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Basic Science and Pathogenesis.

Carla Rocha Dos Santos1, Mackenzie J Barnett1, Ross A McDevitt1

  • 1National Institute on Aging/National Institutes of Health (NIA/NIH), Baltimore, MD, USA.

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Senolytic treatments with Quercetin (QRC) and Dasatinib (DAS) protected heart function and reduced anxiety in female rats but did not impact early vascular aging. A link between cardiac structure and attention performance was observed.

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Area of Science:

  • Gerontology
  • Cardiovascular Research
  • Neuroscience

Background:

  • Cardiovascular risk factors like high blood pressure and arterial stiffness contribute to cognitive decline.
  • Dahl salt-sensitive rats exhibit age-related vascular aging and cognitive impairment.
  • Previous studies showed senolytics QRC and DAS improved vascular aging and cognition in male rats.

Purpose of the Study:

  • To investigate the effects of QRC and DAS on vascular aging, heart parameters, and cognitive function in female DSS rats.
  • To test the hypothesis that QRC and DAS treatments would ameliorate vascular aging and improve cognition in female DSS rats.

Main Methods:

  • Six-month-old female DSS rats received placebo, QRC, or QRC+DAS for 6 months.
  • DAS was administered during the final 2 months of treatment.
  • Evaluated systolic blood pressure, arterial stiffness, cardiac function via echocardiography, cognitive function, and anxiety-like behaviors.

Main Results:

  • Neither QRC nor QRC+DAS affected blood pressure or arterial stiffness.
  • Both treatments improved cardiac function, increasing ejection fraction and fractional shortening.
  • QRC+DAS reduced relative left ventricle wall thickness; cognitive function did not differ significantly.
  • Both QRC and QRC+DAS groups showed reduced anxiety-like behavior.
  • Attention performance correlated with cardiac remodeling markers like left ventricle relative wall thickness and ejection fraction.

Conclusions:

  • Chronic senolytic treatments with QRC or QRC+DAS protected heart function and reduced anxiety in female DSS rats.
  • These treatments did not impact early vascular aging markers (blood pressure, arterial stiffness).
  • Observed correlations suggest a potential heart-brain interaction influencing attentional performance.