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      Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration

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          Abstract

          Despite significant overlaps in mission, the fields of environmental health sciences and aging biology are just beginning to intersect. It is increasingly clear that genetics alone does not predict an individual’s neurological aging and sensitivity to disease. Accordingly, aging neuroscience is a growing area of mutual interest within environmental health sciences. The impetus for this review came from a workshop hosted by the National Academies of Sciences, Engineering, and Medicine in June of 2020, which focused on integrating the science of aging and environmental health research. It is critical to bridge disciplines with multidisciplinary collaborations across toxicology, comparative biology, epidemiology to understand the impacts of environmental toxicant exposures and age-related outcomes. This scoping review aims to highlight overlaps and gaps in existing knowledge and identify essential research initiatives. It begins with an overview of aging biology and biomarkers, followed by examples of synergy with environmental health sciences. New areas for synergistic research and policy development are also discussed. Technological advances including next-generation sequencing and other-omics tools now offer new opportunities, including exposomic research, to integrate aging biomarkers into environmental health assessments and bridge disciplinary gaps. This is necessary to advance a more complete mechanistic understanding of how life-time exposures to toxicants and other physical and social stressors alter biological aging. New cumulative risk frameworks in environmental health sciences acknowledge that exposures and other external stressors can accumulate across the life course and the advancement of new biomarkers of exposure and response grounded in aging biology can support increased understanding of population vulnerability. Identifying the role of environmental stressors, broadly defined, on aging biology and neuroscience can similarly advance opportunities for intervention and translational research. Several areas of growing research interest include expanding exposomics and use of multi-omics, the microbiome as a mediator of environmental stressors, toxicant mixtures and neurobiology, and the role of structural and historical marginalization and racism in shaping persistent disparities in population aging and outcomes. Integrated foundational and translational aging biology research in environmental health sciences is needed to improve policy, reduce disparities, and enhance the quality of life for older individuals.

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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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            The NLRP3 inflammasome: molecular activation and regulation to therapeutics

            NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
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              Global trends in emerging infectious diseases

              The next new disease Emerging infectious diseases are a major threat to health: AIDS, SARS, drug-resistant bacteria and Ebola virus are among the more recent examples. By identifying emerging disease 'hotspots', the thinking goes, it should be possible to spot health risks at an early stage and prepare containment strategies. An analysis of over 300 examples of disease emerging between 1940 and 2004 suggests that these hotspots can be accurately mapped based on socio-economic, environmental and ecological factors. The data show that the surveillance effort, and much current research spending, is concentrated in developed economies, yet the risk maps point to developing countries as the more likely source of new diseases. Supplementary information The online version of this article (doi:10.1038/nature06536) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                21 February 2022
                2022
                : 14
                : 824921
                Affiliations
                [1] 1Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI, United States
                [2] 2Buck Institute for Research on Aging , Novato, CA, United States
                [3] 3United States Environmental Protection Agency, Office of Research and Development , Durham, NC, United States
                [4] 4Division of National Toxicology Program, National Institute of Environmental Health Sciences , Durham, NC, United States
                [5] 5Division of Intramural Research, Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health , Durham, NC, United States
                [6] 6Department of Health and Human Services, National Institute on Minority Health and Health Disparities, National Institutes of Health , Bethesda, MD, United States
                [7] 7Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Denver , Denver, CO, United States
                [8] 8Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , New York, NY, United States
                [9] 9Department of Biology and Biochemistry, University of Houston , Houston, TX, United States
                Author notes

                Edited by: Thomas C. Foster, University of Florida, United States

                Reviewed by: Paul G. Shiels, University of Glasgow, United Kingdom; Darryl Brice Hood, The Ohio State University, United States

                *Correspondence: Kristen M. C. Malecki, kmalecki@ 123456wisc.edu

                This article was submitted to Cellular and Molecular Mechanisms of Brain-aging, a section of the journal Frontiers in Aging Neuroscience

                Article
                10.3389/fnagi.2022.824921
                8901047
                35264945
                eb355e79-1a1e-4337-aae9-b9f4b3eb467b
                Copyright © 2022 Malecki, Andersen, Geller, Harry, Jackson, James, Miller and Ottinger.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 November 2021
                : 12 January 2022
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 245, Pages: 19, Words: 16846
                Funding
                Funded by: National Institutes of Health, doi 10.13039/100000002;
                Categories
                Neuroscience
                Review

                Neurosciences
                aging biology,gerotoxicology,toxicants,exposome,cumulative risk
                Neurosciences
                aging biology, gerotoxicology, toxicants, exposome, cumulative risk

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