Heart Rate Variability as a Proxy Measure for Oxidative Stress
Researchers here review the evidence for age-related changes in heart rate variability to be usefully reflective of age-related disruption to oxidative metabolism, the well-known oxidative stress observed in the tissues of older individuals. The presence of excessive oxidizing molecules in and around cells is harmful to cell function, and thus to tissue function and health. Oxidative stress is also linked to excessive inflammatory signaling, as one can cause the other. Unfortunately the mechanisms are sufficiently complex for suppressing oxidative stress to be a harder problem than simply consuming known antioxidants. Suppression of inflammation or engineering antioxidants to target specific cell structures has been more promising, but none of the existing solutions are all that great in terms of size of effect.
It is increasingly recognized that mild-to-moderate upregulation in the production of free radicals plays an important physiological role in cellular signaling and can trigger the mechanisms of antioxidant defense, supporting an adaptive response to various stressors. This so-called hormetic response results in the improvement of the functional metabolic reserves and is related to healthy aging as well as to the effects of anti-aging interventions. On the other hand, excessive production of free radicals contributes to the development of oxidative stress and leads to aging. Therefore, the search for biomarkers that would allow efficient assessment of redox homeostasis is of great importance in the monitoring of healthy aging.
We hypothesize that heart rate variability (HRV), which measures the changes in the time between successive R waves in an electrocardiogram (ECG), is largely defined by the activity of the redox homeostasis and, therefore, can be used as a biomarker of aging. Such reasoning is based on several lines of experimental evidence suggesting mechanistic links between the autonomic regulation and oxidative load. In this paper, the modulatory effect of well-characterized oxygen sensor H2S on cardiovascular function and pacemaker activity of the sinus node, the studies on the direct effects of free radicals on the functionality of adrenergic and cholinergic receptors, and demonstrated bidirectional interactions between the activity of the autonomic nervous system and immune response were introduced to support the hypothesis about the close interactions between the production of ROS and autonomic regulation and, thus, HRV. At the same time, further studies are needed to improve our understanding of the crosstalk between mitochondrial function and autonomic regulation.