Activation and degeneration during aging: A morphometric study of the human hypothalamus

Zhou, Jiang‐Ning; Swaab, D.F.

doi:10.1002/(sici)1097-0029(19990101)44:1<36::aid-jemt5>3.0.co;2-f

Cited by 47 publications

(22 citation statements)

References 90 publications

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“…These findings together with the present data show that the consistent alterations in the human circadian time system starts already in middle‐aged subjects, much earlier than generally thought. Supporting this idea, a number of circadian rhythms changes have been reported in middle‐aged human subjects [28].…”

Section: Discussionmentioning

confidence: 93%

Alterations in the circadian rhythm of salivary melatonin begin during middle‐age

Zhou

Liu

Heerikhuize

et al. 2002

Journal of Pineal Research

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To investigate whether free melatonin may be better suited to reveal age-related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take place. A total of 52 healthy volunteers participated in the study consisting of young, middle-aged, old and the oldest groups. In each subject, a total of 12 time-point salivary melatonin samples was taken over 24 hr. Of the 52 data sets, 51 exhibited significant circadian rhythm over 24 hr by using the base cosine function analysis to fit the data. A clear circadian rhythm of salivary melatonin was present in all age groups. The decline in nocturnal peak levels (amplitude) in salivary melatonin was found in old and the oldest subjects. Both the old and the oldest subjects showed an increased daytime (baseline) melatonin levels. The off-set melatonin levels were more than two times higher in the oldest group than that in the other groups indicating a delayed phase of salivary melatonin. Most strikingly, we found that a step-wise decrease in the circadian rhythms of saliva melatonin occurred early in life, around 40 yr of ages. The middle-aged subjects had only 60% of the amplitude of the young subjects. In addition, the middle-aged subjects showed the longest peak levels duration and the lowest daytime melatonin levels. The present study showed that the alterations in the circadian rhythms of salivary melatonin begin during middle-age. Our results showed that salivary melatonin measurement is a reliable, sensitive and easy method to monitor changes in the circadian rhythms of melatonin during the course of aging.

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Section: Discussionmentioning

confidence: 93%

Alterations in the circadian rhythm of salivary melatonin begin during middle‐age

Zhou

Liu

Heerikhuize

et al. 2002

Journal of Pineal Research

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“…Methodologic advances in the past decade, including the emergence of unbiased stereologic techniques, are credited with refuting the widely held belief that normal human aging involves extensive neuron loss (Morrison and Hof, 1997; Pakkenberg and Gundersen, 1997). Considerable structural plasticity remains in normal aged individuals, exemplified by signs of activation in several hypothalamic systems (Swaab, 1991; Mobbs, 1996; Zhou and Swaab, 1999). Similarly, the neuronal hypertrophy associated with reproductive senescence in women does not seem to be degenerative in nature.…”

Section: Discussionmentioning

confidence: 99%

Stereologic study of the hypothalamic infundibular nucleus in young and older women

Abel

Rance

2000

J. Comp. Neurol.

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Aging in women is associated with dramatic changes in neuronal morphology and neuropeptide gene expression in the medial basal hypothalamus. There is hypertrophy of neurons expressing substance P and neurokinin B gene transcripts in the infundibular (arcuate) nucleus, accompanied by increased tachykinin gene expression. In addition, gonadotropin-releasing hormone (GnRH) gene expression is increased in a separate subpopulation of neurons within the medial basal hypothalamus. In contrast, the number of neurons expressing proopiomelanocortin (POMC) mRNA in the infundibular nucleus of older women is decreased. To determine whether neuronal degeneration contributes to these phenomena, unbiased stereologic methods were used to compare the total number of infundibular neurons between groups of young (premenopausal) and older (postmenopausal) women. There was no significant difference in the total number of infundibular neurons between young (520,000 +/- 42,000 neurons, mean +/- SEM) and older women (505,000 +/- 51,000 neurons, mean +/- SEM). The mean volume of neuronal somata, however, was increased by 40% in the older women (young, 1,860 +/- 180 microm(3) vs. older, 2,610 +/- 230 microm(3), mean +/- SEM, P < 0.05). These data demonstrate that neuronal hypertrophy in older women is not accompanied by degeneration of the infundibular nucleus. We conclude that the loss of menstrual cyclicity in middle-aged women cannot be explained by loss of neurons within the hypothalamic control center for reproduction.

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“…It has been demonstrated for decades of years that the hypothalamic nuclei manifest heterogeneity in degeneration during aging in mammals [10] [16] [17] [18] [19]. The paraventricular nucleus (PVN) is responsible for stress response and is functional throughout the lifespan, maintaining its neuron number in senescence in humans [10] [16]. In contrast, the suprachiasmatic nucleus (SCN), the main controller of circadian rhythm, is decreased in its number of neurons during the aging process in humans and marmosets [10] [16] [18].…”

Section: Heterogeneity In Degeneration Of Hypothalamic Nuclei In Agingmentioning

confidence: 99%

“…Consequently, the influences from forebrain to the hypothalamus are random and various, changing from time to time. In this regard, if the hypothalamic aging resulted from the random and irregular plastic changes in the neural activities in forebrain, it would be difficult for the hypothalamus to specifically maintain the paraventricular nucleus (PVN) intact [10] [16] while only reduce the neurons in the suprachiasmatic nucleus (SCN) [10] [16] [18] and male preoptic sexually dimorphic nucleus (SDN-POA) [10] [16] [17] [19]. Therefore, it is as well deduced that the hypothalamic aging might result from the mechanisms other than those from the forebrain.…”

Section: The Dissociation Of the Forebrain Random Learning From The Pmentioning

confidence: 99%

The Peripheral Hypotheses of Hypothalamic Aging

Cai¹

2018

OALib

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It is well known that the hypothalamic changes in control of hormones determine the chronological sequence of aging in mammals. For decades, it has been demonstrated in humans that the hypothalamic nuclei manifest heterogeneity in degeneration during aging, with the neuron number decreasing in both the suprachiasmatic nucleus (SCN) and the preoptic sexually dimorphic nucleus (SDN-POA) in the process of senescence, while the neuron number remains unchanged in the paraventricular nucleus (PVN). Recently, it was newly hypothesized some peripheral mechanisms responsible for the senescent changes of the hypothalamic nuclei. It was proposed by Cai that the decrease in slow-wave sleep (SWS) caused the degeneration of the suprachiasmatic nucleus (SCN). Besides, when reviewing the proposal by the European people in television about the senescent pathway for male reproduction on the degeneration of hypothalamic preoptic area by the common knowledge of reduction of sperm production from adipose accumulation in the middle/old age, it was as well demonstrated that the reduced testosterone level from the increased body fat caused the degeneration of the male preoptic sexually dimorphic nucleus (SDN-POA). It seems both the activity-dependent and hormonal regulation of the neuronal numbers are involved in the mechanisms causing the senescence of the hypothalamic nuclei. It is further pointed out that the paraventricular nucleus (PVN) maintaining its neuronal number unchanged in aging may cause many cellular and molecular changes of aging from chronic stress. It is expected that these preliminary considerations could elicit more investigations on the other peripheral causes for the hypothalamic aging, such as the cholesterol, hypertension, and so on.

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Activation and degeneration during aging: A morphometric study of the human hypothalamus

Cited by 47 publications

References 90 publications

Alterations in the circadian rhythm of salivary melatonin begin during middle‐age

Alterations in the circadian rhythm of salivary melatonin begin during middle‐age

Stereologic study of the hypothalamic infundibular nucleus in young and older women

The Peripheral Hypotheses of Hypothalamic Aging

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