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The nematode C. elegans has long served as a gold‐standard model organism in aging research, particularly since the discovery of long‐lived mutants in conserved aging pathways including daf‐2 (IGF1) and age‐1 (PI3K). Its short lifespan and small size make it highly suitable for high‐throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects, especially those related to drug‐bacteria interactions, remain a contentious issue in the literature. In this study, we evaluated 16 of the most frequently reported lifespan‐extending molecules in C. elegans, examining their effects on lifespan with two different diets (live and UV‐killed OP50). In addition, we assessed the compounds' impact on bacterial growth, their effects on various nematode strains, and the impact of the starting age of treatment. Our findings first confirmed robust lifespan extension by many, but not all, of the 16 tested compounds from the literature, and revealed that some of them could be combined to obtain additive effects. Additionally, we showed that some of these compounds also extend lifespan in the fly D. melanogaster, demonstrating a conserved effect across species. Finally, by expanding our screen to a broader pool of molecules, we identified novel lifespan‐extending compounds in C. elegans. We evaluated 16 of the most frequently reported lifespan‐extending molecules in C. elegans, examining their effects on lifespan with live and UV‐killed OP50. We assessed the compounds' impact on bacterial growth, and their effects on various nematode strains. We confirmed robust lifespan extension by many, but not all, of the 16 tested compounds, and revealed some potential for combinatorial additive effects. Lastly, by expanding our screen to a broader pool of molecules, we identified novel lifespan‐extending compounds in C. elegans.

The dynamicity of the mitochondrial network is crucial for meeting the ever‐changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected, and well‐organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age‐associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp‐1 or the mitochondrial fusion genes fzo‐1 and eat‐3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance, and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which in the case of the mitochondrial fusion overexpression strains appears to be at least partially due to the upregulation of multiple pathways of cellular resilience in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity. Overexpression of mitochondrial fission genes or mitochondrial fusion genes both result in mitochondrial fragmentation, increased resilience, and extended longevity. Overexpression of mitochondrial fusion genes activates multiple pathways of cellular resilience, some of which are required for their extended longevity. Altering the levels of mitochondrial fission or fusion genes can activate a stress response that promotes longevity.

The microbiota is a key determinant of the physiology and immunity of animal hosts. The factors governing the transmissibility of viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans and represent an integral part of the natural environment of C. elegans . We determined the effects of bacteria isolated with C. elegans from its natural environment on the transmission of Orsay virus in C. elegans using quantitative virus transmission and host susceptibility assays. We observed that Ochrobactrum species promoted Orsay virus transmission, whereas Pseudomonas lurida MYb11 attenuated virus transmission relative to the standard laboratory bacterial food Escherichia coli OP50. We found that pathogenic Pseudomonas aeruginosa strains PA01 and PA14 further attenuated virus transmission. We determined that the amount of Orsay virus required to infect 50% of a C. elegans population on P. lurida MYb11 compared with Ochrobactrum vermis MYb71 was dramatically increased, over three orders of magnitude. Host susceptibility was attenuated even further in the presence of P. aeruginosa PA14. Genetic analysis of the determinants of P. aeruginosa required for attenuation of C. elegans susceptibility to Orsay virus infection revealed a role for regulators of quorum sensing. Our data suggest that distinct constituents of the C. elegans microbiota and potential pathogens can have widely divergent effects on Orsay virus transmission, such that associated bacteria can effectively determine host susceptibility versus resistance to viral infection. Our study provides quantitative evidence for a critical role for tripartite host-virus-bacteria interactions in determining the transmissibility of viruses among susceptible hosts.

Embryogenesis is the most basic process in developmental biology. Effectively and simply quantifying cell shape is challenging for the complex and dynamic 3D embryonic cells. Traditional descriptors such as volume, surface area, and mean curvature often fall short, providing only a global view and lacking in local detail and reconstruction capability. Addressing this, we introduce an effective integrated method, 3D Cell Shape Quantification (3DCSQ), for transforming digitized 3D cell shapes into analytical feature vectors, named eigengrid ( proposed grid descriptor like eigen value), eigenharmonic, and eigenspectrum. We uniquely combine spherical grids, spherical harmonics, and principal component analysis for cell shape quantification. We demonstrate 3DCSQ’s effectiveness in recognizing cellular morphological phenotypes and clustering cells. Applied to Caenorhabditis elegans embryos of 29 living embryos from 4- to 350-cell stages, 3DCSQ identifies and quantifies biologically reproducible cellular patterns including distinct skin cell deformations. We also provide automatically cell shape lineaging analysis program. This method not only systematizes cell shape description and evaluation but also monitors cell differentiation through shape changes, presenting an advancement in biological imaging and analysis.

The antioxidant effect of probiotics has been widely recognized across the world, which is of great significance in food, medicine, and aquaculture. There are abundant marine microbial resources in the ocean, which provide a new space for humans to explore new probiotics. Previously, we reported on the anti-infective effects of Planococcus maritimu ML1206, a potential marine probiotic. The antioxidant activity of ML1206 in C. elegans was studied in this paper. The study showed that ML1206 could improve the ability of nematodes to resist oxidative stress and effectively prolong their lifespan. The results confirmed that ML1206 could significantly increase the activities of CAT and GSH-PX, and reduce the accumulation of reactive oxygen species (ROS) in nematodes under oxidative stress conditions. In addition, ML1206 promoted DAF-16 transfer to the nucleus and upregulated the expression of sod-3, hsp-16.2, and ctl-2, which are downstream antioxidant-related genes of DAF-16. Furthermore, the expression of the SOD-3::GFP and HSP-16.2::GFP was significantly higher in the transgenic strains fed with ML1206 than that in the control group fed with OP50, with or without stress. In summary, these findings suggest that ML1206 is a novel marine probiotic with an antioxidant function that stimulates nematodes to improve their defense abilities against oxidative stress and prolong the lifespan by regulating the translocation of FOXO/DAF-16. Therefore, ML1206 may be explored as a potential dietary supplement in aquaculture and for anti-aging and antioxidant purposes.

Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age‐related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S‐transferases, induced by the transcription factor skinhead‐1 (SKN‐1). Notably, VA upregulated the transcript levels of skn‐1 or its mammalian ortholog NRF2 in both C. elegans, human cells, and liver tissues of mice. Moreover, the loss‐of‐function genetic models demonstrated a critical involvement of the SKN‐1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti‐aging and anti‐oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age‐related disorders. Vitamin A improves stress resistance and extends longevity in C. elegans. SKN‐1 transcription factor is critical for these effects of vitamin A.

Summary Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD+‐dependent deacylases known as sirtuins, and increases in NAD+ that derive from higher levels of respiration. Here, we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens [DAF‐16 (FOXO), SKN‐1 (Nrf1/2/3), PHA‐4 (FOXA), AAK‐2 (AMPK)]. Complete DR lifespan extension required the sirtuin SIR‐2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC‐1, a key NAD+ salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc‐1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD+‐dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD+ salvage. Under DR conditions, NAD+‐dependent processes may be supported by a DR‐induced shift toward oxidative metabolism rather than an increase in total respiration.

Background The first metazoan genome sequenced, that of Caenorhabditis elegans , has motivated animal genome evolution studies. To date > 50 species from the genus Caenorhabditis have been sequenced, allowing research on genome variation. Results In the present study, we describe a new gonochoristic species, Caenorhabditis niphades n. sp., previously referred as C. sp. 36, isolated from adult weevils ( Niphades variegatus ), with whom they appear to be tightly associated during its life cycle. Along with a species description, we sequenced the genome of C. niphades n. sp. and produced a chromosome-level assembly. A genome comparison highlighted that C. niphades n. sp. has the smallest genome (59 Mbp) so far sequenced in the Elegans supergroup, despite being closely related to a species with an exceptionally large genome, C. japonica . Conclusions The compact genome of C. niphades n. sp. can serve as a key resource for comparative evolutionary studies of genome and gene number expansions in Caenorhabditis species .

The transcription factor HSF‐1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF‐1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF‐1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF‐1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF‐1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild‐type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity‐related signaling pathways become induced upon HSF‐1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF‐1‐depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN‐1/Nrf2‐mediated oxidative stress response pathway, as well as an innate immunity‐related pathway, suggesting a mutual compensatory interaction between HSF‐1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF‐1 activity is manipulated in humans. Inactivating HSF‐1 (heat shock factor 1), the master regulator of heat shock response, paradoxically increases the thermotolerance of the nematode C. elegans in an age‐dependent manner. In the absence of a functional HSF‐1 distinct cellular stress response and immunity‐related signaling pathways become induced. The activity of the unfolded protein response of the endoplasmic reticulum and the SKN‐1/Nrf2‐mediated oxidative stress response pathway, as well as an innate immunity‐related pathway, are required for the increase in thermotolerance.

We have generated a single-copy knock-in loci for defined gene expression (SKI LODGE) system to insert any DNA by CRISPR/Cas9 at defined safe harbors in the Caenorhabditis elegans genome. Utilizing a single crRNA guide, which also acts as a Co-CRISPR enrichment marker, any DNA sequence can be introduced as a single copy, regulated by different tissue-specific promoters. The SKI LODGE system provides a fast, economical, and effective approach for generating single-copy ectopic transgenes in C. elegans.