91
views
0
recommends
+1 Recommend
0 collections
    0
    comments
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Epigenetics across the human lifespan

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Epigenetics has the potential to explain various biological phenomena that have heretofore defied complete explication. This review describes the various types of endogenous human developmental milestones such as birth, puberty, and menopause, as well as the diverse exogenous environmental factors that influence human health, in a chronological epigenetic context. We describe the entire course of human life from periconception to death and chronologically note all of the potential internal timepoints and external factors that influence the human epigenome. Ultimately, the environment presents these various factors to the individual that influence the epigenome, and the unique epigenetic and genetic profile of each individual also modulates the specific response to these factors. During the course of human life, we are exposed to an environment that abounds with a potent and dynamic milieu capable of triggering chemical changes that activate or silence genes. There is constant interaction between the external and internal environments that is required for normal development and health maintenance as well as for influencing disease load and resistance. For example, exposure to pharmaceutical and toxic chemicals, diet, stress, exercise, and other environmental factors are capable of eliciting positive or negative epigenetic modifications with lasting effects on development, metabolism and health. These can impact the body so profoundly as to permanently alter the epigenetic profile of an individual. We also present a comprehensive new hypothesis of how these diverse environmental factors cause both direct and indirect epigenetic changes and how this knowledge can ultimately be used to improve personalized medicine.

          Related collections

          Most cited references155

          • Record: found
          • Abstract: found
          • Article: not found

          Epigenetic programming by maternal behavior.

          Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            Aging, Cellular Senescence, and Cancer

            For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Stability and flexibility of epigenetic gene regulation in mammalian development.

              Wolf Reik (2007)
              During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences--transposons, imprinted genes and pluripotency-associated genes--in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                09 September 2014
                2014
                : 2
                : 49
                Affiliations
                Epigenetics Laboratory, Department of Anatomy, Howard University Washington, DC, USA
                Author notes

                Edited by: Jeff Schwartz, Griffith University, Australia

                Reviewed by: Abhijit Shukla, Harvard Medical School, USA; Sergio R. Ojeda, Oregon Health & Science University, USA

                *Correspondence: Antonei B. Csoka, Epigenetics Laboratory, Department of Anatomy, Howard University, 520 W St. NW, Mudd 431, Washington, DC 20059, USA e-mail: antonei.csoka@ 123456howard.edu

                This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental Biology.

                Article
                10.3389/fcell.2014.00049
                4207041
                25364756
                b42c9e04-1a89-4455-a7c1-81d13038d9aa
                Copyright © 2014 Kanherkar, Bhatia-Dey and Csoka.

                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) or licensor 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
                : 20 June 2014
                : 22 August 2014
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 191, Pages: 19, Words: 16756
                Categories
                Genetics
                Review Article

                epigenetics,human lifespan,disease,environment,diet,development
                epigenetics, human lifespan, disease, environment, diet, development

                Comments

                Comment on this article