A characteristic of aging in humans, as well as in nonhuman primates, is the disruption and attenuation of many biological rhythms. A desynchronization or dampening of cyclical neuroendocrine patterns, such as the circulating melatonin rhythm, may help to explain age-related disturbances in sleep and daytime alertness. Although the cause of age-associated disruptions of biological rhythms is largely unknown, it may be partially due to cumulative neuronal damage of relevant brain areas by oxidative injury. If so, one would predict that dietary caloric restriction (CR), which is known to attenuate the level of oxidative damage, might help to maintain normal circadian hormone release and consolidated sleep/wake rhythms in aging primates. Our objectives were to determine if the 24-h release of melatonin and locomotor activity were affected by age, and if late-onset CR in adults prevented any age-related changes. To this end, we examined the 24-h plasma profiles of melatonin in catheterized young and old, male and female rhesus macaques (Macaca mulatta), which were subjected to either ad libitum (AL) feeding or late-onset CR (70% of AL) for 24 years. Additionally, we monitored locomotor activity in the same animals continuously for at least 2 weeks using Actiwatch recorders (Mini-Mitter Co., Inc., Sunriver, OR, USA), and analysed the resulting activity data using Sleepwatch software. The 24-h plasma melatonin rhythms were pronounced in all of the animals studied. However, the old males had significantly lower nighttime melatonin levels compared to the young males, regardless of diet. Moreover, the old males had significantly lower overall levels of activity and a significant increase in sleep fragmentation compared to the young males, which were not prevented with CR. Females showed no such age effects, but the average age of the old female group was younger than that of the males. Therefore, age-related decreases in nocturnal levels of circulating melatonin may contribute to increased sleep fragmentation in old macaques, which is not prevented or worsened by late-onset CR. Supported by: AG-023477, AG-19100, AG-19914, HD-29186, RR-00163 & RR-14451.
06 - 07 Nov 2006
Society for Endocrinology