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  • High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan

    Highlights Mapped lifespan determinants in a C. elegans GRP using multiomics data Validated three longevity modulators, comprising rict-1, gfm-1, and mltn-1 GFM1 variants linked to age-related heart failure in UK Biobank data Summary Lifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits…

    January 22, 2025
  • A robotic platform for fully automated ageing studies in C. elegans

    C. elegans is a powerful model organism for ageing studies. However, the traditional protocols, which continue to be broadly used, rely on manual handling, making them labor-intensive and time-consuming. Automation of these processes would greatly benefit long-term studies of C. elegans. Significant progress has been achieved over the past decade in the techniques to study…

    June 26, 2023
  • Fully automated laboratory device for aging studies using the nematode Caenorhabditis elegans.

    Here we describe an innovative microfluidic platform using the nematode Caenorhabditis elegans, as an ideal model organism for the study of aging due to its short lifespan and tractable genetics. Our platform allows full automation of the entire process of culture, treatment, imaging and analysis of C. elegans, at unprecedented levels of throughput and standardization. The…

    March 13, 2023
  • Mitonuclear protein imbalance as a conserved longevity mechanism.

    Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity regulators. MRP knockdown triggers mitonuclear protein imbalance, reducing mitochondrial respiration and activating the mitochondrial unfolded protein response.…

    March 13, 2023
  • An evolutionarily conserved role for the aryl hydrocarbon receptor in the regulation of movement.

    The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some of these variants have been established with effects on general metabolic phenotypes such as glucose response and bone strength. Here we phenotype…

    March 13, 2023
  • NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

    Making muscle work better Degenerating muscle—whether from muscular dystrophies, myopathies, or other diseases—loses its mitochondria (the energy supply) and an essential cofactor nicotinamide adenine dinucleotide (NAD+), while gaining an extra load of enzymes that use up NAD+, as reported by Ryu and colleagues. The resulting loss of NAD+ is exacerbated by a drop in NAD+…

    March 13, 2023
  • An in vivo microfluidic study of bacterial transit in C. elegans nematodes.

    Caenorhabditis elegans (C. elegans) constitutes an important model organism for use in nutrition and aging studies. We report a novel method for studying the dynamics of Escherichia coli (E. coli) bacterial transit through the worms’ intestine. A microfluidic chip was designed for alternating C. elegans on-chip culture and immobilization, thereby enabling periodic high-resolution time-lapse imaging…

    March 13, 2023
  • The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling.

    NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological restoration of NAD(+) prevents age-associated metabolic decline and promotes longevity…

    March 13, 2023
  • NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.

    Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation…

    March 13, 2023
  • Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle.

    We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial function remains to be explored. Here, we show tight negative correlation between Parp-1 expression and energy expenditure in heterogeneous mouse populations, indicating that variations in…

    March 13, 2023
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