The activation of NF-κB through Akt-induced FOXO1 phosphorylation during aging and its modulation by calorie restriction

Kim, Dae Hyun; Kim, Ji Young; Yu, Byung Pal; Chung, Hae Young

doi:10.1007/s10522-007-9114-6

Cited by 102 publications

(86 citation statements)

References 38 publications

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“…The plasma insulin level increased in aged rats compared with the young group, as we previously showed ( Fig. 4b; Kim et al 2008). Ferulate effectively reduced the age-related increase of plasma insulin level, which corresponded with IRS activation (Fig.…”

Section: Effect Of Ferulate On Insulin Signaling and Plasma Insulin Lsupporting

confidence: 81%

“…In aged rats, Akt activity, as shown by phosphorylated forms, was upregulated, and its upstream signaling pathway corresponded with this upregulation. In a previous study, we showed that an enhanced Akt/PI3K signaling pathway in aged rats by calorie restriction has a potent anti-aging effect (Kim et al 2008). Several studies have reported on various Akt expression for 10 days, respectively).…”

Section: Discussionmentioning

confidence: 94%

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Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Choi

Kim

Lee

et al. 2011

AGE

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Ferulate (4-hydroxy-3-methoxycinnamic acid) is a well-known phenolic compound that scavenges free radicals and exerts anti-inflammatory effects. Forkhead box O3a (FOXO3a), a transcription factor that plays important roles in aging processes, decreases with age and is negatively regulated through phosphorylation by phosphatidylinositol 3-kinase (PI3K)/Akt signaling. The present study investigated the efficacy of short-term ferulate feeding on age-related changes in PI3K/Akt/FOXO3a and upstream insulin signaling pathways in aged rats. In addition, changes in manganese superoxide dismutase (MnSOD) and catalase expression were examined because of their dependence on PI3K/Akt/FOXO3a activity. Short-term feeding experiments were done with a diet containing ferulate that was given to aged rats at doses of 3 or 6 mg kg −1 day −1 for 10 days.Results showed that FOXO3a activity was increased in the ferulate-fed old group compared with the control old group. Also, ferulate suppressed the PI3K/Akt signaling pathway that is responsible for FOXO3a inhibition in aged rats. Plasma insulin levels and the upstream insulin signaling pathway were also modulated by ferulate correspondingly with PI3K/ Akt/FOXO3a activity. The age-related decrease in two major antioxidant enzymes, MnSOD and catalase, was blunted by ferulate, which was accompanied by FOXO3a transcriptional activity. The significance of the present study is the finding that short-term feeding of ferulate effectively modulates age-related renal FOXO3a, PI3K/Akt and insulin signaling pathways, and MnSOD and catalase expression, all of which may be beneficial for attenuating the aging process.

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Section: Effect Of Ferulate On Insulin Signaling and Plasma Insulin Lsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 94%

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Choi

Kim

Lee

et al. 2011

AGE

Self Cite

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“…2). Once again while aged kidneys exhibit upregulated levels of phosphorylated FoxO (Kim et al 2008), highly differentiated CD4 + T cells display low levels of phosphorylated FoxO, but rather than being protective, these cells are more prone to apoptosis (Riou et al 2007). (Morales et al 2010).…”

Section: Molecular Mediators Of Age-related Inflammationmentioning

confidence: 99%

The role of the T cell in age-related inflammation

Macaulay

Akbar

Henson

2012

AGE

105

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Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is highlighted by their being predictors of earlier mortality. We have recently published that the proinflammatory cytokine TNFα is a strong inducer of CD4 + T-cell senescence and T-cell differentiation, adding to the growing body of literature implicating proinflammatory molecules in mediating these critical age-related T-cell alterations. Moreover, the inflammatory process is also being increasingly implicated in the pathogenesis of many common and severe age-related diseases, including cancer, cardiovascular diseases and type 2 diabetes. Furthermore, major age-related risk factors for poor health, such as obesity, stress and smoking, are also associated with an upregulation in systemic inflammatory markers. We propose the idea that the ensuing inflammatory response to influenza infection propagates cardiovascular diseases and constitutes a major cause of influenzarelated mortality. While inflammation is not a negative phenomenon per se, this age-related dysregulation of inflammatory responses may play crucial roles driving age-related pathologies, T-cell immunosenescence and CMV reactivation, thereby underpinning key features of the ageing process.

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“…Table 1 summaries some of the most important signaling molecules involved in CR-induced biological and physiological responses. FOXO ↓ [89,97] GSK-3β ↓ [93,98] HIF-1 ↓ [95,99] HSF-1 ↑ [94] HSP-70 ↑ [94,100] mTOR ↓ [90,101] NF-κB ↓ [81,82,95,97] PGC-1α ↑ [91,92] PPAR α ↑ [91,102] SIRT1 ↑↓ [92,93,103] ↑=increase in signal transduction; ↓=decrease in signal transduction.…”

Section: Signal Transduction Mechanism Involved In Crmentioning

confidence: 99%

Caloric restriction and heart function: is there a sensible link?

Han

Ren

2010

Acta Pharmacol Sin

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Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. In general, the daily caloric intake subjected to CR has been restricted to 50% to 70% of the average food intake in subjects eating ad libitum [1,2] . CR was first reported to retard aging and prolong median and maximal life span in the 1930s [3] . Over the last several decades, CR has been widely studied which exhibits an apparent beneficial impact on longevity, ageassociated diseases, and attenuation of functional decline, across a broad variety of species (including rats, mice, fish, flies, worms and yeast) [4,5] . Moreover, CR provides protection against a cadre of chronic diseases including diabetes mellitus, neurodegenerative diseases, autoimmune disorders [6][7][8] and cancer [9][10][11][12] . CR has been shown to alter a variety of physiological parameters especially reduced metabolic rate and oxidative damage, resulting in a decrease in the incidence of cardiovascular diseases [13] . In response to energy deficiency, experimental animals experience a drastic decrease in both fat mass and lean body mass. Muscle mass is overtly reduced, although the rate of loss of function and mass/body weight with the aging process is attenuated [9,[14][15][16] . Metabolic rate may decrease transiently although studies have indicated similar metabolic rate per kg lean body mass to that of ad libitum fed rodents in longterm CR protocol [17] . Body temperature, systolic and diastolic blood pressure all decrease [18,19] along with the reduced sympathetic activity [20] . CR-treated animals are more spontaneously active and display superior cognitive abilities compared to their ad libitum counterparts [21,22] .The most prominent mechanism that may be responsible for the beneficial health and physiological effects of CR are usually mediated through increased insulin sensitivity which results in reduced plasma glucose and insulin concentrations and improved glucose tolerance [23] ; reduced levels of oxidative stress (decreased oxidative damage to proteins, lipids and DNA) [24] , increased resistance to various types of stress including heat, oxidative and metabolic stress [25] as well as enhanced immune function [26] . Impact of CR on agingAn inverse relationship between calorie intake and lifespan has been revealed in mice, suggesting a key role for regulators of energy metabolism in the mechanism of CR. Accordingly, CR-induced metabolic reprogramming may be a key event in the mechanism of lifespan extension [27,28] . The age when CR is started, the severity of restriction, and strain or genetic background of animals determine the magnitude of life extension. The only mammals in which CR has clearly been shown ReviewCaloric restriction and heart function: is there a sensible link? Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. Ample of clinical and experimental evidence has demonstrated that CR is capable of retarding aging p...

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The activation of NF-κB through Akt-induced FOXO1 phosphorylation during aging and its modulation by calorie restriction

Cited by 102 publications

References 38 publications

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

The role of the T cell in age-related inflammation

Caloric restriction and heart function: is there a sensible link?

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