Abstract
SummaryDeregulation 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.
Highlights
Aging is defined as a progressive decline of fitness over time, leading to death (Kirkwood & Holliday, 1979; Kirkwood, 2005)
Senescence and apoptosis may protect against tumor formation, the gradual accumulation of senescent cells will elicit tissue degeneration and organ dysfunction
While progressive age-related disturbances in homeostasis do correlate with a broad range of alterations in alternative splicing, the current challenge is to determine whether a specific splicing change contributes to the aging phenotype or is a consequence with little or no functional impact
Summary
Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. 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. 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.
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