Serotonin deficiency from constitutive SKN-1 activation drives pathogen apathy.

Unlabelled: When an organism encounters a pathogen, the host innate immune system activates to defend against pathogen colonization and toxic xenobiotics produced. employ multiple defense systems to ensure survival when exposed to including activation of the cytoprotective transcription factor SKN-1/NRF2. Although wildtype quickly learn to avoid pathogens, here we describe a peculiar apathy-like behavior towards PA14 in animals with constitutive activation of SKN-1, whereby animals choose not to leave and continue to feed on the pathogen even when a non-pathogenic and healthspan-promoting food option is available.

Rapid Lipid Quantification in by Oil Red O and Nile Red Staining.

The ability to stain lipid stores allows for the facile assessment of metabolic status in individuals of a population following genetic and environmental manipulation or pharmacological treatment. In the animal model , lipids are stored in and mobilized from intracellular lipid droplets in the intestinal and hypodermal tissues. The abundance, size, and distribution of these lipids can be readily assessed by two staining methods for neutral lipids: Oil Red O (ORO) and Nile Red (NR).

Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects.

Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC®Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics.

Metabolic Assessment of Lipid Abundance and Distribution.

Lipids are an essential macromolecule used for diverse functions including use for structural components of membranes, energy storage, and signaling molecules. The regulation of cellular lipid stores is critical for maintaining organismal metabolic homeostasis. Lipid homeostasis can decline with age, which can lead to poor health outcomes and accelerate the progression of disease states.

Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

Early host responses toward pathogens are essential for defense against infection. In , the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan.

Programmed DNA Breaks Activate the Germline Genome in Caenorhabditis elegans.

In Caenorhabditis elegans, the primordial germ cells Z2 and Z3 are born during early embryogenesis and then held in a transcriptionally quiescent state where the genome is highly compacted. When hatched L1s feed, the germline genome decompacts, and RNAPII is abruptly and globally activated. A previously documented yet unexplained feature of germline genome activation in the worm is the appearance of numerous DNA breaks coincident with RNAPII transcription.