Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction

Hayashida, Takahiro; Komatsu, Toshimitsu; Henmi, Yasuko; Yanagihara-Ota, Kurumi; Kim, Ae Ra; Chiba, Takuya; Goto, Shinji; Chung, Hae Young; Shimokawa, Isao

doi:10.1111/j.1447-0594.2011.00692.x

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…Indeed our analysis showed significant higher levels of HSP chaperones in both the CU and AL, as compared to RES ( Supplementary Table 4 ). Corroborating our HSP-derived conclusion of AL being stressful compared to RES, livers from 30 % calorie**-were reported to generate significantly less reactive oxygen species and contain more reduced glutathione and SOD2, than AL rat livers [ 84 ].…”

Section: Discussionmentioning

confidence: 98%

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

Gat-Yablonski

Finka

Pinto

et al. 2016

Aging

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Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span.

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Section: Discussionmentioning

confidence: 98%

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

Gat-Yablonski

Finka

Pinto

et al. 2016

Aging

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“…Dietary restriction‐induced alterations of energy metabolism could affect mitochondrial respiration, reactive oxygen species (ROS) production, and redox regulation. In our study of male Wistar rats subjected to feeding every other day with 30% less food, hepatic mitochondrial ROS generation decreased after feeding (the first day), while it increased during fasting (the second day) 42 . This implied that when glucose was the primary energy source, ROS levels were low; when fasting, fatty acid oxidation and amino acid catabolism supplied intermediate metabolites to the tricarboxylic acid (TCA) cycle, respiratory chain, and gluconeogenesis, and ROS levels were as high as those in the AL group 42 .…”

Section: Foxo Transcription Factorsmentioning

confidence: 58%

“…In our study of male Wistar rats subjected to feeding every other day with 30% less food, hepatic mitochondrial ROS generation decreased after feeding (the first day), while it increased during fasting (the second day). 42 This implied that when glucose was the primary energy source, ROS levels were low; when fasting, fatty acid oxidation and amino acid catabolism supplied intermediate metabolites to the tricarboxylic acid (TCA) cycle, respiratory chain, and gluconeogenesis, and ROS levels were as high as those in the AL group. 42 Correspondingly, the ratio of the oxidized form of glutathione (GSSG) to its reduced form (GSH) increased during fasting because of higher GSSG levels.…”

Section: Metabolic and Mitochondrial Adaptation To Dietary Restrictionmentioning

confidence: 99%

“…42 This implied that when glucose was the primary energy source, ROS levels were low; when fasting, fatty acid oxidation and amino acid catabolism supplied intermediate metabolites to the tricarboxylic acid (TCA) cycle, respiratory chain, and gluconeogenesis, and ROS levels were as high as those in the AL group. 42 Correspondingly, the ratio of the oxidized form of glutathione (GSSG) to its reduced form (GSH) increased during fasting because of higher GSSG levels. Thus, we speculated that ROS levels and redox status in mitochondria in the DR group fluctuate during the feeding cycle under the DR regimen, even if feeding is performed every day.…”

Section: Metabolic and Mitochondrial Adaptation To Dietary Restrictionmentioning

confidence: 99%

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Mechanisms underlying retardation of aging by dietary energy restriction

Shimokawa

2023

Pathology International

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Moderate restriction of dietary energy intake, referred to here as dietary restriction (DR), delays aging and extends lifespan in experimental animals compared with a diet of ad libitum feeding (AL) control animals. Basic knowledge of the mechanisms underlying the effects of DR could be applicable to extending the healthspan in humans. This review highlights the importance of forkhead box O (FoxO) transcription factors downstream of the growth hormone‐insulin‐like growth factor 1 signaling in the effects of DR. Our lifespan studies in mice with heterozygous Foxo1 or Foxo3 gene knockout indicated differential roles of FoxO1 and FoxO3 in the tumor‐inhibiting and life‐extending effects of DR. Subsequent studies suggested a critical role of FoxO3 in metabolic and mitochondrial bioenergetic adaptation to DR. Our studies also verified hypothalamic neuropeptide Y (Npy) as a vital neuropeptide showing pleiotropic and sexually dimorphic effects for extending the healthspan in the context of nutritional availability. Npy was necessary for DR to exert its effects in male and female mice; meanwhile, under AL conditions, the loss of Npy prevented obesity and insulin resistance only in female mice. Overnutrition disrupts FoxO‐ and Npy‐associated metabolic and mitochondrial bioenergetic adaptive processes, causing the acceleration of aging and related diseases.

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Upregulation of cytochrome c oxidase subunit 6b1 (Cox6b1) and formation of mitochondrial supercomplexes: implication of Cox6b1 in the effect of calorie restriction

Kim

Mori

Komatsu

et al. 2015

AGE

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Calorie restriction (CR), a non-genetic intervention that promotes longevity in animals, may exert anti-aging effects by modulating mitochondrial function. Based on our prior mitochondrial proteome analysis, we focused on the potential roles of cytochrome c oxidase (Cox or Complex IV) subunit 6b1 on formation of mitochondrial supercomplexes comprised of Complex I, III, and IV. Blue native polyacrylamide gel electrophoresis followed by immunoblotting showed that the amount of Cox6b1 and the proportion of high molecular weight supercomplexes (SCs) comprised of Complexes I, III, and IV were increased in the liver of mice subjected to 30 % CR, compared with the liver of mice fed ad libitum. In in vitro experiments, in Cox6b1-overexpressing NIH3T3 (Cox6b1-3T3) cells, Cox6b1 was increased in the SC, III2IV1, and III2IV2 complexes and Cox was concomitantly recruited abundantly into the SC, compared with control (Con)-3T3 cells. The proportions of III2IV1, and III2IV2, relative to IV monomer were also increased in Cox6b1-3T3 cells. Cox6b1-3T3 cells showed increased oxygen consumption rates, Cox activity, and intracellular ATP concentrations, indicating enhanced mitochondrial respiration, compared with Con-3T3 cells. Despite the increased basal level of mitochondrial reactive oxygen species (ROS), cell viability after inducing oxidative stress was greater in Cox6b1-3T3 cells than in Con-3T3 cells, probably because of prompt activation of protective mechanisms, such as nuclear translocation of nuclear factor E2-related factor-2. These in vivo and in vitro studies show that Cox6b1 is involved in regulation of mitochondrial function by promoting the formation of SC, suggesting that Cox6b1 contributes to the anti-aging effects of CR.

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Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction

Abstract: The present study suggests that CR affects mitochondrial function and redox state through a pathway distinct from GH signaling.

Cited by 5 publications

References 41 publications

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

Mechanisms underlying retardation of aging by dietary energy restriction

Upregulation of cytochrome c oxidase subunit 6b1 (Cox6b1) and formation of mitochondrial supercomplexes: implication of Cox6b1 in the effect of calorie restriction

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