Aging and the hypothalamus: Research perspectives

Bernardis, Lee L.; Davis, Paul J.

doi:10.1016/0031-9384(95)02101-9

Cited by 21 publications

(8 citation statements)

References 154 publications

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“…In addition, lesions of the VMN in young rats resulted in increased body fat, glucose intolerance, hyperlipidemia, and reduced renal function. Conversely, ablation of the hypothalamic DMN in young rats resulted in decreased size and body fat, normal glucose and lipid metabolism, decreased risk of renal malfunction and lower IGF-I serum levels, all of which resembles the phenotype of a rodent under CR (Bernardis et al 1996). …”

Section: The Hypothalamus and The Endocrine Regulation Of Lifespanmentioning

confidence: 99%

Hypothalamic and dietary control of temperature-mediated longevity

Tabarean

Morrison

Marcondes

et al. 2010

Ageing Research Reviews

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Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area (POA) of the hypothalamus. This region receives and integrates peripheral, central and environmental signals and maintains a nearly constant core body temperature (Tcore) by regulating the autonomic and hormonal control of heat production and heat dissipation. Temperature sensitive neurons found in the POA are considered key elements of the neuronal circuitry modulating these effects. Nutrient homeostasis is also a hypothalamically regulated modulator of aging as well as one of the signals that can influence Tcore in homeotherms. Investigating the mechanisms of the regulation of nutrient and temperature homeostasis in the hypothalamus is important to understand how these two elements of energy homeostasis influence longevity and aging as well as how aging can affect hypothalamic homeostatic mechanisms.

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Section: The Hypothalamus and The Endocrine Regulation Of Lifespanmentioning

confidence: 99%

Hypothalamic and dietary control of temperature-mediated longevity

Tabarean

Morrison

Marcondes

et al. 2010

Ageing Research Reviews

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“…The pivotal role of the hypothalamus in promoting somatic senescence has been the core of several theories developed during the past three decades (Epstein, 1971;Dilman, 1976;Mobbs, 1989;Bernardis and Davis, 1996) that, incidentally, are still exerting a compelling interest in this field of research. It is not surprising therefore that this region of the brain has been searched for the presence of morphological alterations that might contribute to explain the functional and metabolic changes that occur during aging, namely the disruption of the hormonal milieu.…”

Section: Aging Of the Arcuate Nucleusmentioning

confidence: 99%

Arcuate nucleus of the hypothalamus: Effects of age and sex

Leal¹,

Andrade²,

Paula‐Barbosa³

et al. 1998

J. Comp. Neurol.

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The arcuate nucleus of the hypothalamus (ARN) is involved in a variety of functions known to be sexually dimorphic and altered by aging. Although the effects of sex and age on the synaptic organization and neurochemistry of the ARN have been extensively analyzed, data regarding sex-related differences and age-induced effects on the total number of neurons and volume of the ARN in adult and aged male and female rats are controversial. To address this issue, we have quantitatively analyzed the ARN of male and female Wistar rats aged 6 and 24 months. The optical fractionator, the optical rotator, and the Principle of Cavalieri were used as the estimators of the total number of neurons, mean nuclear volume of ARN neurons, and volume of the ARN, respectively. In addition, a Golgi study was carried out to analyze the dendritic trees of its neurons. We found that in young adult rats, the volume of the ARN is 0.9 mm3 in males and 0.7 mm3 in females, whereas the total number of neurons is 100 x 10(3) in males and 86 x 10(3) in females. ARN neurons of males and females have identical mean nuclear volumes, which we estimated to be 300 microm3. No significant effects of age were found in these parameters, both in males and in females. In adult rats, no sex-related differences were detected in the number of dendritic segments and in the total dendritic length, but the dendritic branching density and the spine density were greater in females than in males. In aged rats there was a significant reduction in the number of dendritic segments, in the total dendritic length, and in the branching and spine densities that, although evident in both sexes, was more marked in females. Our results show that the total number of neurons and the volume of the ARN are sexually dimorphic in adult and aged rats and that neither of these parameters is altered by aging. Conversely, aging induces regressive changes in the dendritic arborizations of ARN neurons of males and females and abolishes the sexual dimorphic pattern of their organization.

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“…Life‐long caloric restriction (CR) extends rodent life span by as much as 50% (Sohal and Weindruch, 1996), but 70 years after its physiological characterization, CR underlying mechanism remains unresolved. During this time, alternate methods of life span extension using the manipulation of neuroendocrine IGF‐1 signaling have been successfully implemented (Tatar et al, 2003; Wolkow et al, 2000) and other research perspectives suggesting that the hypothalamus plays a central role in aging have been growing (Bernardis and Davis, 1996). This has led many to speculate that CR protective effect is mediated by neuroendocrine mechanisms involving the IGF‐1 signaling pathway (Chiba et al, 2002; Wise, 1995; Nelson et al, 1995), however, experimental designs yielding information on the causal relationship between IGF‐1 and the anti‐aging action of CR have been lacking.…”

Section: Introductionmentioning

confidence: 99%

Age‐dependent loss of insulin‐like growth factor‐1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice

Yaghmaie

Saeed

Garan³

et al. 2006

Intl J of Devlp Neuroscience

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Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.

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Aging and the hypothalamus: Research perspectives

Cited by 21 publications

References 154 publications

Hypothalamic and dietary control of temperature-mediated longevity

Hypothalamic and dietary control of temperature-mediated longevity

Arcuate nucleus of the hypothalamus: Effects of age and sex

Age‐dependent loss of insulin‐like growth factor‐1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice

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