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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Related Experiment Video

Updated: Jul 10, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

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Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging.

Thomas Brochard1, Rebecca L McIntyre2, Riekelt H Houtkooper3

  • 1Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.

Ageing Research Reviews
|November 20, 2023
PubMed
Summary
This summary is machine-generated.

Nucleoside reverse transcriptase inhibitors (NRTIs) show promise in slowing aging by targeting multiple aging hallmarks. These drugs may reduce DNA damage, improve protein stability, and decrease inflammation, potentially combating age-related diseases.

Keywords:
AgingGeroprotectorsInterventionMitohormesisNRTIs

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Area of Science:

  • Gerontology and pharmacology
  • Molecular and cellular biology
  • Drug repurposing

Background:

  • Aging is a major risk factor for numerous diseases.
  • Geroprotectors aim to combat aging mechanisms and reduce age-related disease incidence.
  • Nucleoside reverse transcriptase inhibitors (NRTIs) are approved for cancer and HIV treatment.

Purpose of the Study:

  • To explore the potential of repurposing NRTIs as geroprotectors.
  • To investigate the molecular, organellar, and cellular mechanisms by which NRTIs may slow aging.
  • To evaluate NRTIs' impact on hallmarks of aging.

Main Methods:

  • Review of recent studies on NRTIs and aging.
  • Analysis of NRTIs' effects on LINE-1 elements (Genomic Instability).
  • Investigation of NRTIs' impact on mitochondrial and cytosolic translation (Loss of Proteostasis).
  • Examination of NRTIs' effects on inflammasome activation (Altered Intercellular Communication).

Main Results:

  • NRTIs repress LINE-1 elements, reducing DNA damage and improving Genomic Instability.
  • NRTIs inhibit mitochondrial translation, activate ATF-4, suppress cytosolic translation, and extend lifespan in worms, relating to Loss of Proteostasis.
  • NRTIs inhibit P2X7-mediated inflammasome activation, reducing inflammation and improving Altered Intercellular Communication.

Conclusions:

  • NRTIs exhibit multifaceted mechanisms targeting key hallmarks of aging.
  • Repurposing NRTIs offers a promising strategy to combat aging and age-related diseases.
  • Future research must balance NRTI benefits against potential toxic side effects, possibly via hormesis.