2016
DOI: 10.18632/aging.101086
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Abstract: 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 neuro… Show more

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Cited by 37 publications
(30 citation statements)
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References 49 publications
(64 reference statements)
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“…More recent data indicate that protein restriction rather than calorie restriction is responsible for the increase in FGF21 in response to starvation [ 32 ]. In ApoE-deficient mice subjected to long-term caloric restriction, FGF21 decreased when compared with controls during the first 25 weeks of caloric restriction and then increased over the controls from 30 to 64 weeks [ 33 ]. Plasma FGF21 has also been reported to be upregulated in mice subjected to caloric restriction for 4–6.5 weeks [ 34 ].…”
Section: Discussionmentioning
confidence: 99%
“…More recent data indicate that protein restriction rather than calorie restriction is responsible for the increase in FGF21 in response to starvation [ 32 ]. In ApoE-deficient mice subjected to long-term caloric restriction, FGF21 decreased when compared with controls during the first 25 weeks of caloric restriction and then increased over the controls from 30 to 64 weeks [ 33 ]. Plasma FGF21 has also been reported to be upregulated in mice subjected to caloric restriction for 4–6.5 weeks [ 34 ].…”
Section: Discussionmentioning
confidence: 99%
“…However, in terms of abnormal p-tau accumulation induced by stress, conflicting results have been found. A mouse model of tauopathy subjected to long-term CR was shown to have decreased p-tau accumulation ( Rühlmann et al, 2016 ), and similar effects were observed in a transgenic model of AD that also underwent long-term CR ( Halagappa et al, 2007 ). In a mouse model of tauopathy exposed to shorter and gradually increasing periods of CR, in contrast, no observable differences in p-tau levels were found ( Brownlow et al, 2014 ).…”
Section: Alzheimer's Disease Stress and Taumentioning
confidence: 83%
“…The protocol was adapted to Wong et al [26] reporting no significant differences in the [ 18 F]FDG uptake in mice between fasted and non-fasted state [26]. Moreover, the present study was designed according to own previous studies [13,27] showing the neuroprotective effect of caloric restriction versus ad-libitum feeding in ApoE−/− mice. Similarly, interval fasting also caused neuroprotective effects.…”
Section: Pet/ct Imagingmentioning
confidence: 99%