Abstract Background Cardiac autonomic modulation (CAM) is clinically evaluated by measuring the Heart Rate Variability (HRV) parameters, related to sympathetic and parasympathetic efferences to the heart, with linear (L), nonlinear (NL), and time-varying (TV) mathematical methods. Recently, automatic calculation of the parasympathetic (PNSi), sympathetic (SNSi), and Baevsky’s stress (BSTRi) indexes [1,2], integrating some L and NL parameters, has become available for more synthetic assessment of CAM. This study aimed to evaluate in healthy subjects (HS) the normal range of PNSi, SNSi, and BSTRi and their physiological variations during daily activity (ACT) and Non-REM sleep (NREM), taking also into account aging-related changes. Methods 24-hour (H24) Holter ECG recordings of 87 HS, divided into three (Age1, Age2 and Age3) groups (16-34, 35-52, and 53-84 years old, respectively), were retrospectively analyzed with the Kubios software (version 4.0), which automatically calculates the PNSi, SNSi, and BSTRi [1], and time domain (TD), frequency domain (FD), NL and TV HRV parameters. HRV was calculated from H24 and short-term (2 minutes) intervals, selected during ACT and NREM. All HRV calculations were done after "detrending" with the "smooth priors" function (lambda=500). Statistical analysis was performed with SPSS 21. Results Average values of the three indexes and several independent L and NL parameters are summarized in Table 1. Average BSTRi values of each age group were not different between ACT and NREM, whereas significant (p<0.05) increments between Age3 and Age1 (during ACT) and between Age3 and both Age1 and 2 (during NREM and H24) were found. Average SNSi values were slightly above the normality range [1] during ACT, or normal (during NREM and H24). Average PNSi values were within the suggested normality range [1] with minimal aging-related variations. Significant aging-related decrement of the selected TD and FD parameters was found in all analysed conditions. Among NL parameters, the correlation dimension (D2) values showed significant aging-related decrement (H24 and NREM), while H24 and ACT sample entropy (SampEn) was lower in Age1 and Age2, compared with Age3 (p<0.05). An example (H24 analysis of Age3 data) of significant (p<0.01) correlation among the three indexes and the selected independent linear and non-linear parameters is shown in Figure 1. Conclusions In this study, a significant aging-related increment of BSTRi was found in all investigated conditions. PNSi and SNSi were always within the suggested normality range [1]. In spite of the significant changes of linear parameters consistent with the well-known aging-related decrement of HRV, the higher SampEn (and BSTRi) found in Age3 HS suggests that an "healthy elderly", is characterized by a more complex adaptation of CAM, likely mediated also by the observed moderate (healthy?) increment of physiological stress. However further investigation on a broader population is warranted.Table 1Figure 1