Rapid in vivo screening of interventions targeting metabolic health and weight management. Nutraceutical developers need faster in vivo evidence to prioritize ingredients for metabolic health, weight management, and resilience under nutrient excess before committing to slower and more expensive mammalian studies. Here, we propose a high-glucose C. elegans assay to tackle this industry and health…
The discovery of RNA interference (RNAi) in C. elegans transformed how we study and manipulate genes. Today, this same mechanism that was once a curiosity of basic biology is the foundation of life-saving RNA therapeutics like Onpattro® and Venclexta®. In C. elegans, RNAi can spread systemically, silencing genes throughout the whole organism, and it can…
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…
Mitochondrial dysfunction is at the core of many diseases ranging from inherited metabolic diseases to common conditions that are associated with aging. Although associations between aging and mitochondrial function have been identified using mammalian models, much of the mechanistic insight has emerged from Caenorhabditis elegans. Mitochondrial respiration is recognized as an indicator of mitochondrial health.…
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…
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…
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…
Mitochondria are semi-autonomous organelles regulated by a complex network of proteins that are vital for many cellular functions. Because mitochondrial modulators can impact many aspects of cellular homeostasis, their identification and validation has proven challenging. It requires the measurement of multiple parameters in parallel to understand the exact nature of the changes induced by such…