scholarly journals Odor Sensitivity as a Biomarker of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 121-122
Author(s):  
Marjana Sarker ◽  
Scott Leiser
Keyword(s):  
Olfactory System ◽  
Healthy Adult ◽  
Model Organism ◽  
Olfactory Neurons ◽  
Adult Lifespan ◽  
C Elegans ◽  
Short Lifespan ◽  
Age Related ◽  
Odor Sensitivity ◽  
Biomarker Of Aging

Abstract Recent studies support the deterioration of the sense of smell as an important biomarker for cognitive impairment diseases, including Alzheimer’s disease. The model organism C. elegans has a well-studied olfactory system, which provides an ideal platform to measure loss of smell with aging. The goal of our project is to use the short lifespan and olfactory changes observed in nematodes to identify mechanisms to slow aging and treat age-related diseases. Our approach is to utilize worms at various times of their healthy adult lifespan and to test for their sensitivity to known attractants such as benzaldehyde. These odorants are largely detected by the main AWC olfactory neurons. It is well documented that the responsiveness of AWC decreases with age. Our paradigm is to briefly fast worms to increase motivation before testing their ability to discriminate odors. Our results show that younger worms actively move toward the attractant and show preference for specific attractants. However, older worms frequently do not respond to attractive odors and remain near the point of origin, regardless of motility. These results indicate a decreased odor response with age. Our current work focuses on identifying genes and compounds that positively affect this odor response in older animals. The resulting data can then be tested for their efficacy to improve other aspects of healthspan and potentially longevity.

scholarly journals LONGEVITY OVER THE COUNTER: INVESTIGATING THE EFFECTS OF COMMON DIETARY SUPPLEMENTS ON AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S102-S103
Author(s):  
Ben Blue ◽  
Elena Vayndorf ◽  
Matt Kaeberlein
Keyword(s):  
Body Wall ◽  
Video Recording ◽  
The Body ◽  
Limiting Factor ◽  
Time Of Death ◽  
Image Capture ◽  
Over The Counter ◽  
C Elegans ◽  
Short Lifespan ◽  
Age Related

Abstract C. elegans has been a workhorse within the field of aging biology for several decades due to its short lifespan, easy culturing, and robust genetic tools. However, the limiting factor in using C. elegans has been that throughput was constrained by the time and effort needed to manually check the worms for signs of life during longitudinal studies. By using the WormBot, a robotic image capture platform, we are able to successfully screen a wide array of compounds for their effects upon C. elegans lifespan. A single WormBot can monitor 144 individual experiments simultaneously and allows for accurate time of death calls. Here we present data generated with the WormBot that includes a screen of compounds from a wide array of natural and synthetic products that are often available as over-the-counter supplements. In order to better examine the effects of these widely-used compounds upon the aging process and an age-associated disease we examined longevity in a wildtype strain of C. elegans as well as an engineered strain that expresses human Aβ protein in the body wall muscle. The age-related pathogenesis of the Aβ-expressing strain is a progressive paralysis that can be halted with treatment of known effectors of Alzheimer’s disease. As such, we screened our battery of compounds with this strain to determine which compounds have a significant affect on delaying Aβ-associated paralysis. Lastly, using the WormBot’s ability to capture video recording, we examine how each compound affects mobility as animals age.

scholarly journals C. elegans Models to Study the Propagation of Prions and Prion-Like Proteins

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1188 ◽  
Author(s):  
Carl Alexander Sandhof ◽  
Simon Oliver Hoppe ◽  
Jessica Tittelmeier ◽  
Carmen Nussbaum-Krammer
Keyword(s):  
Neurodegenerative Diseases ◽  
Model Organism ◽  
Model Systems ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
Population Demographics ◽  
C Elegans ◽  
Age Related ◽  
Bona Fide ◽  
High Degree

A hallmark common to many age-related neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), is that patients develop proteinaceous deposits in their central nervous system (CNS). The progressive spreading of these inclusions from initially affected sites to interconnected brain areas is reminiscent of the behavior of bona fide prions in transmissible spongiform encephalopathies (TSEs), hence the term prion-like proteins has been coined. Despite intensive research, the exact mechanisms that facilitate the spreading of protein aggregation between cells, and the associated loss of neurons, remain poorly understood. As population demographics in many countries continue to shift to higher life expectancy, the incidence of neurodegenerative diseases is also rising. This represents a major challenge for healthcare systems and patients’ families, since patients require extensive support over several years and there is still no therapy to cure or stop these diseases. The model organism Caenorhabditis elegans offers unique opportunities to accelerate research and drug development due to its genetic amenability, its transparency, and the high degree of conservation of molecular pathways. Here, we will review how recent studies that utilize this soil dwelling nematode have proceeded to investigate the propagation and intercellular transmission of prions and prion-like proteins and discuss their relevance by comparing their findings to observations in other model systems and patients.

scholarly journals The Detection of Early Epigenetic Inheritance of Mitochondrial Stress in C. Elegans with a Microfluidic Phenotyping Platform

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
H. B. Atakan ◽  
K. S. Hof ◽  
M. Cornaglia ◽  
J. Auwerx ◽  
M. A. M. Gijs
Keyword(s):  
Dna Sequence ◽  
Drug Exposure ◽  
Model Organism ◽  
Epigenetic Inheritance ◽  
Short Term ◽  
Mitochondrial Stress ◽  
New Device ◽  
C Elegans ◽  
Short Lifespan ◽  
Depth Analysis

AbstractFluctuations and deterioration in environmental conditions potentially have a phenotypic impact that extends over generations. Transgenerational epigenetics is the defined term for such intergenerational transient inheritance without an alteration in the DNA sequence. The model organism Caenorhabditis elegans is exceptionally valuable to address transgenerational epigenetics due to its short lifespan, well-mapped genome and hermaphrodite behavior. While the majority of the transgenerational epigenetics on the nematodes focuses on generations-wide heritage, short-term and in-depth analysis of this phenomenon in a well-controlled manner has been lacking. Here, we present a novel microfluidic platform to observe mother-to-progeny heritable transmission in C. elegans at high imaging resolution, under significant automation, and enabling parallelized studies. After approximately 24 hours of culture of L4 larvae under various concentrations and application periods of doxycycline, we investigated if mitochondrial stress was transferred from the mother nematodes to the early progenies. Automated and custom phenotyping algorithms revealed that a minimum doxycycline concentration of 30 µg/mL and a drug exposure time of 15 hours applied to the mothers could induce mitochondrial stress in first embryo progenies indeed, while this inheritance was not clearly observed later in L1 progenies. We believe that our new device could find further usage in transgenerational epigenetic studies modeled on C. elegans.

scholarly journals High-Content C. elegans Screen Identifies Natural Compounds Impacting Mitochondria-Lipid Homeostasis and Promoting Healthspan

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 100
Author(s):  
Silvia Maglioni ◽  
Nayna Arsalan ◽  
Anna Hamacher ◽  
Shiwa Afshar ◽  
Alfonso Schiavi ◽  
...  
Keyword(s):  
Stress Response ◽  
Lipid Content ◽  
Model Organism ◽  
Natural Compounds ◽  
Extrinsic Factors ◽  
Mitochondrial Stress ◽  
C Elegans ◽  
Stress Response Genes ◽  
Age Related ◽  
Kahalalide F

The aging process is concurrently shaped by genetic and extrinsic factors. In this work, we screened a small library of natural compounds, many of marine origin, to identify novel possible anti-aging interventions in Caenorhabditis elegans, a powerful model organism for aging studies. To this aim, we exploited a high-content microscopy platform to search for interventions able to induce phenotypes associated with mild mitochondrial stress, which is known to promote animal’s health- and lifespan. Worms were initially exposed to three different concentrations of the drugs in liquid culture, in search of those affecting animal size and expression of mitochondrial stress response genes. This was followed by a validation step with nine compounds on solid media to refine compounds concentration, which led to the identification of four compounds (namely isobavachalcone, manzamine A, kahalalide F and lutein) consistently affecting development, fertility, size and lipid content of the nematodes. Treatment of Drosophila cells with the four hits confirmed their effects on mitochondria activity and lipid content. Out of these four, two were specifically chosen for analysis of age-related parameters, kahalalide F and lutein, which conferred increased resistance to heat and oxidative stress and extended animals’ healthspan. We also found that, out of different mitochondrial stress response genes, only the C. elegans ortholog of the synaptic regulatory proteins neuroligins, nlg-1, was consistently induced by the two compounds and mediated lutein healthspan effects.

Anti-aging and Anti-aggregation Properties of Polyphenolic Compounds in C. elegans

2018 ◽  
Vol 24 (19) ◽  
pp. 2107-2120 ◽  
Author(s):  
Nikoletta Papaevgeniou ◽  
Niki Chondrogianni
Keyword(s):  
Oxidative Stress ◽  
Model Organism ◽  
Protective Role ◽  
Polyphenolic Compounds ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Beneficial Effects ◽  
Age Related ◽  
Anti Oxidant ◽  
Main Model

Polyphenols constitute a group of compounds that have been highly investigated for their beneficial effects against various pathologic and non-pathologic conditions and diseases. Among their multi-faceted properties, their anti-oxidant potential nominates them as ideal protective candidates for conditions characterized by elevated levels of oxidative stress, including aging and age-related diseases. The nematode Caenorhabditis elegans is a multicellular model organism that is highly exploited in studies related to aging and age-associated pathologies. In this review, we will summarize studies where polyphenolic compounds have been tested for their anti-aging potential and their protective role against the progression of age-related diseases using C. elegans as their main model.

scholarly journals Glucose availability impacts proteotoxic stress in Caenorhabditis elegans

2019 ◽  
Author(s):  
Landon Gatrell ◽  
Whitney Wilkins ◽  
Priya Rana ◽  
Mindy Farris
Keyword(s):  
Caenorhabditis Elegans ◽  
Huntington Disease ◽  
Model Organism ◽  
Product Formation ◽  
Cag Repeat ◽  
Strongly Correlated ◽  
Energy Deficiency ◽  
C Elegans ◽  
Age Related ◽  
Future Work

AbstractAlterations in protein folding may lead to aggregation of misfolded proteins, which is strongly correlated with neurotoxicity and cell death. Protein aggregation has been shown as a normal consequence of aging, but it is largely associated with age-related disease, particularly neurodegenerative diseases like Huntington disease (HD). Huntington disease is caused by a CAG repeat expansion in the huntingtin gene and serves as a useful model for neurodegeneration due to its strictly genetic origin. Research in the model organism Caenorhabditis elegans suggests that glucose protects against cell stress, including proteotoxicity related to aggregation, despite the well-known, lifespan-shortening effects of glucose. We hypothesized that glucose could be beneficial by alleviating energy deficiency, a well-characterized phenomenon in HD, or by upregulating stress resistance pathways. We used C. elegans expressing polyglutamine repeats to quantify lifespan, motility, reproduction, learning, and activity of succinate dehydrogenase (SDH), with and without glucose, to identify the role of glucose in proteotoxicity and neuroprotection. Our data show HD worms on glucose plates exhibited shorter lifespans, no change in motility, learning, or SDH product formation, but had altered reproductive phenotypes similar to dietary restriction. Additionally, worms expressing toxic polyglutamine repeats were unable to learn association of food with a neutral odorant. We also observed tissue-specific differences; polyglutamine appeared to be slightly more toxic to muscle cells than neurons. Rather than increasing energy production, glucose appeared to decrease mitochondrial metabolism, as SDH formation decreases with added glucose. Future work investigating glucose-mediated neuroprotection should focus on connecting metabolism, sirtuin activation, and DAF-16 activation.

scholarly journals Forward genetic screen forCaenorhabditis elegansmutants with a shortened locomotor healthspan

2018 ◽  
Author(s):  
Kazuto Kawamura ◽  
Ichiro N. Maruyama
Keyword(s):  
Progressive Decline ◽  
Forward Genetic Screen ◽  
C Elegans ◽  
Short Lifespan ◽  
Elongator Complex ◽  
Age Related ◽  
Mutant Strains ◽  
Complex Protein ◽  
Locomotor Impairment ◽  
Locomotor Deficits

AbstractTwo people with the same lifespan do not necessarily have the same healthspan. One person may retain locomotor and cognitive functions until the end of life, while another person may lose them during adulthood. Unbiased searches for genes that are required to maintain locomotor capacities during adulthood may uncover key regulators of locomotor healthspan. Here, we take advantage of the relatively short lifespan of the nematodeCaenorhabditis elegansand develop a novel screening procedure to collect mutants with locomotor deficits that become apparent in adulthood. After ethyl methanesulfonate mutagenesis, we isolated fiveC. elegansmutant strains that progressively lose adult locomotor activity. In one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2)causes a progressive decline in locomotor function. Mutants and mutations identified in the present screen may provide insights into mechanisms of age-related locomotor impairment and the maintenance of locomotor healthspan.

scholarly journals Pollutants corrupt resilience pathways of aging in the nematode C. elegans

2021 ◽  
Author(s):  
Andrea Scharf ◽  
Annette Limke ◽  
Karl-Heinz Guehrs ◽  
Anna von Mikecz
Keyword(s):  
Healthy Aging ◽  
Inorganic Mercury ◽  
Model Organism ◽  
Population Level ◽  
Premature Aging ◽  
Aging Research ◽  
Positive Interventions ◽  
C Elegans ◽  
Age Related ◽  
Genetic Interventions

AbstractDelaying aging while prolonging health and lifespan is a major goal in aging research. While many resources have been allocated to find positive interventions with promising results, negative interventions such as pollution and their accelerating effect on age-related degeneration and disease have been mostly neglected. Here, we used the short-lived model organism C. elegans to analyze whether two candidate pollutants interfere with positive interventions by corrupting general aging pathways. We took advantage of the immense data sets describing the age-related remodeling of the proteome including increased protein insolubilities to complement our analysis. We show that the emergent pollutant silica nanoparticles (NP) and the classic xenobiotic inorganic mercury reduce lifespan and cause a premature protein aggregation phenotype. Silica NPs rescaled the longevity effect of genetic interventions targeting the IGF-1/insulin-like signaling pathway. Comparative mass spectrometry revealed that increased insolubility of proteins with important functions in proteostasis is a shared phenotype of intrinsic- and pollution-induced aging supporting the hypothesis that proteostasis is a central resilience pathway controlling lifespan and aging. The presented data demonstrate that pollutants corrupt intrinsic aging pathways, which results in premature aging phenotypes. Reducing pollution is therefore an important step to increase healthy aging and prolong life expectancies on a population level in humans and animals.

scholarly journals Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Elite Possik ◽  
Clémence Schmitt ◽  
Anfal Al-Mass ◽  
Ying Bai ◽  
Laurence Côté ◽  
...  
Keyword(s):  
Calorie Restriction ◽  
Mammalian Cells ◽  
Healthy Aging ◽  
Model Organism ◽  
Metabolic Stress ◽  
Clinical Importance ◽  
C Elegans ◽  
Beneficial Effects ◽  
Age Related

AbstractMetabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.

scholarly journals Germline Stem and Progenitor Cell Aging in C. elegans

2021 ◽  
Vol 9 ◽  
Author(s):  
Theadora Tolkin ◽  
E. Jane Albert Hubbard
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Progenitor Cell ◽  
Model Organism ◽  
Cell Aging ◽  
Germline Stem Cells ◽  
C Elegans ◽  
Age Related ◽  
Stem And Progenitor Cells ◽  
Molecular Aspects

Like many animals and humans, reproduction in the nematode C. elegans declines with age. This decline is the cumulative result of age-related changes in several steps of germline function, many of which are highly accessible for experimental investigation in this short-lived model organism. Here we review recent work showing that a very early and major contributing step to reproductive decline is the depletion of the germline stem and progenitor cell pool. Since many cellular and molecular aspects of stem cell biology and aging are conserved across animals, understanding mechanisms of age-related decline of germline stem and progenitor cells in C. elegans has broad implications for aging stem cells, germline stem cells, and reproductive aging.

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