A fat-promoting plant extract from Artemisia scoparia exerts geroprotective effects on C. elegans health & lifespan

Abstract Like other biological processes, aging is not random, but subject to molecular control. Natural products that act on conserved metabolic pathways may provide entry points to extend animal lifespan and promote healthy aging. Here, we show that a botanical extract from Artemisia scoparia (SCO), which promotes fat storage and metabolic resiliency in mice, exerts pro-longevity effects on the nematode Caenorhabditis elegans, even when administered in mid-adulthood. SCO-treated worms exhibit significantly higher levels of fat compared to controls but live up to 40% longer, with signs of improved stress resistance in late age. Molecularly, SCO links elevated fat to enhanced longevity and stress resistance via activation of the transcription factor DAF-16/FOXO and upregulation of DAF-16-targeted Δ9 desaturases, lifespan-extending metabolic enzymes that oversee the biosynthesis of monounsaturated fatty acids. These findings identify SCO as a natural product that can modify fat regulation for longevity benefit and add to growing evidence indicating that elevated fat can be pro-longevity in some circumstances.

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Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage

Biomolecules ◽

10.3390/biom10070993 ◽

2020 ◽

Vol 10 (7) ◽

pp. 993

Author(s):

Yuri Lee ◽

Hyeseon Jeong ◽

Kyung Hwan Park ◽

Kyung Won Kim

Keyword(s):

Caenorhabditis Elegans ◽

Therapeutic Strategy ◽

Axon Regeneration ◽

Neuronal Damage ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

C Elegans ◽

Neuronal Functions ◽

Molecular Components

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.

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Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules that Affect Aging Pathways and Extend C. elegans’ Lifespan

10.1101/735415 ◽

2019 ◽

Author(s):

Peichuan Zhang ◽

Yuying Zhai ◽

James Cregg ◽

Kenny Kean-Hooi Ang ◽

Michelle Arkin ◽

...

Keyword(s):

Small Molecules ◽

Cell Line ◽

Stress Resistance ◽

Fibroblast Cell ◽

Cellular Level ◽

Healthy Human ◽

Primary Fibroblast ◽

C Elegans ◽

Healthy Longevity ◽

Entry Points

AbstractIncreased resistance to environmental stress at the cellular level is correlated with the longevity of long-lived mutants and wild-animal species. Moreover, in experimental organisms, screens for increased stress resistance have yielded mutants that are long-lived. To find entry points for small molecules that might extend healthy longevity in humans, we screened ∼100,000 small molecules in a human primary-fibroblast cell line and identified a set that increased oxidative-stress resistance. Some of the hits fell into structurally-related chemical groups, suggesting that they may act on common targets. Two small molecules increased C. elegans’ stress resistance, and at least 9 extended their lifespan by ∼10-50%. Thus, screening for increased stress resistance in human cells can enrich for compounds with promising pro-longevity effects. Further characterization of these compounds, including a chalcone that promoted stress resistance independently of NRF2, may elucidate new ways to extend healthy human lifespan.

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Tubular lysosome induction couples animal starvation to healthy aging

10.1101/2021.10.28.466256 ◽

2021 ◽

Author(s):

Tatiana V Villalobos ◽

Bhaswati Ghosh ◽

Sanaa Alam ◽

Tyler J Butsch ◽

Brennan M Mercola ◽

...

Keyword(s):

Food Intake ◽

Old Age ◽

Dietary Restriction ◽

Healthy Aging ◽

Critical Event ◽

Lifespan Extension ◽

Nematode Caenorhabditis Elegans ◽

Mtor Inhibition ◽

C Elegans ◽

New Class

Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans, we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging.

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Temporal Requirements of SKN-1/NRF as a Regulator of Lifespan and Proteostasis in Caenorhabditis elegans

10.1101/2020.11.24.395707 ◽

2020 ◽

Author(s):

Danielle Grushko ◽

Amir Levine ◽

Hana Boocholez ◽

Ehud Cohen

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Caenorhabditis Elegans ◽

Stress Resistance ◽

Healthy Aging ◽

Early Adulthood ◽

Protein Homeostasis ◽

Heat Shock Factor 1 ◽

C Elegans ◽

Extended Lifespan

AbstractLowering the activity of the Insulin/IGF-1 Signaling (IIS) cascade results in elevated stress resistance, enhanced protein homeostasis (proteostasis) and extended lifespan of worms, flies and mice. In the nematode Caenorhabditis elegans (C. elegans), the longevity phenotype that stems from IIS reduction is entirely dependent upon the activities of a subset of transcription factors including the Forkhead factor DAF-16/FOXO (DAF-16), Heat Shock Factor-1 (HSF-1), SKiNhead/Nrf (SKN-1) and ParaQuat Methylviologen responsive (PQM-1). While DAF-16 determines lifespan exclusively during early adulthood and governs proteostasis in early adulthood and midlife, HSF-1 executes these functions foremost during development. Despite the central roles of SKN-1 as a regulator of lifespan and proteostasis, the temporal requirements of this transcription factor were unknown. Here we employed conditional knockdown techniques and discovered that in C. elegans, SKN-1 is primarily important for longevity and proteostasis during late larval development through early adulthood. Our findings indicate that events that occur during late larval developmental through early adulthood affect lifespan and proteostasis and suggest that subsequent to HSF-1, SKN-1 sets the conditions, partially overlapping temporally with DAF-16, that enable IIS reduction to promote longevity and proteostasis. Our findings raise the intriguing possibility that HSF-1, SKN-1 and DAF-16 function in a coordinated and sequential manner to promote healthy aging.

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Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes—Impact of Mitochondria

Nutrients ◽

10.3390/nu11081886 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1886 ◽

Cited By ~ 12

Author(s):

Benjamin Dilberger ◽

Maike Passon ◽

Heike Asseburg ◽

Carmina V. Silaidos ◽

Fabian Schmitt ◽

...

Keyword(s):

Heat Stress ◽

Mitochondrial Function ◽

Stress Resistance ◽

High Performance ◽

Healthy Aging ◽

Respiratory Chain Complexes ◽

Phenolic Metabolites ◽

Expression Levels ◽

C Elegans ◽

Heat Stress Resistance

(1) Background: Polyphenols (PP) play an important role in the prevention of non-communicable diseases and may contribute to healthy aging. To investigate the molecular and cellular aspects of PP metabolites on longevity with a focus on mitochondrial function, we applied a pre-fermented mixture of polyphenols (Rechtsregulat®, RR) to rodents and nematodes. (2) Methods: The lifespans of Navar Medical Research Institute (NMRI) mice and C. elegans were recorded. The heat-stress resistance (37 °C) of C. elegans N2 was measured using nucleic staining. Respiration and membrane potential (ΔΨm) were measured in isolated mitochondria. The energetic metabolites adenosine triphosphate (ATP), lactate, and pyruvate were determined in lysates. Expression levels of longevity related genes were determined using quantitative real time polymerase chain reaction (qRT-PCR). Phenolic compounds were identified using ultra high performance liquid chromatography-diode array detection-Iontrap-multiple stage mass spectrometry (UHPLC-DAD-Iontrap-MSn). (3) Results: Several phenolic metabolites including protocatechuic acid (PCA) were identified in RR. Feeding of mice with RR resulted in a significantly increased lifespan. Heat-stress resistance (RR *** p = 0.0006; PCA **** p < 0.0001), median lifespan (NMRI: RR ** p = 0.0035; C. elegans RR * p = 0.0279; PCA **** p < 0.0001), and activity of mitochondrial respiratory chain complexes (RR *−** p = 0.0237 − 0.0052; PCA * p = 0.019 − 0.0208) of C. elegans were significantly increased after incubation with RR (10%) or PCA (780 µM). PCA significantly improved nematodes ΔΨm (* p = 0.02058) and ATP levels (* p = 0.029). RR significantly up-regulated lactate levels, indicating enhanced glycolysis. The expression levels of longevity related genes daf-16, sir-2.1, and skn-1 were significantly upregulated after PCA, and partially after RR administration. (4) Conclusion: Phenolic metabolites such as PCA have the potential to enhance health and lifespan and mitochondrial function, and thus may contribute to healthy aging.

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Apoptosis and development

Essays in Biochemistry ◽

10.1042/bse0390011 ◽

2003 ◽

Vol 39 ◽

pp. 11-24 ◽

Cited By ~ 6

Author(s):

Justin V McCarthy

Keyword(s):

Drosophila Melanogaster ◽

Mammalian Cells ◽

Cell Number ◽

Model Organisms ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

Apoptotic Pathway ◽

Genetic Pathways ◽

Evolutionarily Conserved ◽

Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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Faculty Opinions recommendation of Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732336919.793541328 ◽

2018 ◽

Author(s):

Philip Burcham

Keyword(s):

Stress Resistance ◽

Signalling Pathway ◽

C Elegans

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Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

Biogerontology ◽

10.1007/s10522-021-09913-2 ◽

2021 ◽

Vol 22 (2) ◽

pp. 215-236

Author(s):

Nadine Saul ◽

Steffen Möller ◽

Francesca Cirulli ◽

Alessandra Berry ◽

Walter Luyten ◽

...

Keyword(s):

Healthy Aging ◽

Model Organism ◽

Research Field ◽

Aging Research ◽

Genetic Manipulations ◽

C Elegans ◽

Starting Point ◽

Health Related ◽

Phenotype Measurement ◽

Or Gene

AbstractSeveral biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

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Sperm Competition in the Absence of Fertilization in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/152.1.201 ◽

1999 ◽

Vol 152 (1) ◽

pp. 201-208 ◽

Cited By ~ 2

Author(s):

Andrew Singson ◽

Katherine L Hill ◽

Steven W L’Hernault

Keyword(s):

Caenorhabditis Elegans ◽

Sperm Competition ◽

Sperm Function ◽

Sperm Precedence ◽

Wild Type ◽

Nematode Caenorhabditis Elegans ◽

C Elegans ◽

Normal Sperm ◽

Self Fertilization ◽

Competition Assays

Abstract Hermaphrodite self-fertilization is the primary mode of reproduction in the nematode Caenorhabditis elegans. However, when a hermaphrodite is crossed with a male, nearly all of the oocytes are fertilized by male-derived sperm. This sperm precedence during reproduction is due to the competitive superiority of male-derived sperm and results in a functional suppression of hermaphrodite self-fertility. In this study, mutant males that inseminate fertilization-defective sperm were used to reveal that sperm competition within a hermaphrodite does not require successful fertilization. However, sperm competition does require normal sperm motility. Additionally, sperm competition is not an absolute process because oocytes not fertilized by male-derived sperm can sometimes be fertilized by hermaphrodite-derived sperm. These results indicate that outcrossed progeny result from a wild-type cross because male-derived sperm are competitively superior and hermaphrodite-derived sperm become unavailable to oocytes. The sperm competition assays described in this study will be useful in further classifying the large number of currently identified mutations that alter sperm function and development in C. elegans.

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