Aging alters the circadian rhythm of glucose utilization in the suprachiasmatic nucleus.

Abstract

We examined the possibility that alterations in the timing of cyclic luteinizing hormone (LH) release during the middle age transition to infertility reflect differences in the circadian pattern of neural function in pacemaker areas of the hypothalamus, particularly the suprachiasmatic nucleus. We measured local cerebral glucose utilization (LCGU) because this parameter is an index of local brain function. We assessed LCGU in several brain areas of young and middle-aged ovariectomized estradiol-treated rats since LH surges are altered when rats are middle-aged. This alteration is correlated with changes in the diurnal pattern of neurotransmitter turnover in several hypothalamic areas that regulate cyclic LH release. The data demonstrate a circadian rhythm in glucose utilization in the dorsal and ventral suprachiasmatic nucleus. In young rats, LCGU increases within 1 hr of lights-on, increases further just prior to the initiation of the LH surge, and decreases within 1 hr oflights-off. In contrast, middle-aged rats show a more gradual increase in LCGU after lights-on, with no further increase prior to the LH surge, and a premature decrease during the afternoon and evening. The data suggest that changes in the circadian pattern of LCGU may be related to the alteration in timing and amplitude of estradiol-induced LH surges in middle-aged rats. Changes in the integrity of the biological clock or in the ability of the biological clock to entrain other neurochemical events may underlie the onset of altered cyclic reproductive function and the transition to irregular estrous cyclicity.The female reproductive system provides a unique model system to investigate mechanisms regulating endocrinedependent aging processes because changes that lead ultimately to infertility and the disappearance of reproductive cycles occur relatively early during adulthood. Thus, one can examine the regulation of aging processes in the virtual absence of age-related pathologies. The reproductive system of the aged female is characterized by the absence of both cyclic gonadotropin release and cyclic ovarian function. The period of total acyclicity and infertility follows a transitional phase during which ovulations occur at increasingly irregular intervals, the probability that a given cycle will be ovulatory is reduced, and the pattern of preovulatory gonadotropin surges and steroid hormone release is altered. Hypothalamic, pituitary, and ovarian functions are altered during the middleage transitional phase (1-4); however, the relative contribution of each to the transition to reproductive acyclicity is not well understood. The present study tested the hypothesis that a loss in precision of the circadian rhythm of hypothalamic function occurs during middle age, disrupting cyclic reproductive function.Reproductive cyclicity has a circadian basis and depends on the integrity of a neural pacemaker (5-7). Everett et al. (5) proposed that, in rodents, the timing and regularity of preovulatory gonadotropin surges are governed by diurnal ne...

Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice

“…2B). Together with the increase in the number of bouts of activity per day, this suggests that the amplitude of, coupling within, or output from the master circadian pacemaker is decreased by age, and is consistent with both in vitro and in vivo data collected from aging rodents [12,[23][24][25]35]. Recently, Aujard et al [2] reported that aging decreased the amplitude of the rhythm of firing rate in individual SCN neurons, suggesting that the effects of age on the circadian pacemaker are at the level of individual cells, although this does not necessarily preclude the possibility that coupling strength, either between individual pacemaking neurons or between the pacemaker and its outputs, is influenced by age.…”

“…These changes include decreases in the amplitude of many overt rhythms, including the rhythms of locomotor activity, drinking, body temperature, and the sleep-wake cycle [19,24,28,29,34], as well as corresponding decreases in the amplitudes of at least two rhythms of suprachiasmatic nucleus (SCN, site of the master mammalian circadian pacemaker) physiology: the rhythms of neural firing rate and of glucose uptake [25,31,35]. Additionally, species-specific changes in the free-running period in constant darkness (τ) are often observed [15,21,27,28] Aging does not alter the size of the SCN or the number of neurons it contains [14,36], suggesting that the effects of age are due to changes in the pacemaking capabilities of the neurons or the connections between them.…”

Alterations of Circadian Rhythmicity and Sleep in Aging: Endocrine Consequences

“…Morphological and neurochemical alterations consistent with both a reduced amplitude and an earlier phase of the circadian signal have been demonstrated in the SCN of older animals in some studies [8, 9]. However, other observations have raised the possibility that at least some older individuals maintain well-preserved circadian function into the later stages of adulthood [10].…”

Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8)

“…Second, c-Fos may not be the best marker to demonstrate reduced activity or hemispheric asymmetries. Reductions in the circadian fluctuations of glucose metabolism (Wise et al 1988), number of arginine-vasopressin (AVP) neurons (Roozendaal et al 1987), and in vitro neuronal activity (Satinoff et al 1993;Watanabe et al 1995) have been demonstrated with increased age. Third, split activity rhythms in hamsters are also accompanied by hemispheric asymmetries in levels of Per, Bmal, and AVP (de la .…”