Good, Bad, Mobile Elements: Genome’s Most Successful “Parasites” as Emerging Players in Cell and Organismal Aging

Maurizio      Cardelli; Francesca      Marchegiani

Abstract

The biological bases of cellular and organismal aging are thought to involve, among others, basic stress response mechanisms. In this field an increasing amount of evidence, in recent years, point towards an important role of endogenous retroelements. During evolution these mobile genetic elements interpreted the dual role of selfish genomic parasites and useful “boosters” of genomic evolution. Similarly, in living cell these elements have an important role in stress response and in generating neuronal plasticity, but studies on in vitro cell cultures and animal models show that their excessive activation or misregulation may lead to DNA damage and cell senescence, and can trigger both innate immunity and a pro-inflammatory response. Being cell senescence, somatic DNA damage and inflammation three supposed key processes in human aging, and observing that several intracellular mechanisms normally controlling the activation of retroelements show a tendency to fade at late ages, a possible role of endogenous retroelements in organismal senescence is taken in consideration. A better knowledge of the basic mechanisms linking stress response, activation of endogenous retroelements and age-related cell/tissue alterations could not only help us gain a better understanding of the basic mechanisms of aging, but will also allow the experimentation of new therapeutic targets for different age-related diseases.

Keywords: Aging, senescence, stress, retrotransposon, retroelement, antagonistic pleiotropy, hormesis, innate immunity, DNA damage, inflammation