Hallmarks of aging: An expanding universe

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 243 - 278

Published: Jan. 1, 2023

Language: Английский

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹

Autophagy, Journal Year: 2021, Volume and Issue: 17(1), P. 1 - 382

Published: Jan. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Language: Английский

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Lysosomes as dynamic regulators of cell and organismal homeostasis

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 101 - 118

Published: Nov. 25, 2019

Language: Английский

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Autophagy in healthy aging and disease

Nature Aging, Journal Year: 2021, Volume and Issue: 1(8), P. 634 - 650

Published: Aug. 12, 2021

Language: Английский

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The quest to slow ageing through drug discovery

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(8), P. 513 - 532

Published: May 28, 2020

Language: Английский

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Meta-hallmarks of aging and cancer

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(1), P. 12 - 35

Published: Jan. 1, 2023

Language: Английский

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SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 21, 2021

Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated might lead to excessive inflammatory autoimmune responses as observed in severe long COVID-19 patients. Here we show that SARS-CoV-2 modulates reduces Accordingly, compound-driven induction of autophagy limits propagation. In detail, SARS-CoV-2-infected cells accumulation key metabolites, activation inhibitors (AKT1, SKP2) reduction proteins responsible for initiation (AMPK, TSC2, ULK1), membrane nucleation, phagophore formation (BECN1, VPS34, ATG14), well autophagosome-lysosome fusion ATG14 oligomers). Consequently, phagophore-incorporated markers LC3B-II P62 accumulate, which confirm a hamster model lung samples Single-nucleus single-cell sequencing patient-derived mucosal differential transcriptional regulation immune genes depending on cell type, disease duration, replication levels. Targeting autophagic pathways by exogenous administration the polyamines spermidine spermine, selective AKT1 inhibitor MK-2206, BECN1-stabilizing anthelmintic drug niclosamide inhibit propagation vitro with IC

Language: Английский

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Autophagy and the hallmarks of aging

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101468 - 101468

Published: Sept. 24, 2021

Language: Английский

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Biomarkers of aging

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

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Mitochondrial metabolism regulates macrophage biology

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 297(1), P. 100904 - 100904

Published: June 23, 2021

Mitochondria are critical for regulation of the activation, differentiation, and survival macrophages other immune cells. In response to various extracellular signals, such as microbial or viral infection, changes mitochondrial metabolism physiology could underlie corresponding state macrophage activation. These include alterations oxidative metabolism, membrane potential, tricarboxylic acid (TCA) cycling, well release reactive oxygen species (mtROS) DNA (mtDNA) transformation ultrastructure. Here, we provide an updated review how in metabolites fumarate, succinate, itaconate coordinate guide activation distinct cellular states, thus clarifying vital link between mitochondria immunity. We also discuss disease settings, dysfunction stress contribute dysregulation inflammatory response. Therefore, a source dynamic signals that regulate biology fine-tune responses. Macrophages safeguard tissue homeostasis To exert these varied functions, show high plasticity adopt different states according stimulus signals. The Th1 cytokine interferon-γ (IFNγ) together with Toll-like receptor (TLR) ligands, including lipopolysaccharide (LPS), promotes classically activated proinflammatory (commonly known M1-like macrophages), which secrete cytokines interleukin-6 (IL-6) IL-1β induce responses fight against infection; generate highly nitrogen intermediates gain efficient microbicidal tumoricidal activities; increase major histocompatibility complex (MHC)-I/II, CD80, CD86 expression (1Orecchioni M. Ghosheh Y. Pramod A.B. Ley K. Macrophage polarization: Different gene signatures M1(LPS+) vs. M2(LPS-) alternatively macrophages.Front. Immunol. 2019; 10: 1084Crossref PubMed Scopus (239) Google Scholar, 2Shapouri-Moghaddam A. Mohammadian S. Vazini H. Taghadosi Esmaeili S.A. Mardani F. Seifi B. Mohammadi Afshari J.T. Sahebkar plasticity, polarization, function health disease.J. Cell Physiol. 2018; 233: 6425-6440Crossref (843) Scholar). However, continuous excessive may lead sustained inflammation accessory damage (3Sica Mantovani vivo veritas.J. Clin. Invest. 2012; 122: 787-795Crossref (3169) can be by stimulating factors states. For example, Th2 interleukin-4 (IL-4) IL-13 alternative M2-like activation) 4Gordon Martinez F.O. Alternative macrophages: Mechanism functions.Immunity. 2010; 32: 593-604Abstract Full Text PDF (2409) attenuate Th1/M1-driven inflammation, facilitate repair remodeling, Th2-driven pathologies, asthma helminth infections. Such express range specific scavenging molecules, mannose galactose receptors enzymes arginase (5Xue J. Schmidt S.V. Sander Draffehn Krebs W. Quester I. De Nardo D. Gohel T.D. Emde Schmidleithner L. Ganesan Nino-Castro Mallmann M.R. Labzin Theis et al.Transcriptome-based network analysis reveals spectrum model human activation.Immunity. 2014; 40: 274-288Abstract (1022) 6Natoli G. Monticelli activation: Glancing into diversity.Immunity. 175-177Abstract (0) kinds environmental stimuli, populations will change their shift phenotype, allow them actively participate resolution progression (7Mosser D.M. Edwards J.P. Exploring full activation.Nat. Rev. 2008; 8: 958-969Crossref (5333) Recent studies indicate shifts (mtROS), cycle, ultrastructure, potential. drive breaks rewire TCA cycle influencing enzymes, IDH (isocitrate dehydrogenase) SDH (succinate dehydrogenase), resulting elevations citrate respectively. augment glycolysis (also Warburg Effect). contrast, IL-4-activated maintain unbroken preferentially engage phosphorylation (OXPHOS) fatty oxidation (FAO) ATP production. OXPHOS is fueled acids glutamine, activates peroxisome proliferator-activated receptor-γ (PPARγ) mediate induction genes regulating functions (8Batista-Gonzalez Vidal R. Criollo Carreño L.J. New insights on role lipid metabolic reprogramming 2993Crossref (5) Glucose oxidation, induced mTORC2-IRF4 signaling axis, contributes IL-4 mediated (9Huang S.C. Smith A.M. Everts Colonna Pearce E.L. Schilling J.D. E.J. Metabolic axis essential 2016; 45: 817-830Abstract (238) Shifts closely linked this review, mechanistic underpinnings differential they biology. type I usually starts when sentinel cells pathogen-associated molecular patterns (PAMPs), cell wall components, nucleic acids, lipoproteins. undergoes during At center mitochondria, not only supplies energy but involved biosynthesis maintaining redox serves platform innate immunological pathways (10Tur Vico T. Lloberas Zorzano Celada mitochondria: A interplay signaling, functional activity.Adv. 2017; 133: 1-36Crossref (21) alter activity electron transport chain (ETC) influence multiple aspects metabolism. They upregulation glucose glutamine utilization toward anabolic pathways. Aerobic glycolysis, LPS-stimulated mammalian target rapamycin (mTOR) hypoxia-inducible factor 1-alpha (HIF-1α) (11Cheng Quintin Cramer R.A. Shepardson K.M. Saeed Kumar V. Giamarellos-Bourboulis Martens J.H. Rao N.A. Aghajanirefah Manjeri G.R. Li Ifrim D.C. Arts R.J. van der Veer B.M. al.mTOR- HIF-1α-mediated aerobic basis trained immunity.Science. 345: 1250684Crossref (741) Scholar), upregulated production while repressed through mechanisms, two cycle. One break results from decreased IDH, enzyme converts α-ketoglutarate (α-KG), allowing cumulation citrate, redirected generating itaconic withdrawn (12Jha A.K. Huang Sergushichev Lampropoulou Ivanova Loginicheva E. Chmielewski Stewart Ashall Driggers E.M. Artyomov M.N. Network integration parallel transcriptional data modules polarization.Immunity. 2015; 42: 419-430Abstract (737) second occurs after novel pathway termed aspartate-arginosuccinate shunt, produce arginine support nitric oxide (NO) NO generated inducible synthase (iNOS) hamper respiration impair anti-inflammatory repolarization, LPS plus IFNγ stimulation inhibit FAO (13Eisner Picard Hajnóczky Mitochondrial dynamics adaptive maladaptive responses.Nat. Biol. 20: 755-765Crossref (161) Consistently, suppressed LPS-tolerant macrophages, no longer able result long-term exposure (14Butcher S.K. O'Carroll C.E. Wells C.A. Carmody tolerance training restimulation 9: 933Crossref (28) Note some characteristics tolerant resemble M2 it would oversimplification equate differ many have more demand glucose, compared rely β-oxidation. increased necessary engaging derived lipolysis triglycerides (15Huang O'Sullivan Nascimento Beatty Love-Gregory Lam W.Y. O'Neill C.M. Yan C. Du Abumrad Urban Jr., J.F. al.Cell-intrinsic lysosomal macrophages.Nat. 15: 846-855Crossref (528) This adaptation proportion NADH FADH2 (nicotinamide adenine dinucleotide flavin dinucleotide) feeds ETC (16Van den Bossche Baardman Otto Velden Neele A.E. Berg S.M. Luque-Martin Chen H.J. Boshuizen M.C. Ahmed Hoeksema M.A. de Vos A.F. Winther M.P. prevents repolarization macrophages.Cell Rep. 17: 684-696Abstract (262) Inhibition sufficient repress phenotype programs (17Johnson A.R. Qin Cozzo A.J. Freemerman M.J. Zhao Sampey B.P. Milner J.J. Beck Damania Rashid N. Galanko J.A. Lee D.P. Edin M.L. Zeldin al.Metabolic protein 1 (FATP1) regulates potential adipose inflammation.Mol. Metab. 5: 506-526Crossref (58) Similar PAMPs, self-encoded damage-associated (DAMPs) N-formyl peptides (NFP) detected leading (18Dela Cruz C.S. Kang associated chronic diseases.Mitochondrion. 41: 37-44Crossref (53) class DAMPs represented oxidized naturally occurring phospholipids, 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (PAPC) collectively oxPAPC, resides membranes lipoproteins PAMPs optimal (19Freigang phospholipids.Eur. 46: 1818-1825Crossref (39) 20Chu L.H. Indramohan Ratsimandresy Gangopadhyay Morris E.P. Monack Dorfleutner Stehlik phospholipid oxPAPC protects septic shock targeting non-canonical inflammasome Commun. 996Crossref (65) OxPAPC modulates upregulating utilization, anaplerotic carbon replenishes intermediates, cytoplasmic levels oxaloacetate (OAA). HIF-1α key transcription numerous proglycolytic IL-1β, its stability tightly regulated OAA, prolyl hydroxylases (PHDs) (21Koivunen P. Hirsilä Remes Hassinen I.E. Kivirikko K.I. Myllyharju (HIF) citric intermediates: Possible links stabilization HIF.J. Chem. 2007; 282: 4524-4532Abstract (361) treatment stabilizes potentiates presence intact (22Di Gioia Spreafico Springstead J.R. Mendelson M.M. Joehanes Levy Zanoni Endogenous phospholipids reprogram boost hyperinflammation.Nat. 2020; 21: 42-53Crossref (33) been shown powerful roles effects pathways, factors, chromatin (23Novakovic Habibi Wang S.Y. R.J.W. Davar Megchelenbrink Kim Kuznetsova Kox Zwaag Matarese Heeringen S.J. Janssen-Megens Sharifi al.β-Glucan reverses epigenetic LPS-induced tolerance.Cell. 167: 1354-1368.e1314Abstract (206) 24Baardman Licht Van Metabolic-epigenetic crosstalk activation.Epigenomics. 7: 1155-1164Crossref 25Noe Mitchell Tricarboxylic control effector phenotypes.J. Leukoc. 106: 359-367Crossref Because disruptions stimulated LPS, certain itaconate, succinate accumulate play important (Fig. 1). Citrate nuclear-cytosolic pool acetyl coenzyme (Acetyl-CoA), substrate histone acetylation synthesis, both (26Wellen K.E. Hatzivassiliou Sachdeva U.M. Bui T.V. Cross Thompson C.B. ATP-citrate lyase acetylation.Science. 2009; 324: 1076-1080Crossref (1258) 27Covarrubias Aksoylar H.I. Yu Snyder N.W. Worth Iyer S.S. Ben-Sahra Byles Polynne-Stapornkul Espinosa E.C. Lamming Manning B.D. Zhang Blair I.A. al.Akt-mTORC1 Acly integrate input activation.Elife. 5e11612Crossref (196) 28Langston P.K. Nambu Jung Shibata Lei Xu Doan M.T. Jiang MacArthur Gao X. Kong Chouchani E.T. Locasale J.W. al.Glycerol phosphate shuttle GPD2 1186-1195Crossref (37) 29Williams N.C. L.A.J. intermediate immunity inflammation.Front. 141Crossref (150) exported carrier (CIC), followed cleavage acetyl-CoA (ACLY) cytosol. Acetyl-CoA TNFα prostaglandin has fuel at LPS-inducible M1 respectively (27Covarrubias Oxaloacetate needed ROS providing NADPH (30Infantino Pierri C.L. Iacobazzi routes inflammation: therapeutic target.Curr. Med. 26: 7104-7116Crossref (15) addition, acted aconitase 2 (ACO2) cis-aconitate, further decarboxylated synthesis (31Kim Seo H.M. Bhatia Song H.S. Jeon J.M. Choi K.Y. Yoon Y.G. Yang Y.H. Production whole-cell bioconversion cis-aconitate decarboxylase (cadA) Escherichia coli.Sci. 39768Crossref Itaconate acts negative regulator inhibiting (32Lampropoulou Bambouskova Nair Vincent E.E. Cervantes-Barragan Ma Griss Weinheimer C.J. Khader Randolph G.J. Jones R.G. al.Itaconate inhibition dehydrogenase remodeling inflammation.Cell 24: 158-166Abstract findings endow transported crucial via ROS, NO, prostaglandin, (33Infantino Convertini Cucci Panaro Di Noia Calvello Palmieri carrier: new player inflammation.Biochem. 2011; 438: 433-436Crossref (208) 34O'Neill L.A. signalling.Biochem. e5-e6Crossref (64) Scholar) Itaconate, produced matrix metabolite immune-responsive (IRG1) (35Degrandi Hoffmann Beuter-Gunia Pfeffer cytokine-induced IRG1 associates mitochondria.J. Interferon Cytokine Res. 29: 55-67Crossref (60) 36Michelucci Cordes Ghelfi Pailot Reiling Goldmann O. Binz Wegner Tallam Rausell Buttini Linster Medina Balling Hiller Immune-responsive catalyzing production.Proc. Natl. Acad. Sci. U. 2013; 110: 7820-7825Crossref (418) critically growing number reducing 37Mills Ryan D.G. Prag H.A. Dikovskaya Menon Zaslona Z. Jedrychowski Costa A.S.H. Higgins Hams Szpyt Runtsch King M.S. McGouran Fischer Nrf2 alkylation KEAP1.Nature. 556: 113-117Crossref (446) influences suppressing SDH, Complex II ETC. leads accumulation decreases consumption 38O'Neill Itaconate: poster child function.Nat. 19: 273-281Crossref Furthermore, electrophile alkylate cysteine residues KEAP1 (37Mills electrophilic sensor normally drives ubiquitination degradation NF-E2–related (Nrf2) (39Yamamoto Kensler T.W. Motohashi KEAP1-NRF2 system: thiol-based sensor-effector apparatus homeostasis.Physiol. 98: 1169-1203Crossref (386) newly synthesized accumulate, translocate nucleus, initiate antioxidant program. way, actions suggest Nrf2-dependent (40Sun K.A. Meliton A.Y. Woods P.S. Kimmig L.M. Cetin-Atalay Hamanaka R.B. Mutlu G.M. required particulate matter-induced NRF2 response.Elife. 9e54877Crossref (14) reported properties derivatives IκBζ activating 3, selective TLR-inducible (41Bambouskova Gorvel Johnson Korenfeld Mathyer M.E. Duncan Bregman Keskin Santeford Apte R.S. al.Electrophilic IκBζ-ATF3 axis.Nature. 501-504Crossref (202) Finally, there feedback loop interferon signaling. Type interferons enhance Irg1 generation limits repressing cytokines, IL1-β IL6 42Yu X.H. D.W. Zheng X.L. Tang C.K. An emerging determinant macrophages.Immunol. 97: 134-141PubMed It accumulates enhances production, acting signal activate (43Tannahill Curtis Adamik Palsson-McDermott McGettrick Goel Frezza Bernard N.J. Kelly Foley N.H. Gardet Tong Jany Corr al.Succinate induces HIF-1α.Nature. 496: 238-242Crossref (1584) 44Mills Logan Varma Bryant Tourlomousis Däbritz J.H.M. Gottlieb Latorre McManus Jacobs H.T. Szibor supports repurposing macrophages.Cell. 457-470.e413Abstract (681) Succinate (SDH) reverse (RET) PHD inhibition, glycolytic sustaining autocrine called (SUCNR1) enhancing (45Littlewood-Evans Sarret Apfel Loesle Dawson Muller Tigani Kneuer Patel Valeaux Gommermann Rubic-Schneider Junt Carballido GPR91 senses released exacerbates rheumatoid arthritis.J. Exp. 213: 1655-1662Crossref (182) intestinal Tuft gut SUCNR1, microbiota-induced infectious agents (46Murphy reimagined: transducers.Cell. 174: 780-784Abstract Pu

Language: Английский

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