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Elegans aging

Meenakshi Ravichandran, Steffen Priebe, Giovanna Grigolon, Leonid Rozanov, Marco Groth, Beate Laube, Reinhard Guthke, Matthias Platzer, Kim Zarse, Michael Ristow
Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase (GCAT, EC Impairing gcat expression promotes the lifespan of C. elegans by interfering with threonine catabolism to promote methylglyoxal (MGO; CAS 78-98-8) formation in an amine oxidase-dependent manner. MGO is a reactive dicarbonyl inducing diabetic complications in mammals by causing oxidative stress and damaging cellular components, including proteins...
March 3, 2018: Cell Metabolism
Lucie Sauzéat, Anne Laurençon, Vincent Balter
Ageing is accompanied by important chemical deregulations resulting in bodily metal imbalances. The way and extent to which these deregulations are associated with ageing processes are however poorly understood and their use as potential biomarkers of ageing has not been investigated. In this study, we report whole-body elementary concentrations and copper and zinc isotopic compositions of Caenorhabditis elegans in ageing wild type (i.e. 'normal'-lived) and mutant (i.e. short and long-lived) strains. We show that the strains are characterized by different levels of mutation-related variations such as in phosphorus and magnesium as well as in zinc isotopic composition...
March 14, 2018: Metallomics: Integrated Biometal Science
Debarati Chattopadhyay, Kavitha Thirumurugan
Past investigations have shown that various plant extracts are capable of promoting longevity in lower model organisms like Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Bombyx mori etc. Longevity studies on such organisms provide a foundation to explore anti-aging efficacies of such plant extracts in higher organisms. Plant extracts of acai palm, apple, asparagus, blueberry, cinnamon, cocoa, Damnacanthus, maize, mistletoe, peach, pomegranate, Rhodiola, rose, Sasa, turmeric, and Withania have extended lifespan in lower model organisms via diverse mechanisms like insulin like growth factor (IGF) signaling pathway, and antioxidant defense mechanisms...
March 8, 2018: Mechanisms of Ageing and Development
Lin Zhou, Lu Wang, Shuju Bai, Shu Xing, Wannan Li, Junfeng Ma, Xueqi Fu
Low molecular weight protein tyrosine phosphatase (LMW-PTP) is highly conserved across almost all living organisms and is involved in the modulation of a number of cellular proteins related to important signaling pathways. In this study, we isolated lmwptp (Y94H6A.7) of Caenorhabditis elegans, the homolog of human ACP1, and set up an effective feeding-based RNA interference (RNAi) knockdown against this gene. We found that knockdown of lmwptp decreased damage associated with heat shock, oxidative stress and UV irradiation in wild-type worms, however, its deficiency didn't further reduce the stress resistance of hsf-1 or daf-16 mutants and didn't further increase the stress sensitivity associated with age-1, akt-1 or akt-2 mutants, but it enhanced the stress resistance of daf-2 mutants...
March 7, 2018: International Journal of Biological Macromolecules
Yujuan Li, Shuwen Guan, Cong Liu, Xinhua Chen, Yuemei Zhu, Yutong Xie, Jianbin Wang, Xue Ji, Liqin Li, Zhuohan Li, Yue Zhang, Xiangzhi Zeng, Mingquan Li
This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on Aβ1-42 transgenic CL4176 Caenorhabditis elegans, as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100 mg/L > 500 mg/L > 200 mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100 mg/L could delay the paralysis rate of C...
March 7, 2018: International Journal of Biological Macromolecules
Aristeidis P Sfakianos, Laura E Mellor, Yoke Fei Pang, Paraskevi Kritsiligkou, Hope Needs, Hussein Abou-Hamdan, Laurent Désaubry, Gino B Poulin, Mark P Ashe, Alan J Whitmarsh
Stress granules are cytoplasmic mRNA-protein complexes that form upon the inhibition of translation initiation and promote cell survival in response to environmental insults. However, they are often associated with pathologies, including neurodegeneration and cancer, and changes in their dynamics are implicated in ageing. Here we show that the mTOR effector kinases S6 kinase 1 (S6K1) and S6 kinase 2 (S6K2) localise to stress granules in human cells and are required for their assembly and maintenance after mild oxidative stress...
March 9, 2018: Cell Death and Differentiation
Ata Ghavidel, Kunal Baxi, Martin Prusinkiewicz, Cynthia Swan, Zach R Belak, Christopher H Eskiw, Carlos E Carvalho, Troy A Harkness
The yeast, Saccharomyces cerevisiae , like other higher eukaryotes, undergo a finite number of cell divisions before exiting the cell cycle due to the effects of aging. Here, we show that yeast aging begins with the nuclear exclusion of Hcm1 in young cells, resulting in loss of acidic vacuoles. Autophagy is required for healthy aging in yeast, with proteins targeted for turnover by autophagy directed to the vacuole. Consistent with this, vacuolar acidity is necessary for vacuolar function and yeast longevity...
March 8, 2018: G3: Genes—Genomes—Genetics
Yujie Li, Sandra Finkbeiner, Athina Ganner, Julia Gerber, Marinella Klein, Manuel Grafe, Jakob Kandzia, Antje Thien, Kathrin Thedieck, Gerhard Breves, Thomas Jank, Ralf Baumeister, Gerd Walz, Elke Neumann-Haefelin
The mechanistic target of rapamycin (mTOR) kinase is central to metabolism and growth, and has a conserved role in aging. mTOR functions in two complexes, mTORC1 and mTORC2. In diverse eukaryotes, inhibition of mTORC1 signaling increases lifespan. mTORC1 transduces anabolic signals to stimulate protein synthesis and inhibits autophagy. In this study, we demonstrate that CGEF-1, the C. elegans homolog of the human guanine nucleotide exchange factor Dbl, is a novel binding partner of RHEB-1 and activator of mTORC1 signaling in C...
February 9, 2018: Oncotarget
Liangping Su, Hongyuan Li, Cheng Huang, Tingting Zhao, Yongjun Zhang, Xueqing Ba, Zhongwei Li, Yu Zhang, Baiqu Huang, Jun Lu, Yanmei Zhao, Xiaoxue Li
Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway...
March 6, 2018: Cell Reports
Yonghak Seo, Samuel Kingsley, Griffin Walker, Michelle A Mondoux, Heidi A Tissenbaum
As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans , excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexey Moskalev, Mikhail Shaposhnikov, Nadezhda Zemskaya, Alexey Belyi, Eugenia Dobrovolskaya, Anna Patova, Zulfiya Guvatova, Elena Lukyanova, Anastasiya Snezhkina, Anna Kudryavtseva
BACKGROUND: We have previously showed that the carotenoid fucoxanthin can increase the lifespan in Drosophila melanogaster and Caenorhabditis elegans. However, the molecular mechanisms of the geroprotective effect of fucoxanthin have not been studied so far. RESULTS: Here, we studied the effects of fucoxanthin on the Drosophila aging process at the molecular and the whole organism levels. At the organismal level, fucoxanthin increased the median lifespan and had a positive effect on fecundity, fertility, intestinal barrier function, and nighttime sleep...
February 9, 2018: BMC Genomics
Herbenya Peixoto, Mariana Roxo, Hector Koolen, Felipe da Silva, Emerson Silva, Markus Santhosh Braun, Xiaojuan Wang, Michael Wink
The tree popularly known in Brazil as mulateiro or pau-mulato ( Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bernadette Hotzi, Mónika Kosztelnik, Balázs Hargitai, Krisztina Takács-Vellai, János Barna, Kincső Bördén, András Málnási-Csizmadia, Mónika Lippai, Csaba Ortutay, Caroline Bacquet, Angela Pasparaki, Tamás Arányi, Nektarios Tavernarakis, Tibor Vellai
A fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3-7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites-which are essentially females capable of sperm production-over males is established by TRA-1, the terminal effector of the sex-determination pathway...
March 1, 2018: Aging Cell
Bi Zhang, Jianke Gong, Wenyuan Zhang, Rui Xiao, Jianfeng Liu, X Z Shawn Xu
Tissue-tissue communications are integral to organismal aging, orchestrating a body-wide aging process. The brain plays a key role in this process by detecting and processing signals from the environment and then communicating them to distal tissues such as the gut to regulate longevity. How this is achieved, however, is poorly understood. Here, using Caenorhabditis elegans as a model, we identified two distinct neuroendocrine signaling circuits by which the worm nervous system senses cool and warm environmental temperatures through cool- and warm-sensitive neurons and then signals the gut to extend and shorten life span, respectively...
February 1, 2018: Genes & Development
Federico Pietrocola, Francesca Castoldi, Maria Markaki, Sylvie Lachkar, Guo Chen, David P Enot, Sylvere Durand, Noelie Bossut, Mingming Tong, Shoaib A Malik, Friedemann Loos, Nicolas Dupont, Guillermo Mariño, Nejma Abdelkader, Frank Madeo, Maria Chiara Maiuri, Romano Kroemer, Patrice Codogno, Junichi Sadoshima, Nektarios Tavernarakis, Guido Kroemer
The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300...
February 27, 2018: Cell Reports
Stijn Mouton, Magda Grudniewska, Lisa Glazenburg, Victor Guryev, Eugene Berezikov
Animals show a large variability of lifespan, ranging from short-lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation-by-regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free-living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed...
February 28, 2018: Aging Cell
Jason F Cooper, Jeremy M Van Raamsdonk
Parkinson's disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens for disease modifiers...
2018: Journal of Parkinson's Disease
Nicole M Templeman, Shijing Luo, Rachel Kaletsky, Cheng Shi, Jasmine Ashraf, William Keyes, Coleen T Murphy
A decline in female reproduction is one of the earliest hallmarks of aging in many animals, including invertebrates and mammals [1-4]. The insulin/insulin-like growth factor-1 signaling (IIS) pathway has a conserved role in regulating longevity [5] and also controls reproductive aging [2, 6]. Although IIS transcriptional targets that regulate somatic aging have been characterized [7, 8], it was not known whether the same mechanisms influence reproductive aging. We previously showed that Caenorhabditis elegans daf-2 IIS receptor mutants extend reproductive span by maintaining oocyte quality with age [6], but IIS targets in oocytes had not been identified...
February 22, 2018: Current Biology: CB
Jie-Bin Zhou, Ying-Lin Zheng, Yi-Xuan Zeng, Jia-Wei Wang, Zhong Pei, Ji-Yan Pang
Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms...
February 10, 2018: European Journal of Medicinal Chemistry
Dhaval Patel, Chuan Xu, Sureshbabu Nagarajan, Zhengchang Liu, Wayne O Hemphill, Runhua Shi, Vladimir N Uversky, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We probed the role of alpha-synuclein (α-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound multicopper ferroxidase, whose ferroxidase domain is orthologous to human ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then channel through the Ftr1 permease into the cell. When the concentration of external iron is low (< 1 µM), Fet3/Ftr1 is maintained on the plasma membrane by retrograde endocytic-recycling; whereas, when the concentration of external iron is high (> 10 µM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for degradation...
February 14, 2018: Human Molecular Genetics
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