scholarly journals Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4317
Author(s):  
Yan-Xi Chen ◽  
Phuong Thu Nguyen Le ◽  
Tsai-Teng Tzeng ◽  
Thu-Ha Tran ◽  
Anh Thuc Nguyen ◽  
...  
Keyword(s):  
Model Systems ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
Cancer Cell Growth ◽  
C Elegans ◽  
Age Related ◽  
Ampk Activity ◽  
Β Amyloid ◽  
Amp Activated Protein Kinase ◽  
U87 Cells

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer’s disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses β-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Sperm Competition in the Absence of Fertilization in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 201-208 ◽  
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.

scholarly journals Genetic, Behavioral and Environmental Determinants of Male Longevity in Caenorhabditis elegans

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1597-1610 ◽  
Author(s):  
David Gems ◽  
Donald L Riddle
Keyword(s):  
Caenorhabditis Elegans ◽  
Life Span ◽  
Wild Type ◽  
Neuronal Function ◽  
Nematode Caenorhabditis Elegans ◽  
Wild Isolate ◽  
Young Males ◽  
C Elegans ◽  
Single Sex ◽  
Solitary Males

Abstract Males of the nematode Caenorhabditis elegans are shorter lived than hermaphrodites when maintained in single-sex groups. We observed that groups of young males form clumps and that solitary males live longer, indicating that male-male interactions reduce life span. By contrast, grouped or isolated hermaphrodites exhibited the same longevity. In one wild isolate of C. elegans, AB2, there was evidence of copulation between males. Nine uncoordinated (unc) mutations were used to block clumping behavior. These mutations had little effect on hermaphrodite life span in most cases, yet many increased male longevity even beyond that of solitary wild-type males. In one case, the neuronal function mutant unc-64(e246), hermaphrodite life span was also increased by up to 60%. The longevity of unc-4(e120), unc-13(e51), and unc-32(e189) males exceeded that of hermaphrodites by 70–120%. This difference appears to reflect a difference in sex-specific life span potential revealed in the absence of male behavior that is detrimental to survival. The greater longevity of males appears not to be affected by daf-2, but is influenced by daf-16. In the absence of male-male interactions, median (but not maximum) male life span was variable. This variability was reduced when dead bacteria were used as food. Maintenance on dead bacteria extended both male and hermaphrodite longevity.

AMP kinase is not required for the GLUT4 response to exercise and denervation in skeletal muscle

2004 ◽  
Vol 287 (4) ◽  
pp. E739-E743 ◽  
Author(s):  
Burton F. Holmes ◽  
David B. Lang ◽  
Morris J. Birnbaum ◽  
James Mu ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Dominant Negative ◽  
Treadmill Running ◽  
Wild Type ◽  
Α Subunit ◽  
Ampk Activity ◽  
Denervated Muscles ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise

An acute bout of exercise increases muscle GLUT4 mRNA in mice, and denervation decreases GLUT4 mRNA. AMP-activated protein kinase (AMPK) activity in skeletal muscle is also increased by exercise, and GLUT4 mRNA is increased in mouse skeletal muscle after treatment with AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside(AICAR). These findings suggest that AMPK activation might be responsible for the increase in GLUT4 mRNA expression in response to exercise. To investigate the role of AMPK in GLUT4 regulation in response to exercise and denervation, transgenic mice with a mutated AMPK α-subunit (dominant negative; AMPK-DN) were studied. GLUT4 did not increase in AMPK-DN mice that were treated with AICAR, demonstrating that muscle AMPK is inactive. Exercise (two 3-h bouts of treadmill running separated by 1 h of rest) increased GLUT4 mRNA in both wild-type and AMPK-DN mice. Likewise, denervation decreased GLUT4 mRNA in both wild-type and AMPK-DN mice. GLUT4 mRNA was also increased by AICAR treatment in both the innervated and denervated muscles. These data demonstrate that AMPK is not required for the response of GLUT4 mRNA to exercise and denervation.

scholarly journals Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 145-154
Author(s):  
I Katsura ◽  
K Kondo ◽  
T Amano ◽  
T Ishihara ◽  
M Kawakami
Keyword(s):  
Caenorhabditis Elegans ◽  
Brood Size ◽  
Normal Growth ◽  
Fluoride Ion ◽  
Wild Type ◽  
Signal Transduction System ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Class 1 ◽  
Resistant Mutants

Abstract We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.

Rubidium chloride increases lifespan through an AMPK/FOXO-dependent pathway in Caenorhabditis elegans

2021 ◽  
Author(s):  
Mengjiao Hao ◽  
Zhikang Zhang ◽  
Yijun Guo ◽  
Huihao Zhou ◽  
Qiong Gu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Aging Effect ◽  
Stress Effect ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Cycle Arrest ◽  
Age Related ◽  
Promising Target ◽  
Amp Activated Protein Kinase

Abstract AMP-activated protein kinase (AMPK) is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. AMPK is currently considered a promising target for preventing age-related diseases. Rubidium is one of the trace elements in human body. As early as the 1970s, RbCl has been was reported to have neuroprotective effects. In this work, we report the anti-aging effect of RbCl in Caenorhabditis elegans. Specifically, we reveal that (1) RbCl does increase the lifespan and enhance stress resistance in C. elegans without disturbing their fecundity. (2) RbCl induces superoxide dismutase (SOD) expression, which is essential for its anti-aging and anti-stress effect. (3) AAK-2 and DAF-16 are essential to the anti-aging efficacy of RbCl, and RbCl can promote DAF-16 translocating into the nucleus, suggesting that RbCl delays aging through regulating AMPK/FOXO pathway. RbCl can be a promising agent against aging related diseases.

scholarly journals ESPO/ BIOLOGICAL SCIENCES SECTION SYMPOSIUM: EMERGING INSIGHTS IN INTERACTIONS AND NETWORKS IN THE BIOLOGY OF AGING DEVELOPING C. ELEGANS TO STUDY AGE-RELATED EXTRACELLULAR VESICLE SIGNALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S424-S424
Author(s):  
Joshua Russell ◽  
Matt Kaeberlein
Keyword(s):  
Biological Sciences ◽  
Mammalian Cell Culture ◽  
Extracellular Vesicle ◽  
Model Systems ◽  
C Elegans ◽  
Physiological Processes ◽  
Age Related ◽  
Powerful Approach ◽  
Invertebrate Model ◽  
Biology Of Aging

Abstract All cells release vesicles into their extracellular environment. These extracellular vesicles (EVs) contain multiple classes of molecules, including nucleic acids, proteins, and lipids. EV-signaling has been shown to be impacted by many age-related physiological processes such as inflammation, mitochondrial stress, and autophagy as well as directly mediate critical functions in cellular senescence and aging. The isolation and analysis of EV cargos from mammalian cell culture and liquid biopsy samples has become a powerful approach for uncovering the messages that are packaged into these organelles. Caenorhabditis elegans is a premier model for dissecting the genetics of aging however, EV analysis has not been tenable in invertebrate model systems due to lack of methods for obtaining sufficient amounts of pure EVs. We developed a method for isolating pure EVs from C. elegans with yields sufficient for mass spectrometry and RNAseq. Here we present the analysis of the genetic and protein cargos of EVs collected from wild type and long-lived mutants collected at different time points across their lifespans. As the first investigation of age-related EV signals in an invertebrate model system we believe these results will provide insights into cell non-autonomous mechanisms of aging.

scholarly journals Electrophysiological Measures of Aging Pharynx Function in C. elegans Reveal Enhanced Organ Functionality in Older, Long-lived Mutants

2017 ◽  
Vol 74 (8) ◽  
pp. 1173-1179 ◽  
Author(s):  
Joshua Coulter Russell ◽  
Nikolay Burnaevskiy ◽  
Bridget Ma ◽  
Miguel Arenas Mailig ◽  
Franklin Faust ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Life Span ◽  
Insulin Signaling ◽  
Model System ◽  
Wild Type ◽  
Organ Function ◽  
C Elegans ◽  
Age Related ◽  
The Relationship

Abstract The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with life span and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and life span, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms (EPG) of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 EPGs from 1,374 individuals. As expected, the long-lived daf-2(e1370) and hsf-1OE(uthIs235) animals maintained pharynx function relatively closer to the youthful state during aging, whereas the hsf-1(sy441) and wild type animals’ pharynx function deviated significantly further from the youthful state at advanced age. Measures of the amount of variation in organ function can act as biomarkers of youthful physiology as well. Intriguingly, the long-lived animals had greater variation in the duration of pharynx contraction at older ages.

scholarly journals Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α1-AMPK−/− mice

2011 ◽  
Vol 301 (2) ◽  
pp. R473-R483 ◽  
Author(s):  
Jake D. Bauwens ◽  
Eric G. Schmuck ◽  
Christopher R. Lindholm ◽  
Rebecca L. Ertel ◽  
Jacob D. Mulligan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Whole Body ◽  
Nonshivering Thermogenesis ◽  
Wild Type ◽  
Brown Adipose ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Established Role

Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might be an effective way of expending excess calories. Because of the established role of AMP-activated protein kinase (AMPK) as a “metabolic master switch” and its extremely high levels of activity in BAT, it was hypothesized that AMPK might play a central role in regulating BAT metabolism. To test this hypothesis, whole body α1-AMPK−/− (knockout) and wild-type mice were studied 1) under control (room temperature) conditions, 2) during chronic cold exposure (14 days at 4°C), and 3) during acute nonshivering thermogenesis (injection of a β3-adrenergic agonist). Under control conditions, loss of α1-AMPK resulted in downregulation of two important prothermogenic genes in BAT, thyrotropin-releasing hormone (−9.2-fold) and ciliary neurotrophic factor (−8.7-fold). Additionally, it caused significant upregulation of α2-AMPK activity in BAT, white adipose tissue, and liver, but not cardiac or skeletal muscle. During acute nonshivering thermogenesis and chronic cold exposure, body temperature was indistinguishable in the α1-AMPK−/− and wild-type mice. Similarly, the degree of cold-induced hyperphagia was identical in the two groups. We conclude that α1-AMPK does not play an obligatory role in these processes and that adaptations to chronic loss of α1-AMPK are able to compensate for its loss via several mechanisms.

scholarly journals Altered expression of an L1-specific, O-linked cuticle surface glycoprotein in mutants of the nematode Caenorhabditis elegans.

1991 ◽  
Vol 115 (5) ◽  
pp. 1237-1247 ◽  
Author(s):  
R M Hemmer ◽  
S G Donkin ◽  
K J Chin ◽  
D G Grenache ◽  
H Bhatt ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Specific Antigen ◽  
Surface Glycoprotein ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
Altered Expression ◽  
C Elegans ◽  
Larval Stages ◽  
Sds Page ◽  
Free Living Nematode

Mouse mAb M38 was used in indirect immunofluorescence experiments to detect a stage-specific antigen on the surface of the first larval stage (L1) of the free-living nematode Caenorhabditis elegans, and to detect alterations in the apparent expression of this antigen in two distinct classes of C. elegans mutants. In previously described srf-2 and srf-3 mutants (Politz S. M., M. T. Philipp, M. Estevez, P.J. O'Brien, and K. J. Chin. 1990. Proc. Natl. Acad. Sci. USA. 87:2901-2905), the antigen is not detected on the surface of any stage. Conversely, in srf-(yj43) and other similar mutants, the antigen is expressed on the surface of the first through the fourth (L4) larval stages. To understand the molecular basis of these alterations, the antigen was characterized in gel immunoblotting experiments. After SDS-PAGE separation and transfer to nitrocellulose, M38 detected a protein antigen in extracts of wild-type L1 populations. The antigen was sensitive to digestion by Pronase and O-glycanase (endo-alpha-N-acetylgalactosaminidase), suggesting that it is an O-linked glycoprotein. This antigen was not detected in corresponding extracts of wild-type L4s or srf-2 or srf-3 L1s, but was detected in extracts of srf-(yj43) L4s. The antigen-defective phenotype of srf-3 was epistatic to the heterochronic mutant phenotype of srf-(yj43) in immunofluorescence tests of the srf-3 srf-(yj43) double mutant, suggesting that srf-(yj43) causes incorrect regulation of a pathway of antigen formation that requires wild-type srf-3 activity.

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