Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging.

The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway (CAP) and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This scenario strongly suggests that ANS imbalance can fuel inflammaging, now recognized as one of the most relevant risk factors for age-related disease development. Recent recommendations have increasingly highlighted the need for actionable strategies to improve the quality of life for older adults by identifying biomarkers that can be easily measured, even in asymptomatic individuals. We advocate for considering ANS imbalance as a biomarker of aging and inflammaging. Measures of ANS imbalance, such as heart rate variability (HRV), are relatively affordable, non-invasive, and cost-effective, making this hallmark easily diagnosable. HRV gains renewed significance within the aging research landscape, offering a tangible link between pathophysiological perturbations and age-related health outcomes.