Repurposing digoxin for geroprotection in patients with frailty and multimorbidity

Helena Lee*, Daisy Wilson, Karina V Bunting, Dipak Kotecha, Thomas Jackson

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

The geroscience hypothesis proposes biological hallmarks of ageing are modifiable. Increasing evidence supports targeting these hallmarks with therapeutics could prevent and ameliorate age-related conditions - collectively termed "geroprotector drugs". Cellular senescence is a hallmark with considerable potential to be modified with geroprotector drugs. Senotherapeutics are drugs that target cellular senescence for therapeutic benefit. Repurposing commonly used medications with secondary geroprotector properties is a strategy of interest to promote incorporation of geroprotector drugs into clinical practice. One candidate is the cardiac glycoside digoxin. Evidence in mouse models of pulmonary fibrosis, Alzheimer's disease, arthritis and atherosclerosis support digoxin as a senotherapeutic agent. Proposed senolytic mechanisms are upregulation of intrinsic apoptotic pathways and promoting intracellular acidification. Digoxin also appears to have a senomorphic mechanism - altering the T cell pool to ameliorate pro-inflammatory SASP. Despite being widely prescribed to treat atrial fibrillation and heart failure, often in multimorbid older adults, it is not known whether digoxin exerts senotherapeutic effects in humans. Further cellular and animal studies, and ultimately clinical trials with participation of pre-frail older adults, are required to identify whether digoxin has senotherapeutic effect at low dose. This paper reviews the biological mechanisms identified in preliminary cellular and animal studies that support repurposing digoxin as a geroprotector in patients with frailty and multimorbidity.

Original languageEnglish
Article number101860
Number of pages9
JournalAgeing Research Reviews
Volume86
Early online date20 Jan 2023
DOIs
Publication statusPublished - 1 Apr 2023

Bibliographical note

Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.

Keywords

  • Cardiac glycosides
  • Digoxin
  • Senolytic
  • Senotherapeutic
  • Geroscience
  • Geroprotector drug

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