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  1. Article ; Online: Neuronal waste management: new roles for autophagy genes in the extrusion of protein aggregates and in longevity.

    Sun, Ling-Hsuan / Lange, Caitlin M / Hansen, Malene / Kumsta, Caroline

    Autophagy

    2024  , Page(s) 1–3

    Abstract: A decline in macroautophagic/autophagic activity with age contributes to the accumulation of damaged molecules and is associated with the impairment of neuronal functions and the onset of age-related diseases, particularly neurodegenerative disorders. To ...

    Abstract A decline in macroautophagic/autophagic activity with age contributes to the accumulation of damaged molecules and is associated with the impairment of neuronal functions and the onset of age-related diseases, particularly neurodegenerative disorders. To learn about the neuronal-specific roles of autophagy genes in aging, we specifically inhibited autophagy genes pan-neuronally in
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2024.2322420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Getting under the skin: Cuticle damage elicits systemic autophagy response in

    Kumsta, Caroline / Hansen, Malene

    The Journal of cell biology

    2019  Volume 218, Issue 12, Page(s) 3885–3887

    Abstract: In this issue, Zhang et al. (2019. ...

    Abstract In this issue, Zhang et al. (2019.
    MeSH term(s) Animals ; Autophagy ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins ; Transforming Growth Factor beta
    Chemical Substances Caenorhabditis elegans Proteins ; DAF-7 protein, C elegans ; Transforming Growth Factor beta
    Language English
    Publishing date 2019-11-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.201911020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Assessing Tissue-Specific Autophagy Flux in Adult Caenorhabditis elegans.

    Chang, Jessica T / Hansen, Malene / Kumsta, Caroline

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2144, Page(s) 187–200

    Abstract: The cellular recycling process of autophagy is essential for survival, development, and homeostasis. Autophagy also plays an important role in aging and has been linked to longevity in many species, including the nematode C. elegans. Study of the ... ...

    Abstract The cellular recycling process of autophagy is essential for survival, development, and homeostasis. Autophagy also plays an important role in aging and has been linked to longevity in many species, including the nematode C. elegans. Study of the physiological roles of autophagy during C. elegans aging requires methods for the spatiotemporal analysis of autophagy. Here we describe a method for assessing autophagic flux in multiple tissues of C. elegans by quantifying the pool of autophagic vesicles using fluorescently labelled Atg8/LGG-1 reporters upon autophagy inhibition using bafilomycin A
    MeSH term(s) Aging/genetics ; Animals ; Autophagy/genetics ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans Proteins/genetics ; Longevity/genetics ; Microtubule-Associated Proteins/genetics ; Molecular Biology/methods
    Chemical Substances Caenorhabditis elegans Proteins ; Microtubule-Associated Proteins
    Language English
    Publishing date 2020-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0592-9_17
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction to: Assessing Tissue-Specific Autophagy Flux in Adult Caenorhabditis elegans.

    Chang, Jessica T / Hansen, Malene / Kumsta, Caroline

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2144, Page(s) C1

    Abstract: Correction to: Chapter 17 in: Sean P. Curran (ed.), Aging: Methods and Protocols, Methods in Molecular Biology, vol. 2144. ...

    Abstract Correction to: Chapter 17 in: Sean P. Curran (ed.), Aging: Methods and Protocols, Methods in Molecular Biology, vol. 2144.
    Language English
    Publishing date 2020-08-04
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0592-9_24
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  5. Article ; Online: Hormetic heat shock and HSF-1 overexpression improve C. elegans survival and proteostasis by inducing autophagy.

    Kumsta, Caroline / Hansen, Malene

    Autophagy

    2017  Volume 13, Issue 6, Page(s) 1076–1077

    Abstract: The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and ... ...

    Abstract The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and physiologically beneficial ("hormetic") heat shock as well as overexpression of the heat-shock responsive transcription factor HSF-1 systemically increases autophagy in C. elegans. Accordingly, we found HSF-1- and heat stress-inducible autophagy to be required for C. elegans thermoresistance and longevity. Moreover, a hormetic heat shock or HSF-1 overexpression alleviated PolyQ protein aggregation in an autophagy-dependent manner. Collectively, we demonstrate a critical role for autophagy in C. elegans stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1 regulated functions in the heat-shock response, proteostasis, and aging.
    Language English
    Publishing date 2017-06-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2017.1299313
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  6. Article ; Online: Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons.

    Yang, Yongzhi / Arnold, Meghan Lee / Lange, Caitlin M / Sun, Ling-Hsuan / Broussalian, Michael / Doroodian, Saam / Ebata, Hiroshi / Choy, Elizabeth H / Poon, Karie / Moreno, Tatiana M / Singh, Anupama / Driscoll, Monica / Kumsta, Caroline / Hansen, Malene

    Nature aging

    2024  Volume 4, Issue 2, Page(s) 198–212

    Abstract: While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, ... ...

    Abstract While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Longevity/genetics ; Neurons/metabolism ; Autophagy/genetics ; Mammals/metabolism
    Chemical Substances Caenorhabditis elegans Proteins
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ISSN 2662-8465
    ISSN (online) 2662-8465
    DOI 10.1038/s43587-023-00548-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The selective autophagy receptor SQSTM1/p62 improves lifespan and proteostasis in an evolutionarily conserved manner.

    Aparicio, Ricardo / Hansen, Malene / Walker, David W / Kumsta, Caroline

    Autophagy

    2020  Volume 16, Issue 4, Page(s) 772–774

    Abstract: The degradation of specific cargos such as ubiquitinated protein aggregates and dysfunctional mitochondria via macroautophagy/autophagy is facilitated by SQSTM1/p62, the first described selective autophagy receptor in metazoans. While the general process ...

    Abstract The degradation of specific cargos such as ubiquitinated protein aggregates and dysfunctional mitochondria via macroautophagy/autophagy is facilitated by SQSTM1/p62, the first described selective autophagy receptor in metazoans. While the general process of autophagy plays crucial roles during aging, it remains unclear whether and how selective autophagy mediates effects on longevity and health. Two recent studies in the nematode
    MeSH term(s) Animals ; Autophagy/physiology ; Caenorhabditis elegans/metabolism ; Drosophila melanogaster/metabolism ; Humans ; Longevity/physiology ; Mitochondria/metabolism ; Proteostasis/physiology ; Sequestosome-1 Protein/metabolism
    Chemical Substances SQSTM1 protein, human ; Sequestosome-1 Protein
    Language English
    Publishing date 2020-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2020.1725404
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  8. Article: Cellular effects of oxidative stress on C. elegans

    Kumsta, Caroline

    Futura

    2010  Volume 25, Issue 3, Page(s) 243

    Language German ; English
    Document type Article
    ZDB-ID 382906-6
    ISSN 0179-6372
    Database Current Contents Medicine

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    Zs.B 2980: Show issues Location:
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  9. Article ; Online: C. elegans rrf-1 mutations maintain RNAi efficiency in the soma in addition to the germline.

    Kumsta, Caroline / Hansen, Malene

    PloS one

    2012  Volume 7, Issue 5, Page(s) e35428

    Abstract: Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in ... ...

    Abstract Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in distinct tissues. In this study we characterized C. elegans rrf-1 mutants to determine their ability to process RNAi in various tissues. These mutants have been widely used in RNAi studies to assess the function of genes specifically in the C. elegans germline. Upon closer analysis, we found that two rrf-1 mutants carrying different loss-of-function alleles were capable of processing RNAi targeting several somatically expressed genes. Specifically, we observed that the intestine was able to process RNAi triggers efficiently, whereas cells in the hypodermis showed partial susceptibility to RNAi in rrf-1 mutants. Other somatic tissues in rrf-1 mutants, such as the muscles and the somatic gonad, appeared resistant to RNAi. In addition to these observations, we found that the rrf-1(pk1417) mutation induced the expression of several transgenic arrays, including the FOXO transcription factor DAF-16. Unexpectedly, rrf-1(pk1417) mutants showed increased endogenous expression of the DAF-16 target gene sod-3; however, the lifespan and thermo-tolerance of rrf-1(pk1417) mutants were similar to those of wild-type animals. In sum, these data show that rrf-1 mutants display several phenotypes not previously appreciated, including broader tissue-specific RNAi-processing capabilities, and our results underscore the need for careful characterization of tissue-specific RNAi tools.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Female ; Forkhead Transcription Factors ; Gene Expression Regulation/genetics ; Genes, Reporter/genetics ; Intestinal Mucosa/metabolism ; Male ; Mutation ; Organ Specificity ; Ovum/growth & development ; Ovum/metabolism ; RNA Interference ; RNA-Dependent RNA Polymerase/genetics ; RNA-Dependent RNA Polymerase/metabolism ; Spermatozoa/growth & development ; Spermatozoa/metabolism ; Subcutaneous Tissue/metabolism ; Superoxide Dismutase/deficiency ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Transcription Factors/deficiency ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; Forkhead Transcription Factors ; Transcription Factors ; daf-16 protein, C elegans ; Sod-3 protein, C elegans (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; RRF-1 protein, C elegans (EC 2.7.7.48)
    Language English
    Publishing date 2012-05-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0035428
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans.

    Kumsta, Caroline / Chang, Jessica T / Schmalz, Jessica / Hansen, Malene

    Nature communications

    2017  Volume 8, Page(s) 14337

    Abstract: Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as ... ...

    Abstract Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as hormesis. Although the universally conserved heat-shock response regulated by transcription factor HSF-1 has been implicated as an effector mechanism, the role and possible interplay with other cellular processes, such as autophagy, remains poorly understood. Here we show that autophagy is induced in multiple tissues of Caenorhabditis elegans following hormetic heat stress or HSF-1 overexpression. Autophagy-related genes are required for the thermoresistance and longevity of animals exposed to hormetic heat shock or HSF-1 overexpression. Hormetic heat shock also reduces the progressive accumulation of PolyQ aggregates in an autophagy-dependent manner. These findings demonstrate that autophagy contributes to stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1-regulated functions in the heat-shock response, proteostasis and ageing.
    MeSH term(s) Animals ; Autophagy ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Gene Expression Regulation ; Green Fluorescent Proteins/metabolism ; Heat-Shock Response ; Hormesis ; Peptides/metabolism ; Protein Aggregates ; Proteostasis ; Survival Analysis ; Transcription Factors/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; Peptides ; Protein Aggregates ; Transcription Factors ; heat shock factor-1, C elegans ; Green Fluorescent Proteins (147336-22-9) ; polyglutamine (26700-71-0)
    Language English
    Publishing date 2017-02-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms14337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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