The life‐extending effect of dietary restriction requires
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            oxo3 in mice

Shimokawa, Isao; Komatsu, Toshimitsu; Hayashi, Nobutaka; Kim, Sang Eun; Kawata, Takuya; Park, Seong Joon; Hayashi, Hiroko; Yamaza, Haruyoshi; Chiba, Takuya; Mori, Ryoichi

doi:10.1111/acel.12340

Cited by 98 publications

(86 citation statements)

References 10 publications

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“…There is no doubt that in the near future experiments will shed light on this central aspect of FOXO biology. Intriguingly, recent studies show that the life‐extending effect of dietary restriction requires Foxo3 but not Foxo1 in mice (Yamaza et al ., 2010; Shimokawa et al ., 2015). The mechanism(s) by which Foxo factors contribute to lifespan remain elusive.…”

Section: Animal Modelsmentioning

confidence: 99%

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

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SummaryAging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.

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Section: Animal Modelsmentioning

confidence: 99%

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

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“…Like DAF-16 in C. elegans, FoxO transcription factors together with calorie restriction and insulin signaling have been reported to regulate lifespan in rodents (Mulvey et al, 2014;Shimokawa et al, 2015). For example, decreased insulin signaling correlates with human longevity (Kojima et al, 2004;Pawlikowska et al, 2009), as do several genetic variants in FOXO3 (Willcox et al, 2008;Pawlikowska et al, 2009;Flachsbart et al, 2009;Li et al, 2009).…”

Section: Foxo In Mammalian Longevitymentioning

confidence: 99%

“…For example, decreased insulin signaling correlates with human longevity (Kojima et al, 2004;Pawlikowska et al, 2009), as do several genetic variants in FOXO3 (Willcox et al, 2008;Pawlikowska et al, 2009;Flachsbart et al, 2009;Li et al, 2009). In mice, FoxO3, but not FoxO1, is required for an expanded lifespan due to calorie restriction (Shimokawa et al, 2015). However, a meta analysis calls this conclusion for calorie restriction into question (Swindell, 2012).…”

Section: Foxo In Mammalian Longevitymentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

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Forkhead box (Fox) transcription factors are evolutionarily conserved in organisms ranging from yeast to humans. They regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In many cases, the absence of even a single Fox transcription factor is lethal. In this Primer, we provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development.

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“…Dietary restriction (DR) can extend lifespan in numerous species, including mammals, and prevent age‐related impairment in organ function, including kidney dysfunction (Colman et al., 2014; Kume et al., 2010; Lin, Ford, Haigis, Liszt, & Guarente, 2004; Shimokawa et al., 2015). In contrast, DR has only one principal negative effect: muscle weakness due to protein wasting (Lopes, Russell, Whitwell, & Jeejeebhoy, 1982; Thomas, 2007), which also represents a health problem in both elderly subjects and patients with kidney disease (Goodpaster et al., 2006; Workeneh & Mitch, 2010).…”

Section: Introductionmentioning

confidence: 99%

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

et al. 2018

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SummaryExtending healthy lifespan is an emerging issue in an aging society. This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)‐induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age‐related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA. Simple DR prevented the age‐dependent decrease in slow‐twitch muscle fiber function but reduced absolute fast‐twitch muscle fiber function. DR‐induced fast‐twitch muscle fiber dysfunction was improved by recovering either dietary NEAAs or EAAs. In the ad libitum‐fed and the DR plus EAA groups, the renal content of methionine, an EAA, was significantly higher, accompanied by lower renal production of hydrogen sulfide (H2S), an endogenous antioxidant. Finally, removal of methionine from the dietary EAA supplement diminished the adverse effects of dietary EAA on lifespan and kidney injury in the diet‐restricted aged mice, which were accompanied by a recovery in H2S production capacity and lower oxidative stress. These data imply that a dietary approach could combat kidney aging and prolong lifespan, while preventing muscle weakness, and suggest that renal methionine metabolism and the trans‐sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.

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The life‐extending effect of dietary restriction requires F oxo3 in mice

Cited by 98 publications

References 10 publications

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Fox transcription factors: from development to disease

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

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