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Article ; Online: Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity.

Wu, Ziyun / Isik, Meltem / Moroz, Natalie / Steinbaugh, Michael J / Zhang, Peng / Blackwell, T Keith

2021 Volume 33, Issue 10, Page(s) 2090

Language	English
Publishing date	2021-10-03
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2021.08.016
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Article ; Online: An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement.

Castillo-Quan, Jorge Iván / Steinbaugh, Michael J / Fernández-Cárdenas, Laura Paulette / Pohl, Nancy K / Wu, Ziyun / Zhu, Feimei / Moroz, Natalie / Teixeira, Veronica / Bland, Monet S / Lehrbach, Nicolas J / Moronetti, Lorenza / Teufl, Magdalena / Blackwell, T Keith

Science advances

2023 Volume 9, Issue 1, Page(s) eadc8917

Abstract: Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty acid (FA), promotes health and longevity. Here, we show that OA ... ...

Abstract	Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty acid (FA), promotes health and longevity. Here, we show that OA benefits
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adc8917
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Article ; Online: S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects.

Ogawa, Takafumi / Masumura, Koji / Kohara, Yuki / Kanai, Muneyoshi / Soga, Tomoyoshi / Ohya, Yoshikazu / Blackwell, T Keith / Mizunuma, Masaki

Aging cell

2022 Volume 21, Issue 5, Page(s) e13604

Abstract: Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates ... ...

Abstract	Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates the energy sensor AMP-activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces Met levels and recapitulates many physiological and molecular effects of MetR. In yeast, SAH supplementation leads to inhibition of the target of rapamycin complex 1 (TORC1) and activation of autophagy. Furthermore, in Caenorhabditis elegans SAH treatment extends lifespan by activating AMPK and providing benefits of MetR. Therefore, we propose that SAH can be used as an intervention to lower intracellular Met and confer benefits of MetR.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Aging/metabolism ; Animals ; Longevity ; Methionine/metabolism ; Methionine/pharmacology ; S-Adenosylhomocysteine/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
Chemical Substances	S-Adenosylhomocysteine (979-92-0) ; Methionine (AE28F7PNPL) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2022-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13604
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Zs.A 6581: Show issues

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Article ; Online: TOR Signaling in

Blackwell, T Keith / Sewell, Aileen K / Wu, Ziyun / Han, Min

Genetics

2019 Volume 213, Issue 2, Page(s) 329–360

Abstract: ... ...

Abstract	The
MeSH term(s)	Aging/genetics ; Aging/pathology ; Animals ; Caenorhabditis elegans/genetics ; Humans ; Longevity/genetics ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; Transcription Factors
Chemical Substances	Transcription Factors ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2019-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1534/genetics.119.302504
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Zs.B 767: Show issues

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Article: Oxidative Stress Assays (arsenite and tBHP) in

Ewald, Collin Yvès / Hourihan, John M / Blackwell, T Keith

Bio-protocol

2018 Volume 7, Issue 13

Abstract: Cells and organisms face constant exposure to reactive oxygen species (ROS), either from the environment or as a by-product from internal metabolic processes. To prevent cellular damage from ROS, cells have evolved detoxification mechanisms. The ... ...

Abstract	Cells and organisms face constant exposure to reactive oxygen species (ROS), either from the environment or as a by-product from internal metabolic processes. To prevent cellular damage from ROS, cells have evolved detoxification mechanisms. The activation of these detoxification mechanisms and their downstream responses represent an overlapping defense response that can be tailored to different sources of ROS to adequately adapt and protect cells. In this protocol, we describe how to measure the sensitivity to oxidative stress from two different sources, arsenite and tBHP, using the nematode
Language	English
Publishing date	2018-02-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.2365
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Article ; Online: Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics.

Campos, Juliane Cruz / Marchesi Bozi, Luiz Henrique / Krum, Barbara / Grassmann Bechara, Luiz Roberto / Ferreira, Nikolas Dresch / Arini, Gabriel Santos / Albuquerque, Rudá Prestes / Traa, Annika / Ogawa, Takafumi / van der Bliek, Alexander M / Beheshti, Afshin / Chouchani, Edward T / Van Raamsdonk, Jeremy M / Blackwell, T Keith / Ferreira, Julio Cesar Batista

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 2, Page(s) e2204750120

Abstract: Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and ...

Abstract	Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and fusion are critical effectors of mitochondrial plasticity, which allows a fine-tuned regulation of organelle connectiveness, size, and function. Here we have investigated the role of mitochondrial dynamics during exercise in the model organism
MeSH term(s)	Animals ; Mitochondrial Dynamics/physiology ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Aging/physiology ; Caenorhabditis elegans/metabolism ; Exercise ; Physical Fitness ; Muscle, Skeletal/metabolism
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2023-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2204750120
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Zs.A 1148: Show issues

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Article ; Online: The Implant-borne Articulation Splint in Fibula Free Flap Mandibular Reconstruction: A Technical Note.

Sukato, Daniel C / Kerr, Rhorie / Aghaloo, Tara / Yu, Jason W / Blackwell, Keith E / Jayanetti, Jay

The Journal of craniofacial surgery

2023 Volume 34, Issue 8, Page(s) 2455–2459

Abstract: Computer-aided design and computer-aided manufacturing and digitally simulated surgeries have revolutionized maxillomandibular reconstruction. In particular, this technology has increased the accuracy and facilitated the process of dental implantation in ...

Abstract	Computer-aided design and computer-aided manufacturing and digitally simulated surgeries have revolutionized maxillomandibular reconstruction. In particular, this technology has increased the accuracy and facilitated the process of dental implantation in fibula free flaps. Despite the efficacy of virtual planning, there is a minor degree of translational difference between digital and intraoperative measurements, which may affect the precision of implant and fibula orientations. This is especially concerning during the last stage of fibula insetting, where the graft segments have the potential to roll, yaw, or pitch. The objective of this study is to describe an advanced prosthodontic technique that ensures the fibula grafts and implants remain in a restorable position during final insetting. We describe the technique and workflow of the implant-borne articulation splint through a case presentation and demonstrate results at 4 months postoperative and postradiotherapy. Given the degree of investment placed in virtual planning, free flap reconstruction, and endosteal implants, a technique that ensures optimal restorability of each implant is pivotal. Larger studies are still required to fully elucidate the cost-effectiveness and long-term results of the implant-borne articulation splint.
MeSH term(s)	Humans ; Free Tissue Flaps/surgery ; Dental Implants ; Mandibular Reconstruction/methods ; Fibula/transplantation ; Splints ; Bone Transplantation/methods
Chemical Substances	Dental Implants
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1159501-2
ISSN	1536-3732 ; 1049-2275
ISSN (online)	1536-3732
ISSN	1049-2275
DOI	10.1097/SCS.0000000000009751
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Zs.A 3761: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 175: Show issues

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Article ; Online: Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival.

Chen, Tianzeng / Ho, Matthew / Briere, Jenna / Moscvin, Maria / Czarnecki, Peter G / Anderson, Kenneth C / Blackwell, T Keith / Bianchi, Giada

Blood advances

2021 Volume 6, Issue 2, Page(s) 429–440

Abstract: Multiple myeloma (MM) cells suffer from baseline proteotoxicity as the result of an imbalance between the load of misfolded proteins awaiting proteolysis and the capacity of the ubiquitin-proteasome system to degrade them. This intrinsic vulnerability is ...

Abstract	Multiple myeloma (MM) cells suffer from baseline proteotoxicity as the result of an imbalance between the load of misfolded proteins awaiting proteolysis and the capacity of the ubiquitin-proteasome system to degrade them. This intrinsic vulnerability is at the base of MM sensitivity to agents that perturb proteostasis, such as proteasome inhibitors (PIs), the mainstay of modern-day myeloma therapy. De novo and acquired PI resistance are important clinical limitations that adversely affect prognosis. The molecular mechanisms underpinning PI resistance are only partially understood, limiting the development of drugs that can overcome it. The transcription factor NRF1 is activated by the aspartic protease DNA damage inducible 1 homolog 2 (DDI2) upon proteasome insufficiency and governs proteasome biogenesis. In this article, we show that MM cells exhibit baseline NRF1 activation and are dependent upon DDI2 for survival. DDI2 knockout (KO) is cytotoxic for MM cells, both in vitro and in vivo. Protein structure-function studies show that DDI2 KO blocks NRF1 cleavage and nuclear translocation, causing impaired proteasome activity recovery upon irreversible proteasome inhibition and, thereby, increasing sensitivity to PIs. Add-back of wild-type, but not of catalytically dead DDI2, fully rescues these phenotypes. We propose that DDI2 is an unexplored promising molecular target in MM by disrupting the proteasome stress response and exacerbating proteotoxicity.
MeSH term(s)	Aspartic Acid Proteases/metabolism ; Humans ; Multiple Myeloma ; NF-E2-Related Factor 1/genetics ; NF-E2-Related Factor 1/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/pharmacology ; Proteolysis
Chemical Substances	NF-E2-Related Factor 1 ; NFE2L1 protein, human ; Proteasome Inhibitors ; Aspartic Acid Proteases (EC 3.4.-) ; DDI2 protein, human (EC 3.4.-) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003820
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Zs.A 7153: Show issues

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Article ; Online: Verification of In Vivo Estrogenic Activity for Four Per- and Polyfluoroalkyl Substances (PFAS) Identified as Estrogen Receptor Agonists via New Approach Methodologies.

Villeneuve, Daniel L / Blackwell, Brett R / Cavallin, Jenna E / Collins, Jacob / Hoang, John X / Hofer, Rachel N / Houck, Keith A / Jensen, Kathleen M / Kahl, Michael D / Kutsi, Robin N / Opseth, Anne S / Santana Rodriguez, Kelvin J / Schaupp, Christopher / Stacy, Emma H / Ankley, Gerald T

Environmental science & technology

2023 Volume 57, Issue 9, Page(s) 3794–3803

Abstract: Given concerns about potential toxicological hazards of the thousands of data-poor per- and polyfluorinated alkyl substances (PFAS) currently in commerce and detected in the environment, tiered testing strategies that employ high-throughput in vitro ... ...

Abstract	Given concerns about potential toxicological hazards of the thousands of data-poor per- and polyfluorinated alkyl substances (PFAS) currently in commerce and detected in the environment, tiered testing strategies that employ high-throughput in vitro screening as an initial testing tier have been implemented. The present study evaluated the effectiveness of previous in vitro screening for identifying PFAS capable, or incapable, of inducing estrogenic responses in fish exposed in vivo. Fathead minnows (
MeSH term(s)	Animals ; Estrogens/metabolism ; Fluorocarbons ; Estrone/metabolism ; Cyprinidae ; Alkanesulfonic Acids/metabolism
Chemical Substances	Estrogens ; Fluorocarbons ; ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate ; Estrone (2DI9HA706A) ; Alkanesulfonic Acids
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.2c09315
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Article ; Online: Mild mitochondrial impairment enhances innate immunity and longevity through ATFS-1 and p38 signaling.

Campos, Juliane C / Wu, Ziyun / Rudich, Paige D / Soo, Sonja K / Mistry, Meeta / Ferreira, Julio Cb / Blackwell, T Keith / Van Raamsdonk, Jeremy M

EMBO reports

2021 Volume 22, Issue 12, Page(s) e52964

Abstract: While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted ... ...

Abstract	While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Immunity, Innate/physiology ; Longevity/genetics ; Mitochondria/genetics ; Mitochondria/metabolism ; Signal Transduction
Chemical Substances	Caenorhabditis elegans Proteins
Language	English
Publishing date	2021-10-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202152964
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 41: Show issues

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