title: Death by transposition - the enemy within?
abstract: Here we present and develop the hypothesis that the derepression of endogenous retrotransposable elements (RTEs) - "genomic parasites" - is an important and hitherto under-unexplored molecular aging process that can potentially occur in most tissues. We further envision that the activation and continued presence of retrotransposition contribute to age-associated tissue degeneration and pathology. Chromatin is a complex and dynamic structure that needs to be maintained in a functional state throughout our lifetime. Studies of diverse species have revealed that chromatin undergoes extensive rearrangements during aging. Cellular senescence, an important component of mammalian aging, has recently been associated with decreased heterochromatinization of normally silenced regions of the genome. These changes lead to the expression of RTEs, culminating in their transposition. RTEs are common in all kingdoms of life, and comprise close to 50% of mammalian genomes. They are tightly controlled, as their activity is highly destabilizing and mutagenic to their resident genomes.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Sedivy
authors.forename: Jill A
authors.initials: JA
authors.lastname: Kreiling
authors.forename: Nicola
authors.initials: N
authors.lastname: Neretti
authors.forename: Marco
authors.initials: M
authors.lastname: De Cecco
authors.forename: Steven W
authors.initials: SW
authors.lastname: Criscione
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Hofmann
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhao
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Peterson
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D006801:Humans; D018626:Retroelements / Q000235:genetics* / Q000502:physiology
chemical_list: D018626:Retroelements
keywords: aging; anti-retroviral therapy; cellular senescence; retrotransposition