Targeting mitochondrial fitness as a strategy for healthy vascular aging

Abstract

Cardiovascular diseases (CVD) are the leading cause of death worldwide and aging is the primary risk factor for CVD. The development of vascular dysfunction, including endothelial dysfunction and stiffening of the large elastic arteries (i.e., the aorta and carotid arteries), contribute importantly to the age-related increase in CVD risk. Vascular aging is driven in large part by oxidative stress, which reduces bioavailability of nitric oxide and promotes alterations in the extracellular matrix. A key upstream driver of vascular oxidative stress is age-associated mitochondrial dysfunction. This review will focus on vascular mitochondria, mitochondrial dysregulation and mitochondrial reactive oxygen species (ROS) production and discuss current evidence for prevention and treatment of vascular aging via lifestyle and pharmacological strategies that improve mitochondrial health. We will also identify promising areas and important considerations (‘research gaps’) for future investigation.

Lifelong voluntary aerobic exercise prevents age‐ and Western diet‐ induced vascular dysfunction, mitochondrial oxidative stress and inflammation in mice

“…Consistent with this idea, we observed elevations in aortic mitochondria-specific superoxide across the lifespan in sedentary mice consuming normal chow, and associated tonic suppression of EDD, evidenced by restoration of EDD with the ex vivo application of a mitochondrial antioxidant (MitoQ) to isolated arteries (Gioscia-Ryan et al 2014). Together, these observations support the growing body of literature indicating that vascular mitochondria are an important source of reactive oxygen species bioactivity and oxidative stress in ageing arteries (Rossman et al 2020).…”

“…2013; Rossman et al . 2020). Consistent with this idea, we observed elevations in aortic mitochondria‐specific superoxide across the lifespan in sedentary mice consuming normal chow, and associated tonic suppression of EDD, evidenced by restoration of EDD with the ex vivo application of a mitochondrial antioxidant (MitoQ) to isolated arteries (Gioscia‐Ryan et al .…”

“…Together, these observations support the growing body of literature indicating that vascular mitochondria are an important source of reactive oxygen species bioactivity and oxidative stress in ageing arteries (Rossman et al . 2020).…”

“…Oxidative stress-and inflammation-driven signalling are important mediators of aortic stiffening via adverse remodelling of the arterial wall, though endothelial dysfunction and age-related increases in vasomotor tone are also likely to contribute (Lakatta & Levy, 2003;Zieman et al 2005;Soucy et al 2006;Fleenor et al 2012a). A growing body of literature suggests that dysregulated vascular mitochondria are an important source of oxidative stress in the setting of age-related vascular dysfunction (Davidson & Duchen, 2007;Widlansky & Gutterman, 2011;Kluge et al 2013;Gioscia-Ryan et al 2016;Rossman et al 2020).…”

Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage

“…Since ATP depletion and MitoSOX generation are related to mitochondrial dysfunction, WHC may regulate other mitochondrial functions. For example, mitochondrial fitness [ 30 ] is regulated by mitochondrial dynamic changes, such as mitochondrial fusion and fission. Detailed investigation of the mitochondrial fitness of breast cancer cells after WHC treatments would further increase our understanding.…”