Lifespan extension by reduction of the growth hormone‐insulin‐like growth factor‐1 axis: relation to caloric restriction

Shimokawa, Isao; Higami, Yoshikazu; Tsuchiya, Tomoshi; Otani, Hiroshi; Komatsu, Toshimitsu; Chiba, Takuya; Yamaza, Haruyoshi

doi:10.1096/fj.02-0819fje

Cited by 113 publications

(83 citation statements)

References 17 publications

(5 reference statements)

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“…The GH/IGF-I and insulin system are also significantly altered following fasting and DR. However, differences in GH response and also in the degree of reduction in circulating IGF-I, IGFBP-3, insulin and in the increase of IGFBP-1 and insulin-sensitivity are evitable (Bartke and Turyn 2001;Bonkowski et al, 2009;Breese et al, 1991;Buschemeyer et al, 2010;Dunn et al, 1997;Escriva et al, 2007;Frystyk et al, 1999;Heijboer et al, 2005;Lee et al, 2010;Shimokawa et al, 2003;Wang et al, 2006;Zhao et al, 2010). Corticosteroids tend to increase more following fasting compared with DR (Sabatino et al, 1991;Shen et al, 2009); body temperature showed a steeper decrease following fasting compared with DR (Koizumi et al, 1992;Longo and Finch 2003a;Shen et al, 2009).…”

Section: Starvation and Stress Resistancementioning

confidence: 99%

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

2011

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Section: Starvation and Stress Resistancementioning

confidence: 99%

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

2011

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“…We do not dispute this but suggest that the changes in insulin signaling and sensitivity are secondary to the metabolic shift in these animals. Studies on long-lived transgenic mouse models indicate that the effects of DR are not fully explained by reduced growth hormone/IGF-1 axis activity [48][49][50][51].…”

Section: Spanmentioning

confidence: 99%

Metabolic Reprogramming in Dietary Restriction

Anderson

Weindruch²

2006

Interdisciplinary Topics in Gerontology

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It is widely accepted that energy intake restriction without essential nutrient deficiency delays the onset of aging and extends life span. The mechanism underlying this phenomenon is still unknown though a number of different, nonmutually exclusive explanations have been proposed. In each of these, different facets of physiology play the more significant role in the mechanism of aging retardation. Some examples include the altered lipid composition model, the immune response model and models describing changes in endocrine function. In this paper we propose the hypothesis that metabolic reprogramming is the key event in the mechanism of dietary restriction, and the physiological effects at the cellular, tissue and organismal level may be understood in terms of this initial event.Dietary restriction (DR) is the most successful intervention tested to date in mammals which greatly extends maximum life span and keeps animals 'younger longer' [1][2][3]. Consequently, any hypothesis about the etiology of aging must reconcile the effects of DR on aging. With increased knowledge of the mechanism of DR, we stand to gain a considerable insight into the process of aging.We propose that a change in the regulation of energy metabolism in response to DR is the primary step in the retardation of aging ( fig. 1). First we describe the evidence in support of metabolic reprogramming, a switch to an altered metabolic state, by DR in mice. Next we consider evidence for metabolic shifts in other model organisms where life span is extended by DR or by genetic manipulation. Then we focus on changes in mitochondrial energy metabolism with age and DR in mammals. Next we will explore the effects of altered mitochondrial function in the context of reactive oxygen species (ROS) generation and oxidative stress. Finally we describe the metabolic and morphological changes in white adipose tissue that we believe are a result of altered mitochondrial function. We propose that the activation of adipose tissue through metabolic reprogramming is critical to the mechanism of DR and that it leads to the changes in the animal physiology that are described in the models indicated above. Metabolic Reprogramming in Tissues from Dietary-Restricted AnimalsThe inverse linear relationship between calorie intake and life span in mice [4] suggests that genes central to energy metabolism may be critical in the underlying mechanism of DR in

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“…SREBP‐1c is the primary isoform expressed in insulin‐sensitive tissues such as the liver, WAT, and muscle (Shimano, 2009). Because CR further extended lifespan of two long‐lived strains, Ames dwarf mice and heterozygous antisense GH transgenic rats (Bartke et al ., 2001; Shimokawa et al ., 2003), we examined the role of GH/IGF‐1 in CR‐associated gene expression profiles of WAT in a previous study. Our findings suggested that CR‐associated alterations of gene expression were highly regulated, in a GH/IGF‐1‐independent manner.…”

Section: Introductionmentioning

confidence: 99%

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

et al. 2017

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SummaryCaloric restriction (CR) can delay onset of several age‐related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissue (WAT). In studies using genetically modified mice with extended lifespans, WAT characteristics influenced mammalian lifespans. However, molecular mechanisms underlying CR‐associated metabolic remodeling of WAT remain unclear. Sterol regulatory element‐binding protein‐1c (Srebp‐1c), a master transcription factor of fatty acid (FA) biosynthesis, is responsible for the pathogenesis of fatty liver (steatosis). Our study showed that, under CR conditions, Srebp‐1c enhanced mitochondrial biogenesis via increased expression of peroxisome proliferator‐activated receptor gamma coactivator‐1α (Pgc‐1α) and upregulated expression of proteins involved in FA biosynthesis within WAT. However, via Srebp‐1c, most of these CR‐associated metabolic alterations were not observed in other tissues, including the liver. Moreover, our data indicated that Srebp‐1c may be an important factor both for CR‐associated suppression of oxidative stress, through increased synthesis of glutathione in WAT, and for the prolongevity action of CR. Our results strongly suggested that Srebp‐1c, the primary FA biosynthesis‐promoting transcriptional factor implicated in fatty liver disease, is also the food shortage‐responsive factor in WAT. This indicated that Srebp‐1c is a key regulator of metabolic remodeling leading to the beneficial effects of CR.

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Lifespan extension by reduction of the growth hormone‐insulin‐like growth factor‐1 axis: relation to caloric restriction

Cited by 113 publications

References 17 publications

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

Metabolic Reprogramming in Dietary Restriction

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

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