Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death

Area of Science:

• Gerontology and Cardiovascular Medicine
• Molecular Biology and Aging
• Biochemistry and Cellular Metabolism

Background:

• Aging is a primary risk factor for cardiovascular diseases (CVD), involving complex molecular and cellular changes.
• Age-related cardiovascular decline is linked to oxidative stress, impaired autophagy, mitochondrial dysfunction, inflammation, and cardiac issues, often associated with Klotho deficiency.
• Klotho, an anti-aging protein, possesses antioxidant, anti-inflammatory, and cardio-protective properties, influencing calcium regulation, autophagy, and nitric oxide production.

Purpose of the Study:

• To review recent advancements in utilizing Klotho as a therapeutic strategy for age-related cardiovascular diseases (CVD).
• To summarize preclinical evidence supporting the role of Klotho in mitigating cardiovascular aging.
• To explore Klotho's impact on intracellular pathways relevant to cardiovascular health during aging.

Main Methods:

• Review of preclinical studies and scientific literature on Klotho's function in aging and cardiovascular health.
• Analysis of Klotho's molecular mechanisms, including its effects on oxidative stress, autophagy, and mitochondrial function.
• Investigation of Klotho's impact on vascular smooth muscle cells (VSMC) and endothelial function.

Main Results:

• Klotho deficiency is associated with multiple age-related cardiovascular complications.
• Klotho demonstrates protective effects against oxidative stress, inflammation, and endothelial dysfunction.
• Klotho influences vascular smooth muscle cell energetics and survival, suggesting a key role in cardiovascular maintenance.
• Klotho modulates calcium regulation and autophagy, crucial processes in cellular health and aging.

Conclusions:

• Klotho exhibits significant therapeutic potential for ameliorating age-related cardiovascular diseases (CVD).
• Preclinical evidence supports Klotho's multifaceted protective roles in the aging cardiovascular system.
• Further research into Klotho-based therapies could offer novel treatment options for cardiovascular aging.