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      An exposomic framework to uncover environmental drivers of aging

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          Abstract

          The exposome, the environmental complement of the genome, is an omics level characterization of an individual’s exposures. There is growing interest in uncovering the role of the environment in human health using an exposomic framework that provides a systematic and unbiased analysis of the non-genetic drivers of health and disease. Many environmental toxicants are associated with molecular hallmarks of aging. An exposomic framework has potential to advance understanding of these associations and how modifications to the environment can promote healthy aging in the population. However, few studies have used this framework to study biological aging. We provide an overview of approaches and challenges in using an exposomic framework to investigate environmental drivers of aging. While capturing exposures over a life course is a daunting and expensive task, the use of historical data can be a practical way to approach this research.

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          Most cited references135

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          A global reference for human genetic variation

          The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
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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 UK Biobank resource with deep phenotyping and genomic data

              The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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                Author and article information

                Journal
                Exposome
                Exposome
                exposome
                Exposome
                Oxford University Press
                2635-2265
                2022
                04 March 2022
                04 March 2022
                : 2
                : 1
                : osac002
                Affiliations
                [1 ] Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University , New York, NY 10032, USA
                [2 ] Department of Epidemiology and Robert N. Butler Columbia Aging Center, Mailman School of Public Health, Columbia University , New York, NY 10032, USA
                Author notes
                To whom correspondence should be addressed: Email: vk2316@ 123456cumc.columbia.edu
                Author information
                https://orcid.org/0000-0003-2244-6663
                https://orcid.org/0000-0001-5463-2212
                https://orcid.org/0000-0001-8984-1284
                Article
                osac002
                10.1093/exposome/osac002
                8917275
                35295547
                fad68112-f544-4850-ae71-2bc1ad13a6ee
                © The Author(s) 2022. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 24 January 2022
                : 27 September 2021
                : 19 January 2022
                : 12 March 2022
                Page count
                Pages: 11
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: P30 ES009089 and UL1TR001873
                Categories
                Review

                exposome,aging,hallmarks of aging,population-based studies of aging,measuring the exposome

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