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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
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Cytosolic DNA sensor IFI16 proteins: Potential molecular integrators of interactions among the aging hallmarks

Divaker Choubey1

  • 1Department of Environmental & Public Health Sciences University of Cincinnati, 160 Panzeca Way, P.O. Box 670056, Cincinnati, OH 45267, USA.

Ageing Research Reviews
|October 21, 2022
PubMed

Insights

IFI16 proteins integrate key aging hallmarks, influencing inflammation and cell growth. Understanding these interactions may enhance human health and lifespan.

Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Immunology

Background:

  • Human aging involves hallmarks like genomic instability, telomere attrition, and epigenetic alterations.
  • Interactions between these aging hallmarks are crucial but poorly understood.
  • Type I interferon (IFN) and IFI16 proteins are implicated in aging hallmark interactions.

Purpose of the Study:

  • To explore the role of IFI16 proteins in integrating aging hallmarks.
  • To elucidate the molecular mechanisms underlying aging hallmark interactions.
  • To assess the potential of targeting IFI16 for healthspan improvement.

Main Methods:

  • Review of existing literature on IFI16, aging hallmarks, and inflammation.
  • Analysis of IFI16's role in the cGAS-STING pathway and type I IFN expression.
  • Examination of IFI16's interaction with tumor suppressor proteins p53 and pRb.

Main Results:

  • IFI16 proteins are essential for cytosolic DNA-triggered type I IFN expression via the cGAS-STING pathway.
  • IFI16 proteins enhance the growth-inhibitory functions of p53 and pRb.
  • IFI16 proteins are implicated in multiple aging hallmarks.

Conclusions:

  • IFI16 proteins play a central role in integrating diverse aging hallmarks.
  • Targeting IFI16 interactions offers a potential strategy for mitigating aging-related decline.
  • Further research into IFI16 mechanisms could lead to interventions for improved human healthspan.
Keywords:
AMPKCellular senescenceCytosolic DNADNA-damageHyperglycemiaIFI16InterferonSenescence-associated secretory phenotypeTelomerecGAS-STING pathwayp53pRb

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