Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity.

An open pilot study on the safety and efficacy of melatonin in the treatment of insomniac patients was conducted in 22 subjects (16 females), mean +/- S.D. age 60.1 +/- 9.5 years. All patients received 3 mg of gelatin melatonin capsules per os daily for 6 months, 30 min before expected sleep time. Twenty of 22 patients were on benzodiazepine treatment and they continued this treatment for part of or for the entire melatonin administration period. Serum concentrations of prolactin, follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), or estradiol were measured by radioimmunoassay (RIA) in morning samples at the beginning and after 6 months of melatonin administration, and standard clinical laboratory tests for blood components were performed. Urinary 6-sulphatoxymelatonin (aMT6s) excretion was measured by RIA before treatment. Serum concentrations of prolactin, FSH, TSH, or estradiol did not exhibit changes after 6 months of melatonin administration, nor were any indications of hematologic or blood biochemistry alteration found. Melatonin augmented significantly the quality and duration of sleep, and decreased sleep latency and the number of awakening episodes, as assessed from sleep logs filled by the patients (first 21 days) and from structured interviews performed by incumbent physicians (up to 6 months). Estimates of next-day function (i.e., alertness in the morning and during the day) also improved significantly during melatonin treatment. The observed effect lasted for the entire period examined (up to 6 months), with 22 out of 22 patients showing improved sleep at the end of treatment. The urinary excretion of aMT6s before starting administration of melatonin correlated negatively and significantly with age, but not with the intensity of sleep the disorder or the outcome of treatment. In 13 of 20 patients taking benzodiazepines together with melatonin, benzodiazepine use could be stopped, and in another four patients, benzodiazepine dose could be decreased to 25-66% of the initial dose. The results of this open, subacute administration trial indicate that melatonin is a safe and useful treatment for sleep disturbances in middle-aged or elderly patients, either by itself or together with benzodiazepines.

Plasma epinephrine (EPI) and norepinephrine (NE) levels were examined among healthy men aged 20 to 25 and 60 to 65 years basally and during EPI infusions. On separate days, 14.3 and 42.9 ng/kg/min EPI was administered intravenously for 45 min. Although there was no age difference in venous EPI levels basally, the old had less increase during the EPI infusions. The plasma metabolic clearance rate of EPI was greater among the old men. Plasma NE levels were elevated among the elderly men, but both age groups had an increase in NE during the EPI 42.9 ng/kg/min infusion rate. During EPI infusions, the old men had less increase in systolic but not diastolic blood pressure or heart rate compared with the young men. The different pattern of change in venous EPI levels and increased metabolic clearance rate of EPI observed among the old men could, in part, explain diminished end-organ responsivity.