Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults

Rossman, Matthew J.; Santos‐Parker, Jessica R.; Steward, Chelsea A.C.; Bispham, Nina Z.; Cuevas, Lauren M.; Rosenberg, Hannah; Woodward, Kayla A.; Chonchol, Michel; Gioscia‐Ryan, Rachel A.; Murphy, Michael P.; Seals, Douglas R.

doi:10.1161/hypertensionaha.117.10787

Cited by 322 publications

(281 citation statements)

References 40 publications

Supporting

Mentioning

257

Contrasting

Order By: Relevance

“…Adequate concentrations of the cofactor BH 4 and the substrate tyrosine are essential for optimal activity of tyrosine hydroxylase, the rate-limiting enzyme required for NA synthesis (Kaufman, 1978;Moens & Kass, 2007). Increased oxidative stress is evident in primary ageing and contributes to age-associated cutaneous microvascular dysfunction (Rossman et al, 2018;Seals, Jablonski, & Donato, 2011). Tetrahydrobiopterin and tyrosine are susceptible to oxidation by reactive oxygen species (Li, Knowlton, Woodward, & Habecker, 2003) and are consequently reduced in aged skin (Lang, Holowatz, & Kenney, 2010).…”

Section: Ageingmentioning

confidence: 99%

Cold‐induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive

Alba

Castellani

Charkoudian

2019

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the topic of this review?This review presents an update and synthesis of normal mechanisms of human cutaneous vasoconstriction in response to cold stress. It then discusses conditions in which cutaneous vasoconstrictor responses are excessive or insufficient and cases in which cold‐induced vasoconstrictor responses become counter to maintaining thermal and haemodynamic homeostasis. What advances does it highlight?The review highlights our current understanding of the mechanisms that mediate alterations in cold‐induced cutaneous vasoconstriction in pathology and environmental extremes, which has important clinical implications for preventing cold‐ and cardiovascular‐related deaths. Abstract In humans, cold‐induced peripheral vasoconstriction is an essential element of body temperature regulation. Given that the thermoregulatory system responds rapidly to changes in skin temperature, sympathetically mediated cutaneous vasoconstriction represents a crucial ‘first line of defense’ against excessive reduction in body temperature. Sympathetic noradrenergic vasoconstrictor nerves cause a rapid decrease in skin blood flow, thus increasing the insulative capacity of the skin and decreasing heat loss from the body. Small changes in the activity of these nerves are also responsible for the subtle changes in skin blood flow that occur with normal daily activities or minor changes in environmental temperature. With ageing, hypertension and other conditions, the cutaneous reflex vasoconstrictor response can become excessive or insufficient. Healthy older adults have impaired reflex vasoconstriction, which may result in an impaired ability to defend body temperature in some circumstances. Hypertension is associated with augmented vasoconstriction, which could have pathological implications for left ventricular afterload in individuals already at risk for cardiovascular events. Finally, in some cases, the reflex vasoconstrictor response becomes distinctly counterproductive to its own goals of maintaining cardiovascular and thermoregulatory homeostasis. Examples include Raynaud's phenomenon, in which exaggerated vasoconstriction can produce ischaemia in the periphery, and the cutaneous vasoconstrictor response to therapeutic body cooling in severe hyperthermia, which can limit the heat exchange necessary to prevent serious heat illness.

show abstract

Section: Ageingmentioning

confidence: 99%

Cold‐induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive

Alba

Castellani

Charkoudian

2019

Experimental Physiology

View full text Add to dashboard Cite

show abstract

“…The clinical trial reconfirmed the safety and tolerability of MitoQ. [49] The 20 mg/d dose of MitoQ was well tolerated, and no treatmentrelated serious adverse events occurred. Even after 160 mg of acute administration, only a few mild adverse reactions occurred.…”

Section: Clinical Research Of Tpp-based Antioxidantsmentioning

confidence: 62%

“…In 2018, a successful clinical trial that demonstrated the effects of MitoQ to improve vascular function in healthy older adults. The clinical trial reconfirmed the safety and tolerability of MitoQ . The 20 mg/d dose of MitoQ was well tolerated, and no treatment‐related serious adverse events occurred.…”

Section: Pharmacokinetics and Clinical Research Of Tpp‐based Antioxidmentioning

confidence: 64%

Triphenylphosphonium (TPP)‐Based Antioxidants: A New Perspective on Antioxidant Design

Wang

Xiao

et al. 2020

ChemMedChem

View full text Add to dashboard Cite

Mitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria‐targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria‐targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000‐fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP‐based mitochondria‐targeted antioxidants. These provide theoretical and background support for the design of new anti‐oxidant.

show abstract

“…Mitochondrial targeted antioxidants have been shown to improve both large artery stiffness and EDD in old mice and older adults: however, in contrast to the results with TEMPOL described above, these improvements are largely independent of alterations in circulating and aortic cytokine production (Gioscia‐Ryan et al., , ; Rossman et al., ; Zinovkin et al., ). Mitochondrial targeted antioxidants decrease aortic ICAM in old mice (Zinovkin et al., ), and in rat endothelial cells scavenging of mitochondrial ROS attenuates NFκB activity and inflammatory cytokine production (Ungvari et al., ).…”

Section: Interventions To Ameliorate Age‐related Inflammation and Artmentioning

confidence: 97%

Inflammation as a mediator of arterial ageing

Trott

Fadel

2019

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the topic of this review?This review summarizes and synthesizes what is known about the contribution of inflammation to age‐related arterial dysfunction. What advances does it highlight?This review details observational evidence for the relationship of age‐related inflammation and arterial dysfunction, insight from autoimmune inflammatory diseases and their effects on arterial function, interventional evidence linking inflammation and age‐related arterial dysfunction, insight into age‐related arterial inflammation from preclinical models and interventions to ameliorate age‐related inflammation and arterial dysfunction. Abstract Advanced age is a primary risk factor for cardiovascular disease, the leading cause of death in the industrialized world. Two major components of arterial ageing are stiffening of the large arteries and impaired endothelium‐dependent dilatation in multiple vascular beds. These two alterations are major contributors to the development of overt cardiovascular disease. Increasing inflammation with advanced age is likely to play a role in this arterial dysfunction. The purpose of this review is to synthesize what is known about inflammation and its relationship to age‐related arterial dysfunction. This review discusses both the initial observational evidence for the relationship of age‐related inflammation and arterial dysfunction and the evidence that inflammatory autoimmune diseases are associated with a premature arterial ageing phenotype. We next discuss interventional and mechanistic evidence linking inflammation and age‐related arterial dysfunction in older adults. We also attempt to summarize the relevant evidence from preclinical models. Lastly, we discuss interventions in both humans and animals that have been shown to ameliorate age‐related arterial inflammation and dysfunction. The available evidence provides a strong basis for the role of inflammation in both large artery stiffening and impairment of endothelium‐dependent dilatation; however, the specific inflammatory mediators, the initiating factors and the relative importance of the endothelium, smooth muscle cells, perivascular adipose tissue and immune cells in arterial inflammation are not well understood. With the expansion of the ageing population, ameliorating age‐related arterial inflammation represents an important potential strategy for preserving vascular health in the elderly.

show abstract

Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults

Abstract: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.

Cited by 322 publications

References 40 publications

Cold‐induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive

Cold‐induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive

Triphenylphosphonium (TPP)‐Based Antioxidants: A New Perspective on Antioxidant Design

Inflammation as a mediator of arterial ageing

Contact Info

Product

Resources

About