Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease

Hesp, Kylie; Smant, G.; Kammenga, J.E.

doi:10.1016/j.exger.2015.09.006

Cited by 74 publications

(51 citation statements)

References 67 publications

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“…FOXO ensures the survival of maximal numbers of naïve T cells33, modulates helper T-cell quiescence34, and prevents inflammation-induced apoptosis of neutrophils35 that contributes to intestinal resistance against infection and preservation of the microbiota58. FOXO plays a key role in T-cell homeostasis and regulation of inflammation and immunity596061. The observation that SYR50 increased the nuclear localization of FOXO3 in Treg cells (Fig.…”

Section: Discussionmentioning

confidence: 98%

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

Cho

Kim

Lee

et al. 2016

Sci Rep

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Age-associated immunological dysfunction (immunosenescence) is closely linked to perturbation of the gut microbiota. Here, we investigated whether syringaresinol (SYR), a polyphenolic lignan, modulates immune aging and the gut microbiota associated with this effect in middle-aged mice. Compared with age-matched control mice, SYR treatment delayed immunosenescence by enhancing the numbers of total CD3+ T cells and naïve T cells. SYR treatment induced the expression of Bim as well as activation of FOXO3 in Foxp3+ regulatory T cells (Tregs). Furthermore, SYR treatment significantly enhanced the Firmicutes/Bacteroidetes ratio compared with that in age-matched controls by increasing beneficial bacteria, Lactobacillus and Bifidobacterium, while reducing the opportunistic pathogenic genus, Akkermansia. In addition, SYR treatment reduced the serum level of lipopolysaccharide-binding protein, an inflammatory marker, and enhanced humoral immunity against influenza vaccination to the level of young control mice. Taken together, these findings suggest that SYR may rejuvenate the immune system through modulation of gut integrity and microbiota diversity as well as composition in middle-aged mice, which may delay the immunosenescence associated with aging.

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Section: Discussionmentioning

confidence: 98%

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

Cho

Kim

Lee

et al. 2016

Sci Rep

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“…IIS defines various cellular processes, including innate immunity and stress response. Reduced insulin signaling extends lifespan and improves proteotoxic stress resistance via the activation of multiple transcription factors (Cohen et al., 2010, Hesp et al., 2015, Kenyon, 2010, Kevei and Hoppe, 2014). DAF-2 has been identified as a membrane bound receptor regulating the IIS pathway in Caenorhabditis elegans .…”

Section: Introductionmentioning

confidence: 99%

The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover

Tawo

Pokrzywa

Kevei

et al. 2017

Cell

117

149

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SummaryAging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging. INSR is a direct target of CHIP, which triggers receptor monoubiquitylation and endocytic-lysosomal turnover to promote longevity. However, upon proteotoxic stress conditions and during aging, CHIP is recruited toward disposal of misfolded proteins, reducing its capacity to degrade the INSR. Our study indicates a competitive relationship between proteostasis and longevity regulation through CHIP-assisted proteolysis, providing a mechanistic concept for understanding the impact of proteome imbalance on aging.

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“…In ageing, the decrease in telomere length, which is important in the control of longevity, is a result of the combined effects of oxidative stress and repeated cell replications [5]. FOXO transcription factors, which play important roles in the signal transduction pathway associated with stress and aging phenotypes, are also strongly regulated by oxidative stress [6]. In major demyelinating and non-demyelinating neurodegenerative diseases including Multiple Sclerosis (MS), X-linked adrenoleukodystrophy (X-ALD), Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, oxidative stress is thought to contribute to neuronal loss and axonal damage, which are considered key elements in the onset and progression of these diseases [7].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

Debbabi

Nury

Zarrouk

et al. 2016

IJMS

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Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

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Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease

Cited by 74 publications

References 67 publications

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

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