title: Aging: Somatic Mutations, Epigenetic Drift and Gene Dosage Imbalance.
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.
authors.affiliation: Institute Jacques Monod, Paris, France and Université Paris Diderot, Paris, France. Electronic address: reiner.veitia@ijm.fr.
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
authors.affiliation: Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Diddahally R
authors.initials: DR
authors.lastname: Govindaraju
authors.affiliation: Laboratory Complex Systems and Matter, Université Paris Diderot, Paris, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bottani
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Birchler
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D044127:Epigenesis, Genetic; D018628:Gene Dosage; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*
keywords: dosage imbalance; epigenetic clock; epigenetic drift; genomic integrity; mutational load; senescence