Aging: Somatic Mutations, Epigenetic Drift and Gene Dosage Imbalance. Issue 4 (April 2017)

• Record Type: Journal Article
• Authors: Veitia, Reiner A.; Govindaraju, Diddahally R.; Bottani, Samuel; Birchler, James A.
• Is Part Of: Trends in cell biology. Volume 27:Issue 4(2017)
• Page Start: 299
• Page End: 310
• Publication Date: 2017-04
• Subjects: mutational load -- epigenetic drift -- genomic integrity -- dosage imbalance -- senescence -- epigenetic clock; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2016.11.006
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Aging involves a progressive decline of metabolic function and an increased incidence of late-onset degenerative disorders and cancer. To a large extent, these processes are influenced by alterations affecting the integrity of genome architecture and, ultimately, its phenotypic expression. Despite the progress made towards establishing causal links between genomic and epigenomic changes and aging, mechanisms underlying metabolic dysregulation and age-related phenotypes remain obscure. Here, we present a model linking genome-wide changes and their age-related phenotypic consequences via the alteration of macromolecular complexes and cellular networks. This approach may provide a better understanding of the dynamically changing genome–phenome map with age, but also deeper insights to developing more targeted therapies to prevent and/or manage late-onset degenerative disorders as well as decelerate aging. Trends: Aging is a progressive phenomenon influenced by genetic and epigenetic alterations in interaction with the environment. The aging process is characterized by nine hallmarks that bear consequences at the molecular, cellular, tissue, and organismal levels. A perturbation of the crosstalk within the triangle genome, epigenome and macromolecular complexes may explain several hallmarks of aging. Experimental and clinical interventions can modulate aging and increase either lifespan or healthy aging.