Aging impairs the neurovascular interface in the heart

Area of Science:

• Cardiovascular Biology
• Neuroscience
• Aging Research

Background:

• Aging is a primary risk factor for cardiovascular disease.
• The aging heart exhibits microcirculatory dysfunction and altered neurovascular interactions.
• Nerve density and function are critical for maintaining cardiac health.

Purpose of the Study:

• To investigate the impact of aging on the cardiac neurovascular interface.
• To identify molecular mechanisms underlying age-related changes in cardiac innervation.
• To explore the role of cellular senescence in cardiac denervation.

Main Methods:

• Assessed cardiac nerve density and vascular-derived neuroregulatory gene expression in aged versus young hearts.
• Utilized microRNA-145 (miR-145) knockout and endothelial semaphorin-3A (Sema3a) overexpression models.
• Investigated the effects of senescent cell removal on cardiac neurovasculature and function.

Main Results:

• Aging significantly reduces ventricular nerve density and dysregulates neuroregulatory genes.
• Down-regulation of miR-145 and up-regulation of Sema3a contribute to age-induced denervation.
• Removal of senescent cells restored nerve density, normalized Sema3a expression, and improved cardiac electrical stability.

Conclusions:

• Cellular senescence plays a critical role in age-associated cardiac denervation and dysfunction.
• Targeting senescence may offer a therapeutic strategy to mitigate age-related cardiovascular impairments.
• The miR-145/Sema3a axis is a key regulator of the cardiac neurovascular interface during aging.