The emerging role of alternative splicing in senescence and aging

Aging Cell. 2017 Oct;16(5):918-933. doi: 10.1111/acel.12646. Epub 2017 Jul 13.

Abstract

Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype.

Keywords: RNA; RNA binding proteins; aging; alternative splicing; pre-mRNA; senescence; splice variants; splicing.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Alternative Splicing*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Animals
  • Cellular Senescence / genetics
  • Exons
  • Gene Expression Regulation, Developmental
  • Humans
  • Inhibitor of Growth Protein 1 / genetics
  • Inhibitor of Growth Protein 1 / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Introns
  • Progeria / genetics*
  • Progeria / metabolism
  • Progeria / physiopathology
  • RNA Precursors / genetics*
  • RNA Precursors / metabolism
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • ING1 protein, human
  • Inhibitor of Growth Protein 1
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Insulin-Like Growth Factor I
  • SIRT1 protein, human
  • Sirtuin 1