, Ph.D. member of the National Academy, Professor, The Simons Center for Systems Biology in the School of Natural Sciences at the Institute for Advanced Study, Princeton, NJ, USA.

Levine was on the faculty of the Biochemistry Department of Princeton University from1968 to 1979, when he became chair and professor in the Department of Microbiology at the State University of New York, Stony Brook, School of Medicine. Returning to Princeton University in 1984, he was named Harry C. Wiess Professor in the Life Sciences in the Department of Molecular Biology, a position he held until 1998. He chaired the Department between 1984 and 1996. He was President and Chief Executive Officer of the Rockefeller University in New York City from 1998 to 2002, as well as Heilbrunn Professor of Cancer Biology and laboratory head until joining the Institute in 2002. The recipient of many honors including: the Medal for Outstanding Contributions to Biomedical Research from Memorial Sloan-Kettering Cancer Center (2000); the Keio Medical Science Prize of the Keio University Medical Science Fund, Japan (2000); the Albany Medical Center Prize in Medicine and Biomedical Research (2001); and the Award for Basic Research from the Surgical Society of Oncologists (2003). Levine is a member of the National Academy of Sciences and of the Academy's Institute of Medicine; he is also the author or coauthor of over 300 scientific papers, as well as a book, Viruses (1993). He has served as board member or adviser to numerous scientific organizations and educational institutions, among them the N.J. Biotechnology Institute, the American Cyanamid Corporation, the SUNY Health Sciences Center in Brooklyn, Albert Einstein College of Medicine, the Weizmann Institute, the Huntsman Cancer Center of the University of Utah, and the Institute for Cancer Research in Lausanne, Switzerland.

Thomas Rando Stanford University School of Medicine, Stanford, CA, USA

Thomas A. Rando, MD, PhD, Associate Professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine; Chief Neurology Service VA Palo Alto Health Care System; Deputy Director, Stanford Center on Longevity (SCL)

Manuel Serrano Spanish National Cancer Research Center, Madrid, Spain

Manuel Serrano, PhD, Spanish National Cancer Research Center (CNIO), Madrid, Spain

Manuel Serrano obtained his PhD in 1991 at the University of Madrid for research on DNA replication under the supervision of Margarita Salas. From 1992 to 1996, Manuel worked as postdoctoral fellow in the laboratory of David Beach, at Cold Spring Harbor Laboratory (NY, USA). During this time, Manuel made his most important discovery with the cloning and characterization of p16, which defined a new class of cell cycle regulators and was soon recognized as a key tumor suppressor. In 1997, Manuel returned to Spain as an independent investigator, initially at the National Center of Biotechnology, and since 2003 at the Spanish National Cancer Research Center directed by Mariano Barbacid. The main contributions of Manuel during these years have been related to the concept of oncogene-induced senescence as a tumor suppression mechanism, the role of p19Arf as an oncogenic sensor, the generation of novel mouse models with increased cancer resistance, and the identification of senescent tumor cells within premalignant tumors. More recently, Manuel's laboratory has discovered a cis-regulatory element at the p16 and p19Arf locus, has dissected the role of DNA damage and oncogenic signaling in p53-mediated cancer protection, and has reported the anti-aging activity of the Arf/p53 module.

David A.Sinclair Harvard Medical School, Boston, MA, USA

David A.Sinclair, Professor of Pathology and Co-Director of the Glenn Laboratories for Aging Research at Harvard Medical School, Boston, MA, USA

Dr. Sinclair obtained a BSc (1st class honors) and a Ph.D. from the University of New South Wales in Sydney, Australia. From 1995-1999, he worked as a postdoctoral researcher with Lenny Guarente at M.I.T. Dr. Sinclair has received awards including The Australian Commonwealth Prize, a Helen Hay Whitney Postdoctoral Award, a Leukemia Society Fellowship, a Ludwig Scholarship, a Harvard-Armenise Fellowship, an American Association for Aging Research Fellowship, and a Fellowship and Senior Scholarship from the Ellison Medical Foundation.

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