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A Non-Channel Function of CFTR: Attenuating Mitochondrial Oxidative Stress and Cardiomyocyte Senescence via

Chun Chen1, Longtan Jiang2, Yuewen Qiu3

  • 1Department of Cardiovascular Medicine, Hengyang Medical School, The Changsha Central Affiliated Hospital, University of South China, Changsha, China.

Aging Cell
|June 23, 2026
PubMed

Insights

Cystic fibrosis transmembrane conductance regulator (CFTR) mitigates heart cell aging by reducing oxidative stress. USP45 deubiquitinates CFTR, protecting against age-related cardiovascular disease.

Area of Science:

  • Cardiovascular Biology
  • Cellular Aging
  • Ion Channel Function

Background:

  • Cardiomyocyte senescence is a key driver of cardiovascular disease.
  • The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiomyocyte senescence is not well understood.
  • CFTR expression and function in aging hearts require further investigation.

Purpose of the Study:

  • To investigate the role of CFTR in cardiomyocyte senescence.
  • To elucidate the molecular mechanisms by which CFTR influences cardiac aging.
  • To explore the potential of CFTR as a therapeutic target for age-related cardiovascular diseases.

Main Methods:

  • Analysis of atrial tissues from patients with varying durations of atrial fibrillation (AF).
  • Establishment of myocardial aging models using D-galactose in mice and cardiomyocytes.
  • Overexpression and knockdown studies of CFTR and USP45.
  • Measurement of senescence markers, oxidative stress indicators, and enzyme activities.

Main Results:

  • CFTR was downregulated in AF patients and negatively correlated with senescence markers (p16, p21, p53).
  • D-galactose induced senescence and decreased CFTR expression in aging models.
  • CFTR overexpression reduced senescence and oxidative stress, while enhancing antioxidant enzyme activity.
  • USP45 deubiquitinates CFTR, mitigating senescence and mitochondrial oxidative stress.

Conclusions:

  • CFTR plays a protective role against cardiomyocyte senescence and mitochondrial oxidative stress.
  • USP45-mediated deubiquitination of CFTR is a novel mechanism to combat cardiac aging.
  • Targeting the USP45-CFTR pathway may offer a therapeutic strategy for cardiovascular diseases.
Keywords:
CFTRUSP45cardiomyocyte senescencemitochondrial oxidative stress

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