Hypoxia and the Aging Cardiovascular System

Abstract

Older individuals represent a growing population, in industrialized countries, particularly those with cardiovascular diseases, which remain the leading cause of death in western societies. Aging constitutes one of the largest risks for cardiovascular diseases. On the other hand, oxygen consumption is the foundation of cardiorespiratory fitness, which in turn is linearly related to mortality, quality of life and numerous morbidities. Therefore, hypoxia is a stressor that induces beneficial or harmful adaptations, depending on the dose. While severe hypoxia can exert detrimental effects, such as high-altitude illnesses, moderate and controlled oxygen exposure can potentially be used therapeutically. It can improve numerous pathological conditions, including vascular abnormalities, and potentially slows down the progression of various age-related disorders. Hypoxia can exert beneficial effects on inflammation, oxidative stress, mitochondrial functions, and cell survival, which are all increased with age and have been discussed as main promotors of aging. This narrative review discusses specificities of the aging cardiovascular system in hypoxia. It draws upon an extensive literature search on the effects of hypoxia/altitude interventions (acute, prolonged, or intermittent exposure) on the cardiovascular system in older individuals (over 50 years old). Special attention is directed toward the use of hypoxia exposure to improve cardiovascular health in older individuals.

Figure 1.

Influences of stimulus parameters and condition of the subject (“resilience”) on the quality of the effects of hypoxia exposure. If the stimulus is mild enough, beneficial adaptations may be induced that in turn increase resilience. If the severity of the stimulus surpasses the organism’s tolerance capacity, harmful effects might arise.

Figure 2.

Different doses of hypoxia elicit differential effects. The dose thereby is a function of inspired oxygen, frequency, and duration of exposure. Acute exposure to hypoxia triggers molecular and systemic changes that can result in either beneficial adaptations or maladaptation (A). Accordingly, depending on the hypoxic dose (and individual vulnerabilities), intermittent hypoxia can have health-deteriorating or -promoting consequences (B).

Figure 3.

Physiological consequences of exposure to moderate hypoxia and modulation by age. Many factors determine physiological outcomes of hypoxia. Also age-related changes of the cardiovascular system modulate these outcomes. CO₂: carbon dioxide, NO: nitric oxide.