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      Challenges in developing Geroscience trials

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          Abstract

          Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses (“Gerodiagnostics”). This article reports the main results of a Task Force of experts in Geroscience.

          Abstract

          Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This article reports a discussion of a research Task Force on the challenges posed by the clinical research in Geroscience so that future gerotherapeutic clinical trials can be conducted successfully.

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          Most cited references85

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Frailty in Older Adults: Evidence for a Phenotype

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              Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

              The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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                Author and article information

                Contributors
                rolland.y@chu-toulouse.fr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                19 August 2023
                19 August 2023
                2023
                : 14
                : 5038
                Affiliations
                [1 ]GRID grid.508721.9, Gérontopôle de Toulouse, IHU HealthAge, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, ; Toulouse, France
                [2 ]GRID grid.15781.3a, ISNI 0000 0001 0723 035X, CERPOP UMR 1295, University of Toulouse III, Inserm, UPS, ; Toulouse, France
                [3 ]Hevolution Foundation, Riyadh, Saudi Arabia
                [4 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, National Institute on Aging, , National Institutes of Health, ; Bethesda, MD USA
                [5 ]GRID grid.251993.5, ISNI 0000000121791997, Institute for Aging Research, , Albert Einstein College of Medicine, ; Bronx, NY USA
                [6 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Translational Gerontology Branch, National Institute on Aging, , National Institutes of Health, ; Baltimore, MD USA
                [7 ]Life Biosciences, Boston, MA USA
                [8 ]Longeveron Inc., Miami, FL USA
                [9 ]GRID grid.47840.3f, ISNI 0000 0001 2181 7878, Department of Nutritional Sciences and Toxicology, , University of California, ; Berkeley, CA USA
                [10 ]GRID grid.427612.4, ISNI 0000 0001 0395 8845, Noaber Foundation Professor of Aging Research, Mayo Clinic, Principal Investigator, NIH R33 Translational Geroscience Network, President, , American Federation for Aging Research, ; Rochester, NY USA
                [11 ]GRID grid.417944.b, ISNI 0000 0001 2188 9169, Centre de Recherche Pierre Fabre, ; Toulouse, France
                [12 ]Center on Aging and Mobility, Zurich, Switzerland
                [13 ]REGEnLIFE, Montpellier, France
                [14 ]Rejuveron, Zurich, Switzerland
                [15 ]GRID grid.462873.c, ISNI 0000 0004 0383 0990, CRCA—Centre de Recherches sur la Cognition Animale—UMR5169, ; Toulouse, France
                [16 ]Ridgeline Therapeutics, Houston, TX USA
                [17 ]Kinexum, Tolerion, Charlottesville, VA USA
                [18 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Université Paris Descartes, ; Paris, France
                [19 ]GRID grid.267309.9, ISNI 0000 0001 0629 5880, University of Texas Health Science, ; San Antonio, TX USA
                [20 ]Pentara Corporation, Salt Lake City, UT USA
                [21 ]Institut de Médecine Régénérative et Biothérapie, Montpellier, France
                [22 ]GRID grid.34477.33, ISNI 0000000122986657, University of Washington, ; Seattle, WA USA
                [23 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Wake Forest University School of Medicine, ; Winston-Salem, NC USA
                [24 ]GRID grid.427612.4, ISNI 0000 0001 0395 8845, American Federation for Aging Research, ; New York, NY USA
                [25 ]GRID grid.481970.3, Biophytis, ; Paris, France
                [26 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Imperial College London, ; London, UK
                [27 ]GRID grid.272799.0, ISNI 0000 0000 8687 5377, Buck Institute for Research on Aging, ; San Francisco, CA USA
                [28 ]GRID grid.475802.c, ISNI 0000 0004 0557 6068, Alliance for Aging Research, ; Washington, WA USA
                [29 ]GRID grid.417570.0, ISNI 0000 0004 0374 1269, Roche, ; Basel, Switzerland
                [30 ]Sagol Neuroscience and Longevity Network, Tel Aviv, Israel
                [31 ]Cambrian Biopharma, New York City, NY USA
                [32 ]GRID grid.157868.5, ISNI 0000 0000 9961 060X, CHU Montpellier, ; Montpellier, France
                [33 ]GRID grid.272799.0, ISNI 0000 0000 8687 5377, Buck Institute for Age Research, ; Novato, CA USA
                [34 ]GRID grid.17635.36, ISNI 0000000419368657, University of Minnesota Minneapolis, ; Minneapolis, MN USA
                [35 ]Insilico Medicine, Pak Shek Kok, Hong Kong
                Author information
                http://orcid.org/0009-0003-9486-9144
                http://orcid.org/0000-0002-6273-1613
                http://orcid.org/0000-0003-1676-4905
                Article
                39786
                10.1038/s41467-023-39786-7
                10439920
                37598227
                12449d2b-483f-48d4-afaa-3c50949822a3
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 February 2023
                : 29 June 2023
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2023

                Uncategorized
                target validation,cell death,drug development,randomized controlled trials
                Uncategorized
                target validation, cell death, drug development, randomized controlled trials

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