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The emerging role of alternative splicing in senescence and aging

Mathieu Deschênes1, Benoit Chabot1

  • 1Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.

Aging Cell
|July 14, 2017
PubMed

Insights

Splicing defects in precursor mRNA impact cellular senescence and organismal aging. These changes in splicing factors and splice variants are linked to age-related diseases and the aging process.

Area of Science:

  • Molecular Biology
  • Genetics
  • Gerontology

Background:

  • Deregulation of precursor mRNA splicing is implicated in various illnesses.
  • Splicing machinery defects are linked to age-related chronic diseases, cellular senescence, and organismal aging.

Purpose of the Study:

  • To review recent advancements in understanding the role of splicing defects in aging.
  • To discuss the functional links between specific splice variants and senescence/aging.
  • To examine splicing defects in conditions like progeria, vascular aging, and Alzheimer's disease.

Main Methods:

  • Literature review of recent progress in splicing research related to aging.
  • Discussion of functional associations between splice variants (p53, IGF-1, SIRT1, ING-1) and senescence.
  • Review of splicing defects in specific age-related pathologies.

Main Results:

  • Defects in intron removal and splice site selection machinery contribute to cellular senescence and aging.
  • Specific splice variants of p53, IGF-1, SIRT1, and ING-1 are functionally associated with senescence and aging.
  • Splicing defects are observed in accelerated aging (progeria), vascular aging, and Alzheimer's disease.

Conclusions:

  • Changes in splicing factor activity and splice variant production significantly impact cellular senescence.
  • Altered splicing contributes to the overall aging phenotype.
  • Splicing deregulation is a key factor in age-related cellular dysfunction and disease.
Keywords:
RNARNA binding proteinsagingalternative splicingpre-mRNAsenescencesplice variantssplicing

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