Neopterin extends lifespan in an ATFS-1-dependent manner.

Neopterin, a byproduct of tetrahydrobiopterin synthesis, is commonly used as a biomarker for immune system activation. In addition to its role in immune responses, neopterin levels are known to increase with age. Its impact on longevity, however, remains unclear.

Anesthetic-like effects of ketamine in C. elegans.

Transparency of Caenorhabditis elegans enables microscopic in vivo imaging of cellular processes, but immobilization is required due to high locomotor activity. Here, anesthetic-like effects of dissociate anesthetic ketamine in adult C. elegans are presented using video recordings and infrared-based automated activity tracking.

Milk Fat Globule Membrane-Containing Protein Powder Promotes Fitness in .

Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilized to elucidate how MFGM-containing protein powder (MProPow), previously used in a clinical trial, affect the physiology of this model organism.

Loss of the histone chaperone UNC-85/ASF1 inhibits the epigenome-mediated longevity and modulates the activity of one-carbon metabolism.

Histone H3/H4 chaperone anti-silencing function 1 (ASF1) is a conserved factor mediating nucleosomal assembly and disassembly, playing crucial roles in processes such as replication, transcription, and DNA repair. Nevertheless, its involvement in aging has remained unclear. Here, we utilized the model organism Caenorhabditis elegans to demonstrate that the loss of UNC-85, the homolog of ASF1, leads to a shortened lifespan in a multicellular organism.

Folate receptor overexpression induces toxicity in a diet-dependent manner in C. elegans.

Folate receptor (FR) alpha (FOLR1) and beta (FOLR2) are membrane-anchored folate transporters that are expressed at low levels in normal tissues, while their expression is strongly increased in several cancers. Intriguingly, although the function of these receptors in, for example, development and cancer has been studied intensively, their role in aging is still unknown. To address this, we utilized Caenorhabditis elegans, in which FOLR-1 is the sole ortholog of folate receptors.

Tissue-specific effects of temperature on proteasome function.

Variation in ambient growth temperature can cause changes in normal animal physiology and cellular functions such as control of protein homeostasis. A key mechanism for maintaining proteostasis is the selective degradation of polyubiquitinated proteins, mediated by the ubiquitin-proteasome system (UPS). It is still largely unsolved how temperature changes affect the UPS at the organismal level.

Expanded CUG Repeats Trigger Disease Phenotype and Expression Changes through the RNAi Machinery in C. elegans.

Myotonic dystrophy type 1 is an autosomal-dominant inherited disorder caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. The RNAs bearing these expanded repeats have a range of toxic effects. Here we provide evidence from a Caenorhabditis elegans myotonic dystrophy type 1 model that the RNA interference (RNAi) machinery plays a key role in causing RNA toxicity and disease phenotypes.

De novo NAD synthesis enhances mitochondrial function and improves health.

Nicotinamide adenine dinucleotide (NAD) is a co-substrate for several enzymes, including the sirtuin family of NAD-dependent protein deacylases. Beneficial effects of increased NAD levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD synthesis pathway, controls cellular NAD levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse.

The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress.

Age-associated changes in chromatin structure have a major impact on organismal longevity. Despite being a central part of the ageing process, the organismal responses to the changes in chromatin organization remain unclear. Here we show that moderate disturbance of histone balance during C.

Mitochondria and Epigenetics - Crosstalk in Homeostasis and Stress.

Through epigenetic mechanisms cells integrate environmental stimuli to fine-tune gene expression levels. Mitochondrial function is essential to provide the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, which in turn can regulate the expression of mitochondrial proteins. In this review we summarize the function of mitochondria in the regulation of epigenetic mechanisms as a new aspect of mitonuclear communication.

Fluorescent Tools for In Vivo Studies on the Ubiquitin-Proteasome System.

The ubiquitin-proteasome system (UPS) plays a key role in maintaining proteostasis by degrading most of the cellular proteins. Traditionally, UPS activity is studied in vitro, in yeast, or in mammalian cell cultures by using short-lived GFP-based UPS reporters. Here, we present protocols for two fluorescent tools facilitating real-time imaging of UPS activity in living animals.

Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity.

Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C.

Suppression of RNAi by dsRNA-degrading RNaseIII enzymes of viruses in animals and plants.

Certain RNA and DNA viruses that infect plants, insects, fish or poikilothermic animals encode Class 1 RNaseIII endoribonuclease-like proteins. dsRNA-specific endoribonuclease activity of the RNaseIII of rock bream iridovirus infecting fish and Sweet potato chlorotic stunt crinivirus (SPCSV) infecting plants has been shown. Suppression of the host antiviral RNA interference (RNAi) pathway has been documented with the RNaseIII of SPCSV and Heliothis virescens ascovirus infecting insects.

Insulin/IGF-1 signaling regulates proteasome activity through the deubiquitinating enzyme UBH-4.

The proteasome plays an important role in proteostasis by carrying out controlled protein degradation in the cell. Impairments in proteasome function are associated with severe and often age-related diseases. Here, we have characterized a molecular mechanism linking insulin/IGF-1 signaling (IIS) to proteasome activity.

Proteasome activity influences UV-mediated subnuclear localization changes of NPM.

UV damage activates cellular stress signaling pathways, causes DNA helix distortions and inhibits transcription by RNA polymerases I and II. In particular, the nucleolus, which is the site of RNA polymerase I transcription and ribosome biogenesis, disintegrates following UV damage. The disintegration is characterized by reorganization of the subnucleolar structures and change of localization of many nucleolar proteins.

Specific SKN-1/Nrf stress responses to perturbations in translation elongation and proteasome activity.

SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules, a SKN-1/Nrf function that is both well-known and conserved. Here we show that SKN-1 has a broader and more complex role in maintaining cellular stress defenses.

A photoconvertible reporter of the ubiquitin-proteasome system in vivo.

The ubiquitin-proteasome system (UPS) orchestrates many cellular and tissue-specific processes by degrading damaged and key regulatory proteins. To enable investigation of UPS activity in different cell types in a living animal, we developed a photoconvertible fluorescent UPS reporter system for live imaging and quantification of protein degradation in Caenorhabditis elegans. Our reporter consists of the photoconvertible fluorescent protein Dendra2 targeted for proteasomal degradation by fusion to the UbG76V mutant form of ubiquitin.