Targeting Alternative Splicing for Reversal of Cellular Senescence in the Context of Aesthetic Aging

Plast Reconstr Surg. 2021 Jan 1;147(1S-2):25S-32S. doi: 10.1097/PRS.0000000000007618.


Cellular senescence is a state of stable cell cycle arrest that has increasingly been linked with cellular, tissue, and organismal aging; targeted removal of senescent cells brings healthspan and lifespan benefits in animal models. Newly emerging approaches to specifically ablate or rejuvenate senescent cells are now the subject of intense study to explore their utility to provide novel treatments for the aesthetic signs and diseases of aging in humans. Here, we discuss different strategies that are being trialed in vitro, and more recently in vivo, for the targeted removal or reversal of senescent cells. Finally, we describe the evidence for a newly emerging molecular mechanism that may underpin senescence; dysregulation of alternative splicing. We will explore the potential of restoring splicing regulation as a novel "senotherapeutic" approach and discuss strategies by which this could be integrated into the established portfolio of skin aging therapeutics.

MeSH terms

  • Aging / genetics
  • Alternative Splicing / drug effects*
  • Animals
  • Antioxidants / administration & dosage
  • Cellular Senescence / drug effects
  • Cellular Senescence / genetics*
  • Clinical Trials as Topic
  • Dasatinib / administration & dosage
  • Drug Evaluation, Preclinical
  • Esthetics
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / genetics
  • Humans
  • Models, Animal
  • Oligonucleotides / administration & dosage*
  • Protein Kinase Inhibitors / administration & dosage*
  • Quercetin / administration & dosage
  • Serine-Arginine Splicing Factors / antagonists & inhibitors
  • Serine-Arginine Splicing Factors / metabolism
  • Skin / cytology
  • Skin / drug effects
  • Skin Aging / drug effects*
  • Skin Aging / genetics


  • Antioxidants
  • Oligonucleotides
  • Protein Kinase Inhibitors
  • SRSF2 protein, human
  • Serine-Arginine Splicing Factors
  • Quercetin
  • Dasatinib