OBJECTIVES: This study sought to define the effects of age and gender effects on the normal range of time domain heart rate variability (HRV) over nine decades in healthy subjects. BACKGROUND: Low HRV is considered an independent marker of mortality risk. However, the age-related decline in HRV may limit its predictive value, particularly in the elderly. Delineation of the range of HRV in healthy subjects over the life span is needed. Gender-related differences in HRV also need clarification. METHODS: We determined, according to decade, 24-h heart rate (HR) and HRV of 260 healthy subjects (10 to 99 years old; 112 male, 148 female) by means of five standard time domain measures: standard deviation of all normal sinus RR intervals over 24 h (SDNN), standard deviation of the averaged normal sinus RR intervals for all 5-mm segments (SDANN), mean of the standard deviations of all normal sinus RR intervals for all 5-min segments (SDNN index), root-mean-square of successive normal sinus RR interval difference (rMSSD) and the percentage of successive normal sinus RR intervals >50 ms (pNN50). RESULTS: 1) HRV decreased with aging, the pattern of change being measure dependent. HRV (SDNN and SDANN) decreased only very gradually, reaching 60% of baseline (second-decade values) by the tenth decade. With the SDNN index, HRV decreased linearly with aging, reaching 46% of baseline by the tenth decade. Using pNN50 and rMSSD, HRV decreased most rapidly, reaching 24% and 47% of baseline, respectively, by the sixth decade and then stabilized. 2) Using the SDNN index, rMSSD and pNN50, HRV of subjects >65 years old fell below published cutpoints for increased risk of mortality in 25%, 12% and 4%, respectively. 3) At age <30 years, HRV for all measures was lower in female than male subjects. Gender differences decreased at age >30 years and disappeared at age >50 years. 4) HR also declined with aging but much more slowly. HR at age <50 years was faster in female than in male subjects. Gender differences disappeared thereafter. CONCLUSIONS: 1) Using all measures, HRV of healthy subjects declines with aging, with measure-dependent patterns. 2) Using the SDNN index, rMSSD and pNN50, HRV of healthy subjects, particularly those >65 years old, may decrease to below levels associated with increased risk of mortality. 3) Gender influences HRV. Gender differences in HRV are age and measure dependent. 4) Age and gender also affect heart rate.