Lifespan extension by conditions that inhibit translation in <i>Caenorhabditis elegans</i>

Hansen, Malene; Taubert, Stefan; Crawford, Douglas K.; Libina, Nataliya; Lee, Seung-Jae; Kenyon, Cynthia

doi:10.1111/j.1474-9726.2006.00267.x

Cited by 833 publications

(952 citation statements)

References 52 publications

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“…In C. elegans studies, reducing the levels of key proteins involved in translation, such as ribosomal proteins, ribosomal‐protein S6 kinase, and translation initiation factors, increased the lifespan of C. elegans (Hansen et al ., 2007; Pan et al ., 2007). Ribosomal‐protein S6 kinase also regulates lifespan in mammalian models (Selman et al ., 2009).…”

Section: Discussionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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Section: Discussionmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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“…Inhibition of mTORC1 and its downstream effector S6K does not require FOXO (Hansen et al., 2007; Pan et al., 2007) while rapamycin‐induced longevity depends on FOXO (Robida‐Stubbs et al., 2012). These studies support the notion that mTORC1 regulates aging by mechanisms that both overlap and distinct from FOXO.…”

Section: Discussionmentioning

confidence: 99%

FOXO protects against age‐progressive axonal degeneration

Hwang

Santo

et al. 2017

Aging Cell

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SummaryNeurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself.

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“…Diverse approaches including different dietary regimens or using compounds that mimic dietary restriction have been employed to investigate the effect of dietary restriction on lifespan extension in C. elegans (Kenyon, 2010b). Chronic food limitation increases lifespan by downregulating TOR activity, which increases autophagy and diminishes translation, probably through PHA‐4/FOXA transcription factor and S6 kinase, respectively, in a DAF‐16/FoxO‐independent manner (Kaeberlein et al ., 2005; Hansen et al ., 2007; Pan et al ., 2007; Sheaffer et al ., 2008). AMPK (AMP kinase), an energy sensor for cellular AMP/ATP ratio that enables catabolic reactions for energy gain, has been shown to respond to dietary restriction by increasing stress resistance and extending longevity in C. elegans in a DAF‐16/FOXO‐dependent manner (Apfeld et al ., 2004; Greer et al ., 2007a).…”

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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Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans

Cited by 833 publications

References 52 publications

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

FOXO protects against age‐progressive axonal degeneration

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

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