20:T4df,The effect of advancing age on the chronobiology of testosterone (T) and luteinizing hormone (LH) secretion in healthy men was investigated. Twenty young (average age 30.4 yrs) and 14 elderly (average age 70.4 yrs) men underwent 10 min blood sampling for 25 hrs to evaluate the circadian periodicity of LH, LH pulse frequency, and T. Using cosinor regression analysis, young men were found to have a significant (p less than .05) circadian variation in LH pulse frequency, with slowing of LH pulses during the night (maximum slowing at 2230 hr). There was also a tendency for LH pulse amplitude to increase at night (p = .06) in young men. However, no significant circadian pattern in LH pulse frequency or amplitude was detected in the elderly men. Mean LH by radioimmunoassay (RIA) and bioassay did not vary over the 24-hr period in either age group. Both young and elderly men had significant circadian rhythms in serum T, although the rhythm in elderly men was considerably blunted and was shifted in time compared to the young. These data provide evidence for age-related changes in the circadian rhythms of LH pulse frequency and T secretion and suggest that the LHRH pulse generator loses its circadian rhythmicity with normal aging in men.21:T436,Sleep loss can severely impair the ability to perform, yet the ability to recover from sleep loss is not well understood. Sleep regulatory processes are assumed to lie exclusively within the brain mainly due to the strong behavioral manifestations of sleep. Whole-body knockout of the circadian clock gene Bmal1 in mice affects several aspects of sleep, however, the cells/tissues responsible are unknown. We found that restoring Bmal1 expression in the brains of Bmal1-knockout mice did not rescue Bmal1-dependent sleep phenotypes. Surprisingly, most sleep-amount, but not sleep-timing, phenotypes could be reproduced or rescued by knocking out or restoring BMAL1 exclusively in skeletal muscle, respectively. We also found that overexpression of skeletal-muscle Bmal1 reduced the recovery response to sleep loss. Together, these findings demonstrate that Bmal1 expression in skeletal muscle is both necessary and sufficient to regulate total sleep amount and reveal that critical components of normal sleep regulation occur in muscle.

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