Douglas R. Seals

Boulder, USA

Douglas R. Seals is the Distinguished Professor, Department of Integrative Physiology, University of Colorado Boulder. After receiving his PhD in applied exercise physiology, Dr Seals undertook postdoctoral studies at the Washington University School of Medicine, St Louis, and Associate Professorships at the University of Arizona, and University of Colorado Boulder. His recent awards include a National Institute on Aging MERIT Award (2004-current), and the Edward F. Adolph Distinguished Lecturer, American Physiological Society (2013). His research interests include investigation of changes in systolic blood pressure, large artery stiffness and vascular endothelial function that occur with physiological and pathophysiological aging; biological and lifestyle factors that influence cardiovascular aging; integrative (molecular to systemic) mechanisms that mediate cardiovascular aging and its modulation by biological and lifestyle factors; and interventions to improve adverse physiological changes associated with aging, including cardiovascular dysfunction, reductions in motor performance and impairments in cognitive function.

Monday 27 May 09:30

Cardiovascular aging and mitochondia function

Mitochondrial dysfunction plays a critical role in cardiovascular aging, with crosstalk between the mitochondria and cellular signaling implicated in both cardiac and vascular effects. It is already well established that age-related changes in mitochondria function are integral to pathological alterations in the heart. Added to this, recent studies have also implicated age-related changes in the mitochondria that are associated with vascular pathophysiological changes.

Studies have shown that mitochondria-derived oxidative stress is an important mechanism underlying the development of arterial endothelial dysfunction, a precursor to the development of cardiovascular disease. There is evidence that an excess of mitochondria-derived reactive oxygen species promotes adverse structural changes, notably an increase in collagen production and elastin degradation. Additionally, studies in animal models indicate that modulation of mitochondria-derived reactive oxygen species contributes to large elastic artery stiffening. Beyond these effects, mitochondria-derived reactive oxygen species have also been implicated in exacerbating and sustaining arterial inflammation. This may further contribute to arterial stiffening via a number of mechanisms, including induction of gene expression patterns that modulate structural protein turnover, impairment of vascular endothelial function, increases in vascular smooth muscle cell tone, and exacerbation of the local proinflammatory environment in the vascular wall.

Thus, the emerging evidence suggests the possibility of novel approaches to preventing cardiovascular disease. A key consideration is whether intervention with mitochondria-targeted antioxidants earlier in life could decrease aortic stiffness, and potentially, the risk of associated cardiovascular complications. Indeed, initial clinical studies in healthy older subjects suggest that this approach offers promise for treating age-related vascular dysfunction.


Key references

Gioscia-Ryan RA, Battson ML, Cuevas LM, Eng JS, Murphy MP, Seals DR. Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice. J Appl Physiol 2018;124:1194-202.

Rossman MJ, Santos-Parker JR, Steward CAC, Bispham NZ, Cuevas LM, Rosenberg HL, Woodward KA, Chonchol M, Gioscia-Ryan RA, Murphy MP, Seals DR. Chronic supplementation with a mitochondrial antioxidant (MitoQ) improves vascular function in healthy older adults. Hypertension 2018;71:1056-63.

LaRocca TJ, Martens CR, Seals DR. Nutrition and other lifestyle influences on arterial aging. Ageing Res Rev 2017;39:106-19.