Hypothalamic mechanisms of ageing and of specific age pathology—III. Sensitivity threshold of hypothalamo-pituitary complex to homeostatic stimuli in energy systems

Dilman, V.M.; Bobrov, Ju.F.; Остроумова, М Н; Lvovich, E.G.; Vishnevsky, A. S.; Anisimov, Vladimir N.; Vasiljeva, I.A.

doi:10.1016/0531-5565(79)90032-9

Cited by 33 publications

(3 citation statements)

References 53 publications

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“…Historically, one of the earliest ideas suggesting that the aging process stems from a progressive loss of hypothalamic sensitivity and homeostatic imbalance came from studies conducted in aging rodents that are corroborated with clinical conditions in humans ( 21 ). In a series of studies, Dilman and Anisimov examined changes in the thresholds of sensitivity in three major hypothalamic-pituitary-end-organ axes, namely, the reproductive, stress adaptive, and energy/thyroid systems ( 39 , 40 ), II and III. In a hemi-castrated rat model, in which compensatory hypertrophy of the contralateral ovary can be investigated, the dose of exogenously administered estrogen required to suppress the compensatory effect increases as age advances from 1-month-old to 28-month-old rats.…”

Section: The Aging Hypothalamus: Gradual Loss Of Homeostatic Regulatimentioning

confidence: 99%

“…When the adaptive homeostat (adrenal axis) and the energy homeostat (growth hormone, fatty acid, and glucose metabolism) were studied using their respective feedback regulators (dexamethasone, insulin, free fatty acids, and glucose, respectively), thresholds of the hypothalamic sensitivity were raised toward these agents in both aging rodents and humans ( 39 , 40 ), II and III. However, opposite effects were observed in the dopaminergic neuron-lactotroph-prolactin axis, presumably due to the fact that this axis is normally under inhibitory regulation ( 39 , 40 ), IV. These observations established the concept that physiological aging stems from a progressive loss of sensitivity of the hypothalamus toward their respective feedback regulators and provided experimental evidence for the neuroendocrine theory of aging ( 20 , 42 ).…”

Section: The Aging Hypothalamus: Gradual Loss Of Homeostatic Regulatimentioning

confidence: 99%

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Maintenance of Homeostasis in the Aging Hypothalamus: The Central and Peripheral Roles of Succinate

2015

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Aging is the phenotype resulting from accumulation of genetic, cellular, and molecular damages. Many factors have been identified as either the cause or consequence of agerelated decline in functions and repair mechanisms. The hypothalamus is the source and a target of many of these factors and hormones responsible for the overall homeostasis in the body. With advanced age, the sensitivity of the hypothalamus to various feedback signals begins to decline. In recent years, several aging-related genes have been identified and their signaling pathways elucidated. These gene products include mTOR, IKK-β/NF-κB complex, and HIF-1α, an important cellular survival signal. All of these activators/modulators of the aging process have also been identified in the hypothalamus and shown to play crucial roles in nutrient sensing, metabolic regulation, energy balance, reproductive function, and stress adaptation. This illustrates the central role of the hypothalamus in aging. Inside the mitochondria, succinate is one of the most prominent intermediates of the Krebs cycle. Succinate oxidation in mitochondria provides the most powerful energy output per unit time. Extra-mitochondrial succinate triggers a host of succinate receptor (SUCN1 or GPR91)-mediated signaling pathways in many peripheral tissues including the hypothalamus. One of the actions of succinate is to stabilize the hypoxia and cellular stress conditions by inducing the transcriptional regulator HIF-1α. Through these actions, it is hypothesized that succinate has the potential to restore the gradual but significant loss in functions associated with cellular senescence and systemic aging.

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Section: The Aging Hypothalamus: Gradual Loss Of Homeostatic Regulatimentioning

confidence: 99%

Section: The Aging Hypothalamus: Gradual Loss Of Homeostatic Regulatimentioning

confidence: 99%

Maintenance of Homeostasis in the Aging Hypothalamus: The Central and Peripheral Roles of Succinate

2015

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“…Deleterious histological abnormalities in testes were also reported. By normal aging, a decline in the sensitivity of the hypothalamus to feedback regulators occurs resulting in a progressive loss of homeostasis and alteration in the hormone production (Dilman et al, 1979). The weakening in the cellular antioxidant milieu in male reproductive system associated with aging was reported to inhibit the sperm axonemal phosphorylation resulting in increasing the number of immotile sperms (Desai et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Astragalus membranaceus and Punica granatum alleviate infertility and kidney dysfunction induced by aging in male rats

Alshinnawy¹,

El‐Sayed²,

Taha³

et al. 2020

Turk J Biol

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Introduction Infertility affects up to 20% of couples globally (Pan et al., 2018). The risk of poor reproductive insufficiency in males increases at >35 years old due to age-related changes in aged males including high incidence of systemic diseases and infections, vascular insufficiency, reduced levels of sex hormones, mutations, disorders in the architecture of testes, and oxidative stress (Azenabor et al., 2015; Ilacqua et al., 2018). In men over 35 years old, negative changes in sperm quality are reported and become more pronounced with age over 40 years (Rosiak-Gill et al., 2019). By aging, deterioration in semen quality is observed in the ejaculate volume, sperm count, motility, vitality and morphology (Harris et al., 2011). Furthermore, aging is associated with loss of kidney function marked with progressive reductions in renal blood flow and glomerular filtration rate (GFR). The decline in GFR is attributed to reductions in glomerular capillary flow rate, glomerular capillary ultrafiltration coefficient, and afferent arteriolar resistance (Weinstein and Anderson, 2010). These changes lead to loss of renal mass; stiffness of afferent arterioles, sclerosis of glomeruli, and tubulointerstitial fibrosis (Yoon and Choi, 2014). Aging is associated with altered activity and responsiveness to vasoactive stimuli; responses to vasoconstrictor stimuli are enhanced, while vasodilatory responses are impaired. These changes may predispose the older kidney to acute and progressive chronic kidney injury (Weinstein and Anderson, 2010). Therefore, targeting the pathological changes associated with male infertility and kidney dysfunctions could reverse these aging-induced perturbations. Astragalus membranaceus is a Chinese medicinal herb used to treat various diseases and is marketed as life-prolonging extracts for human use in China (Liu et al., 2017). The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins (Auyeung et al., 2016). The components of Astragalus membranaceus extract can increase telomerase activity, and has antiinflammatory,

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Biological Interactions of Aging and Carcinogenesis

Anisimov

Cancer Treatment and Research

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Hypothalamic mechanisms of ageing and of specific age pathology—III. Sensitivity threshold of hypothalamo-pituitary complex to homeostatic stimuli in energy systems

Cited by 33 publications

References 53 publications

Maintenance of Homeostasis in the Aging Hypothalamus: The Central and Peripheral Roles of Succinate

Maintenance of Homeostasis in the Aging Hypothalamus: The Central and Peripheral Roles of Succinate

Astragalus membranaceus and Punica granatum alleviate infertility and kidney dysfunction induced by aging in male rats

Biological Interactions of Aging and Carcinogenesis

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