Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice

Ma, Lina; Dong, Wen; Wang, Rong; Li, Yun; Xu, Baolei; Zhang, Jingshuang; Zhao, Zhigang; Wang, Yulan

doi:10.1016/j.brainresbull.2015.06.004

Cited by 80 publications

(54 citation statements)

References 33 publications

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“…Therefore, reduced mTOR and Tau-phosphorylation in the long-term CR-fed ApoE −/− mice can be most supposedly attributed to the activation of AMPK pathway by increased Fgf21. In parallel, Ma and coworkers showed that food restriction could lead to activation of SIRT1 and suppression of mTOR activation in mice and speculated that the SIRT1/mTOR signaling pathway may be involved in the neuroprotective effect of food restriction [46]. This view is supported by the study of Guo et al [47], which demonstrated that food restriction-induced SIRT/mTOR activation contributed to brain integrity.…”

Section: Discussionmentioning

confidence: 98%

Long-term caloric restriction in ApoE-deficient mice results in neuroprotection via Fgf21-induced AMPK/mTOR pathway

Rühlmann

Wölk

Blümel

et al. 2016

Aging

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Caloric restriction (CR) decelerates the aging process, extends lifespan and exerts neuroprotective effects in diverse species by so far unknown mechanisms. Based on known neuroprotective effects of fibroblastic growth factor 21 (Fgf21) we speculate that CR upregulates Fgf21, which phosphorylates neuronal AMP-activated protein kinase (AMPK), leading to a decrease of mammalian target of rapamycin (mTOR) signaling activity and an inhibition of tau-hyperphosphorylation. This in turn reduces the formation of neurofibrillary tangles, a neuropathological hallmark of Alzheimer's disease. ApoE-deficient mice (ApoE−/−), serving as a model of neurodegeneration, showed upon CR vs. ad libitum feeding increased Fgf21 levels in both, plasma and brain as well as higher phosphorylation of fibroblastic growth factor receptor 1c (Fgfr1c), extracellular signal-regulated kinases 1/2 (ERK1/2) and AMPK in brain, lower activity of mTOR and decreased Tau-phosphorylation. Finally, CR in ApoE−/− mice caused neuroprotection as indicated by a higher synaptic plasticity shown by immunohistochemical analysis with increased numbers of PSD95-positive neurons and a better cognitive performance as analyzed with Morris water maze test. These data provide substantial evidence that neuroprotection upon CR seems to be Fgf21-dependent. Further experiments are necessary to evaluate Fgf21 as a therapeutic tool to treat tauopathy for improvement of cognitive performance.

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Section: Discussionmentioning

confidence: 98%

Long-term caloric restriction in ApoE-deficient mice results in neuroprotection via Fgf21-induced AMPK/mTOR pathway

Rühlmann

Wölk

Blümel

et al. 2016

Aging

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“…Circadian rhythm and mTOR pathways are also dependent upon SIRT1 (14, 133, 134). SIRT1, a member of the sirtuin family, is a histone deacetylase (4, 56, 59, 67, 135–138) that can transfer acetyl groups from ε-N-acetyl lysine amino acids on the histones of DNA to control transcription.…”

Section: Circadian Clock Genesmentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

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BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

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“…In endothelial cells exposed to oxidized low density lipoproteins that can lead to atherosclerosis, SIRT1 activity is increased in conjunction with AMPK that leads to autophagy and promotes cellular protection (86). SIRT1 activation of autophagy also involves the inhibition of other pathways such as the mechanistic target of rapamycin (mTOR) (33, 101, 111, 112). SIRT1 can have an inverse relationship with mTOR in embryonic stem cells (57, 113).…”

Section: Sirt1 Stem Cells Autophagy and Apoptosismentioning

confidence: 99%

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

Maiese¹

2017

CNR

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Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction. SIRT1 is vital in determining the course of stem cell development and the survival, metabolism, and life span of differentiated cells that are overseen by both autophagy and apoptosis. SIRT1 interfaces with a number of pathways that involve forkhead transcription factors, mechanistic of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Wnt1 inducible signaling pathway protein 1 (WISP1) such that the level of activity of SIRT1 can become a critical determinant for biological and clinical outcomes. The essential fine control of SIRT1 is directly tied to the world of non-coding RNAs that ultimately oversee SIRT1 activity to either extend or end cellular survival. Future studies that can further elucidate the crosstalk between SIRT1 and non-coding RNAs should serve well our ability to harness the power of SIRT1 and non-coding RNAs for the treatment of vascular disorders.

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Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice

Cited by 80 publications

References 33 publications

Long-term caloric restriction in ApoE-deficient mice results in neuroprotection via Fgf21-induced AMPK/mTOR pathway

Long-term caloric restriction in ApoE-deficient mice results in neuroprotection via Fgf21-induced AMPK/mTOR pathway

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

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