3 research outputs found
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High-throughput small molecule screening reveals Nrf2-dependent and -independent pathways of cellular stress resistance.
Aging is the dominant risk factor for most chronic diseases. Development of antiaging interventions offers the promise of preventing many such illnesses simultaneously. Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that induced resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS). Some rescue compounds conferred resistance to a single stressor, while others provoked multiplex resistance. Induction of stress resistance in fibroblasts was predictive of longevity extension in a published large-scale longevity screen in Caenorhabditis elegans, although not in testing performed in worms and flies with a more restricted set of compounds. Transcriptomic analysis and genetic studies implicated Nrf2/SKN-1 signaling in stress resistance provided by two protective compounds, cardamonin and AEG 3482. Small molecules identified in this work may represent attractive tools to elucidate mechanisms of stress resistance in mammalian cells
Recommended from our members
High-throughput small molecule screening reveals Nrf2-dependent and -independent pathways of cellular stress resistance
Aging is the dominant risk factor for most chronic diseases. Development of antiaging interventions offers the promise of preventing many such illnesses simultaneously. Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that induced resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS). Some rescue compounds conferred resistance to a single stressor, while others provoked multiplex resistance. Induction of stress resistance in fibroblasts was predictive of longevity extension in a published large-scale longevity screen in
, although not in testing performed in worms and flies with a more restricted set of compounds. Transcriptomic analysis and genetic studies implicated Nrf2/SKN-1 signaling in stress resistance provided by two protective compounds, cardamonin and AEG 3482. Small molecules identified in this work may represent attractive tools to elucidate mechanisms of stress resistance in mammalian cells
A transomic cohort as a reference point for promoting a healthy human gut microbiome
More than a decade of gut microbiome studies have a common goal of improving human health. However, while most of the disease studies have focused on the elderly or the middle-aged, a reference cohort for the gut microbiome in young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here, we present a cohort including 2183 adults with high-depth metagenomic shotgun sequencing data for the fecal microbiome and other omics data. In this multiomic cohort, we observe a number of vitamins, hormones, amino acids, and trace elements that correlated with the gut microbiome. Many of the associations are validated in an additional cohort consisting of 1404 individuals. Our comprehensive data are poised to provide advice to future populations and mechanistic study designs to better understand and manage our gut microbiome