Fasting and rapamycin: diabetes versus benevolent glucose intolerance

Blagosklonny, Mikhail V.

doi:10.1038/s41419-019-1822-8

Cited by 57 publications

(50 citation statements)

References 139 publications

(201 reference statements)

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“…4c, d). Consistent with these results, FMD combined with FDFT1 overexpressing had the most significant inhibitory effect on 18 F-FDG uptake in the in the xenograft model ( Fig. 4e, f).…”

Section: Resultssupporting

confidence: 85%

“…We confirmed these results in an in vivo xenograft model. Fasting dramatically inhibited 18 F-FDG uptake and attenuated tumor growth in this xenograft model. These results suggested that, similar to traditional cancer therapy, fasting can be a potential therapeutic Fig.…”

Section: Discussionmentioning

confidence: 74%

“…Fasting can also increase resistance to various oxidative stresses, such as acute surgical stress [12][13][14] . On the molecular level, fasting is not well understood but based on the data from studies on fasting-mediated longevity and stress resistance, it is thought to work at least in part through the inhibition of insulin/IGF-1/mTORC1 signaling [15][16][17][18] . Although fasting exerts extensive antitumor effects in numerous contexts, the impact of fasting on metabolic changes in CRC remains poorly studied.…”

mentioning

confidence: 99%

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Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

et al. 2020

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Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/ HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.

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“…4c, d). Consistent with these results, FMD combined with FDFT1 overexpressing had the most significant inhibitory effect on 18 F-FDG uptake in the in the xenograft model ( Fig. 4e, f).…”

Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

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Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

et al. 2020

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“…Rapamycin, (International Nonproprietary Name: sirolimus), is an inhibitor of mTOR, which results in an extended life span and prevents age-related diseases [157][158][159][160] by mediating SIRT1 expression [161,162]. mTOR is a serine-threonine kinase that plays a role in modulating cell survival, growth, proliferation, motility, protein synthesis and transcription [163] and inducing autophagy [164][165][166].…”

Section: Rapamycinmentioning

confidence: 99%

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

et al. 2020

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Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.

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“…Next, we investigated the involvement of apoptotic cell-mediated activation of mTORC1 in macrophages producing anti-inflammatory/tissue growth factors. The mTOR inhibitor rapamycin has been widely used to investigate mTORC1 function and signaling 48 – 50 . KCs that had phagocytosed apoptotic cells showed increased the expression of anti-inflammatory/tissue growth factors Il10 and Hbegf ; in contrast, the expression of these genes was reduced by rapamycin treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease

Cheng

Liu

et al. 2020

Cell Death Dis

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Damage to intestinal epithelial cells and the induction of cellular apoptosis are characteristics of inflammatory bowel disease. The C-type lectin receptor family member LSECtin promotes apoptotic cell clearance by macrophages and induces the production of anti-inflammatory/tissue growth factors, which direct intestinal repair in experimental colitis. However, the mechanisms by which the phagocytosis of apoptotic cells triggers the pro-repair function of macrophages remain largely undefined. Here, using immunoprecipitation in combination with mass spectrometry to identify LSECtin-interacting proteins, we found that LSECtin interacted with mTOR, exhibiting a role in activating mTORC1. Mechanistically, apoptotic cells enhance the interaction between LSECtin and mTOR, and increase the activation of mTORC1 induced by LSECtin in macrophages. Elevated mTORC1 signaling triggers macrophages to produce anti-inflammatory/tissue growth factors that contribute to the proliferation of epithelial cells and promote the reestablishment of tissue homeostasis. Collectively, our findings suggest that LSECtin-dependent apoptotic cell clearance by macrophages activates mTORC1, and thus contributes to intestinal regeneration and the remission of colitis.

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Fasting and rapamycin: diabetes versus benevolent glucose intolerance

Cited by 57 publications

References 139 publications

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease

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