TY - JOUR A1 - Middeldorp, Christel M. A1 - Mahajan, Anubha A1 - Horikoshi, Momoko A1 - Robertson, Neil R. A1 - Beaumont, Robin N. A1 - Bradfield, Jonathan P. A1 - Bustamante, Mariona A1 - Cousminer, Diana L. A1 - Day, Felix R. A1 - De Silva, N. Maneka A1 - Guxens, Monica A1 - Mook-Kanamori, Dennis O. A1 - St Pourcain, Beate A1 - Warrington, Nicole M. A1 - Adair, Linda S. A1 - Ahlqvist, Emma A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Ang, Wei A1 - Atalay, Mustafa A1 - Auvinen, Juha A1 - Bartels, Meike A1 - Beckmann, Jacques S. A1 - Bilbao, Jose Ramon A1 - Bond, Tom A1 - Borja, Judith B. A1 - Cavadino, Alana A1 - Charoen, Pimphen A1 - Chen, Zhanghua A1 - Coin, Lachlan A1 - Cooper, Cyrus A1 - Curtin, John A. A1 - Custovic, Adnan A1 - Das, Shikta A1 - Davies, Gareth E. A1 - Dedoussis, George V. A1 - Duijts, Liesbeth A1 - Eastwood, Peter R. A1 - Eliasen, Anders U. A1 - Elliott, Paul A1 - Eriksson, Johan G. A1 - Estivill, Xavier A1 - Fadista, Joao A1 - Fedko, Iryna O. A1 - Frayling, Timothy M. A1 - Gaillard, Romy A1 - Gauderman, W. James A1 - Geller, Frank A1 - Gilliland, Frank A1 - Gilsanz, Vincente A1 - Granell, Raquel A1 - Grarup, Niels A1 - Groop, Leif A1 - Hadley, Dexter A1 - Hakonarson, Hakon A1 - Hansen, Torben A1 - Hartman, Catharina A. A1 - Hattersley, Andrew T. A1 - Hayes, M. Geoffrey A1 - Hebebrand, Johannes A1 - Heinrich, Joachim A1 - Helgeland, Oyvind A1 - Henders, Anjali K. A1 - Henderson, John A1 - Henriksen, Tine B. A1 - Hirschhorn, Joel N. A1 - Hivert, Marie-France A1 - Hocher, Berthold A1 - Holloway, John W. A1 - Holt, Patrick A1 - Hottenga, Jouke-Jan A1 - Hypponen, Elina A1 - Iniguez, Carmen A1 - Johansson, Stefan A1 - Jugessur, Astanand A1 - Kahonen, Mika A1 - Kalkwarf, Heidi J. A1 - Kaprio, Jaakko A1 - Karhunen, Ville A1 - Kemp, John P. A1 - Kerkhof, Marjan A1 - Koppelman, Gerard H. A1 - Korner, Antje A1 - Kotecha, Sailesh A1 - Kreiner-Moller, Eskil A1 - Kulohoma, Benard A1 - Kumar, Ashish A1 - Kutalik, Zoltan A1 - Lahti, Jari A1 - Lappe, Joan M. A1 - Larsson, Henrik A1 - Lehtimaki, Terho A1 - Lewin, Alexandra M. A1 - Li, Jin A1 - Lichtenstein, Paul A1 - Lindgren, Cecilia M. A1 - Lindi, Virpi A1 - Linneberg, Allan A1 - Liu, Xueping A1 - Liu, Jun A1 - Lowe, William L. A1 - Lundstrom, Sebastian A1 - Lyytikainen, Leo-Pekka A1 - Ma, Ronald C. W. A1 - Mace, Aurelien A1 - Magi, Reedik A1 - Magnus, Per A1 - Mamun, Abdullah A. A1 - Mannikko, Minna A1 - Martin, Nicholas G. A1 - Mbarek, Hamdi A1 - McCarthy, Nina S. A1 - Medland, Sarah E. A1 - Melbye, Mads A1 - Melen, Erik A1 - Mohlke, Karen L. A1 - Monnereau, Claire A1 - Morgen, Camilla S. A1 - Morris, Andrew P. A1 - Murray, Jeffrey C. A1 - Myhre, Ronny A1 - Najman, Jackob M. A1 - Nivard, Michel G. A1 - Nohr, Ellen A. A1 - Nolte, Ilja M. A1 - Ntalla, Ioanna A1 - Oberfield, Sharon E. A1 - Oken, Emily A1 - Oldehinkel, Albertine J. A1 - Pahkala, Katja A1 - Palviainen, Teemu A1 - Panoutsopoulou, Kalliope A1 - Pedersen, Oluf A1 - Pennell, Craig E. A1 - Pershagen, Goran A1 - Pitkanen, Niina A1 - Plomin, Robert A1 - Power, Christine A1 - Prasad, Rashmi B. A1 - Prokopenko, Inga A1 - Pulkkinen, Lea A1 - Raikkonen, Katri A1 - Raitakari, Olli T. A1 - Reynolds, Rebecca M. A1 - Richmond, Rebecca C. A1 - Rivadeneira, Fernando A1 - Rodriguez, Alina A1 - Rose, Richard J. A1 - Salem, Rany A1 - Santa-Marina, Loreto A1 - Saw, Seang-Mei A1 - Schnurr, Theresia M. A1 - Scott, James G. A1 - Selzam, Saskia A1 - Shepherd, John A. A1 - Simpson, Angela A1 - Skotte, Line A1 - Sleiman, Patrick M. A. A1 - Snieder, Harold A1 - Sorensen, Thorkild I. A. A1 - Standl, Marie A1 - Steegers, Eric A. P. A1 - Strachan, David P. A1 - Straker, Leon A1 - Strandberg, Timo A1 - Taylor, Michelle A1 - Teo, Yik-Ying A1 - Thiering, Elisabeth A1 - Torrent, Maties A1 - Tyrrell, Jessica A1 - Uitterlinden, Andre G. A1 - van Beijsterveldt, Toos A1 - van der Most, Peter J. A1 - van Duijn, Cornelia M. A1 - Viikari, Jorma A1 - Vilor-Tejedor, Natalia A1 - Vogelezang, Suzanne A1 - Vonk, Judith M. A1 - Vrijkotte, Tanja G. M. A1 - Vuoksimaa, Eero A1 - Wang, Carol A. A1 - Watkins, William J. A1 - Wichmann, H-Erich A1 - Willemsen, Gonneke A1 - Williams, Gail M. A1 - Wilson, James F. A1 - Wray, Naomi R. A1 - Xu, Shujing A1 - Xu, Cheng-Jian A1 - Yaghootkar, Hanieh A1 - Yi, Lu A1 - Zafarmand, Mohammad Hadi A1 - Zeggini, Eleftheria A1 - Zemel, Babette S. A1 - Hinney, Anke A1 - Lakka, Timo A. A1 - Whitehouse, Andrew J. O. A1 - Sunyer, Jordi A1 - Widen, Elisabeth E. A1 - Feenstra, Bjarke A1 - Sebert, Sylvain A1 - Jacobsson, Bo A1 - Njolstad, Pal R. A1 - Stoltenberg, Camilla A1 - Smith, George Davey A1 - Lawlor, Debbie A. A1 - Paternoster, Lavinia A1 - Timpson, Nicholas J. A1 - Ong, Ken K. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Jaddoe, Vincent W. V. A1 - Tiemeier, Henning A1 - Jarvelin, Marjo-Riitta A1 - Evans, David M. A1 - Perry, John R. B. A1 - Grant, Struan F. A. A1 - Boomsma, Dorret I. A1 - Freathy, Rachel M. A1 - McCarthy, Mark I. A1 - Felix, Janine F. T1 - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia BT - design, results and future prospects JF - European journal of epidemiology N2 - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites. KW - Genetics KW - Consortium KW - Childhood traits and disorders KW - Longitudinal Y1 - 2019 U6 - https://doi.org/10.1007/s10654-019-00502-9 SN - 0393-2990 SN - 1573-7284 VL - 34 IS - 3 SP - 279 EP - 300 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Elias-Miro, Maria A1 - Massip-Salcedo, Marta A1 - Raila, Jens A1 - Schweigert, Florian J. A1 - Mendes-Braz, Mariana A1 - Ramalho, Fernando A1 - Jimenez-Castro, Monica B. A1 - Casillas-Ramirez, Arani A1 - Bermudo, Raquel A1 - Rimola, Antoni A1 - Rodes, Juan A1 - Peralta, Carmen T1 - Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion JF - Liver transplantation N2 - Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198-1208, 2012. Y1 - 2012 U6 - https://doi.org/10.1002/lt.23489 SN - 1527-6465 VL - 18 IS - 10 SP - 1198 EP - 1208 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Castro, Jose Pedro A1 - Fernando, Raquel A1 - Reeg, Sandra A1 - Meinl, Walter A1 - Almeida, Henrique A1 - Grune, Tilman T1 - Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation BT - A novel gain-of-function mechanism JF - Redox Biology N2 - Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins. KW - Oxidative stress KW - Protein oxidation KW - Heat shock protein 90 KW - Proteasome KW - Protein aggregates Y1 - 2019 U6 - https://doi.org/10.1016/j.redox.2019.101108 SN - 2213-2317 VL - 21 PB - Elsevier CY - Amsterdam ER - TY - THES A1 - Lopes Fernando, Raquel Sofia T1 - The impact of aging on proteolytic systems, transcriptome and metabolome of slow and fast muscle fiber types N2 - Aging is a complex process characterized by several factors, including loss of genetic and epigenetic information, accumulation of chronic oxidative stress, protein damage and aggregates and it is becoming an emergent drug target. Therefore, it is the utmost importance to study aging and agerelated diseases, to provide treatments to develop a healthy aging process. Skeletal muscle is one of the earliest tissues affected by age-related changes with progressive loss of muscle mass and function from 30 years old, effect known as sarcopenia. Several studies have shown the accumulation of protein aggregates in different animal models, as well as in humans, suggesting impaired proteostasis, a hallmark of aging, especially regarding degradation systems. Thus, different publications have explored the role of the main proteolytic systems in skeletal muscle from rodents and humans, like ubiquitin proteasomal system (UPS) and autophagy lysosomal system (ALS), however with contradictory results. Yet, most of the published studies are performed in muscles that comprise more than one fiber type, that means, muscles composed by slow and fast fibers. These fiber types, exhibit different metabolism and contraction speed; the slow fibers or type I display an oxidative metabolism, while fast fibers function towards a glycolytic metabolism ranging from fast oxidative to fast glycolytic fibers. To this extent, the aim of this thesis sought to understand on how aging impacts both fiber types not only regarding proteostasis but also at a metabolome and transcriptome network levels. Therefore, the first part of this thesis, presents the differences between slow oxidative (from Soleus muscle) and fast glycolytic fibers (Extensor digitorum longus, EDL) in terms of degradation systems and how they cope with oxidative stress during aging, while the second part explores the differences between young and old EDL muscle transcriptome and metabolome, unraveling molecular features. More specifically, the results from the present work show that slow oxidative muscle performs better at maintaining the function of UPS and ALS during aging than EDL muscle, which is clearly affected, accounting for the decline in the catalytic activity rates and accumulation of autophagy-related proteins. Strinkingly, transcriptome and metabolome analyses reveal that fast glycolytic muscle evidences significant downregulation of mitochondrial related processes and damaged mitochondria morphology during aging, despite of having a lower oxidative metabolism compared to oxidative fibers. Moreover, predictive analyses reveal a negative association between aged EDL gene signature and lifespan extending interventions such as caloric restriction (CR). Although, CR intervention does not alter the levels of mitochondrial markers in aged EDL muscle, it can reverse the higher mRNA levels of muscle damage markers. Together, the results from this thesis give new insights about how different metabolic muscle fibers cope with age-related changes and why fast glycolytic fibers are more susceptible to aging than slow oxidative fibers. N2 - Altern ist ein komplexer Prozess, der durch mehrere Faktoren gekennzeichnet ist, darunter der Verlust genetischer und epigenetischer Informationen, oxidativer Stress, sowie die Anhäufung von Proteinschäden und Aggregaten. Daher ist es von größter Bedeutung, das Altern und altersbedingte Krankheiten zu erforschen, um Arzneimittel und andere Behandlungen für einen gesunden Alterungsprozess zu entwickeln. Die Skelettmuskulatur ist eines der ersten Gewebe, das von altersbedingten Veränderungen betroffen ist. Ab einem Alter von 30 Jahren kommt es zu einem fortschreitenden Verlust der Muskelmasse und -funktion, der auch als Sarkopenie bezeichnet wird. Mehrere Studien haben die Anhäufung von Proteinaggregaten beim Altern in verschiedenen Tiermodellen und auch beim Menschen gezeigt, was auf eine gestörte Proteostase, insbesondere hinsichtlich der Abbauprozesse schließen lässt. Demnach wurde weiterführend die Rolle der wichtigsten proteolytischen Systeme, das Ubiquitin Proteasom System (UPS) und AutophagieLysosomale System (ALS), im alternden Skelettmuskel von Nagetieren und Menschen untersucht. Die Ergebnisse waren widersprüchlich, jedoch wurden die meisten der veröffentlichten Studien an Muskeln durchgeführt, die aus mehr als einem Muskelfasertyp bestehen, d.h. Muskeln, die aus langsamen und schnellen Muskelfasern zusammengesetzt sind. Diese Muskelfasertypen unterscheiden sich hinsichtlich des Stoffwechsels und der Kontraktionsgeschwindigkeit. Die langsamen Fasern oder der Typ I haben einen oxidativen Stoffwechsel, während die schnellen Fasern einen glykolytischen Stoffwechsel aufweisen und aus schnellen oxidativen bis zu schnellen glykolytischen Fasern bestehen können. Insofern war es das Ziel dieser Arbeit zu verstehen, wie sich das Altern auf beide Fasertypen auswirkt, und zwar nicht nur im Hinblick auf die Proteostase, sondern auch auf das Metabolom und Transkriptom. Im ersten Teil dieser Arbeit werden die Unterschiede zwischen langsamen oxidativen (Soleus-Muskel) und schnellen glykolytischen Fasern (Extensor digitorum longus-Muskel; EDL) in Bezug auf die Proteinabbausysteme und die Art und Weise, wie sie mit oxidativem Stress während des Alterns umgehen, dargestellt. Im zweiten Teil werden die Unterschiede zwischen dem Transkriptom und dem Metabolom des jungen und alten EDL-Muskels untersucht, um die molekularen Merkmale zu entschlüsseln. Im Einzelnen zeigen die Ergebnisse der vorliegenden Arbeit, dass der langsam oxidierende Muskel im Vergleich zum EDL-Muskel besser in der Lage ist, die Funktion von UPS und ALS während des Alterns aufrechtzuerhalten. Die Funktionalität des UPS und ALS ist im alternden EDL-Muskels vermindert, was durch den Rückgang der katalytischen Aktivitätsraten und die Anhäufung von mit Autophagie-assoziierten Proteinen gezeigt wurde. Transkriptom- und Metabolomanalysen zeigen, dass schnelle glykolytische Muskeln eine signifikante Herabregulierung mitochondrialer Prozesse und eine geschädigte Mitochondrienmorphologie während des Alterns aufweisen, obwohl sie im Vergleich zu oxidativen Fasern durch einen geringeren oxidativen Stoffwechsel charakterisiert sind. Darüber hinaus ergeben prädiktive Analysen einen negativen Zusammenhang zwischen der Gensignatur des gealterten EDL-Muskels und lebensverlängernden Maßnahmen wie der kalorischenRestriktion. Obwohl die kalorischen Restriktion Intervention die Werte der mitochondrialen Marker im gealterten EDL-Muskel nicht verändert, kann sie die höheren mRNA-Werte der Muskelschädigungsmarker umkehren. Zusammenfassend liefern die Ergebnisse dieser Arbeit neue Erkenntnisse darüber, wie verschiedene metabolische Muskelfasern mit altersbedingten. Veränderungen umgehen und warum schnelle glykolytische Fasern anfälliger für die Alterung als langsame oxidative Fasern sind. KW - skeletal muscle aging KW - proteostasis KW - slow and fast fiber types KW - transcriptomics KW - metabolomics KW - sarcopenia KW - Skelettmuskelalterung KW - Proteostase KW - langsame und schnelle Fasertypen KW - Transkriptom KW - Metabolom KW - ubiquitin proteasomal system KW - autophagy lysosomal system KW - Ubiquitin Proteasom System KW - Autophagie Lysosomale System Y1 - 2023 U6 - https://doi.org/10.25932/publishup-60579 ER - TY - JOUR A1 - Fernando, Raquel A1 - Drescher, Cathleen A1 - Nowotny, Kerstin A1 - Grune, Tilman A1 - Castro, Jose Pedro T1 - Impaired proteostasis during skeletal muscle aging JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research N2 - Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance. KW - Skeletal muscle KW - Proteostasis KW - Proteasome and lysosome KW - Oxidative stress KW - Redox regulation KW - Aging Y1 - 2018 U6 - https://doi.org/10.1016/j.freeradbiomed.2018.08.037 SN - 0891-5849 SN - 1873-4596 VL - 132 SP - 58 EP - 66 PB - Elsevier CY - New York ER - TY - GEN A1 - Fernando, Raquel A1 - Drescher, Cathleen A1 - Deubel, Stefanie A1 - Grune, Tilman A1 - Castro, Jose Pedro T1 - Distinct proteasomal activity for fast and slow twitch skeletal muscle during aging T2 - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research N2 - Skeletal muscle alterations during aging lead to dysfunctional metabolism, correlating with frailty and early mortality. The loss of proteostasis is a hallmark of aging. Whether proteostasis loss plays a role in muscle aging remains elusive. To address this question we collected muscles, Soleus (SOL, type I) and Extensor digitorum longus (EDL, type II), from young (4 months) and old (25 months) C57BL/6 mice and evaluated the proteasomal system. Initial work showed decreased 26 S activity in old SOL. EDL displayed lower proteasomal activity in both ages compared to any of the SOL ages. Moreover, in order to understand if during aging there is the so-called “fiber switch from fast-to-slow”, we performed western blots against sMHC and fMHC (slow and fast myosin heavy chain, respectively). Preliminary results suggest that young SOL is composed by slow twitch fibers but also contains fast twitch fibers, while young EDL seems to be mostly composed by fast twitch fibers that level down during aging, suggesting the switch. As a conclusion, EDL seems to have less proteasomal activity, however, if this is a contributor or a consequence to the muscle fiber switch during aging still needs further investigation. Y1 - 2018 U6 - https://doi.org/10.1016/j.freeradbiomed.2018.04.393 SN - 0891-5849 SN - 1873-4596 VL - 120 SP - S119 EP - S119 PB - Elsevier CY - New York ER - TY - JOUR A1 - Fernando, Raquel A1 - Drescher, Cathleen A1 - Deubel, Stefanie A1 - Jung, Tobias A1 - Ost, Mario A1 - Klaus, Susanne A1 - Grune, Tilman A1 - Castro, Jose Pedro T1 - Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage JF - Experimental gerontology N2 - The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characterized the proteasomal system in two different fiber types, using a non-sarcopenic aging model. By analyzing the proteasomal activity and amount, as well as the polyubiquitinated proteins and the level of protein oxidation in Musculus soleus (Sol) and Musculus extensor digitorum longus (EDL), we found that the slow twitch Sol muscle shows an overall higher respiratory and proteasomal activity in young and old animals. However, especially during aging the fast twitch EDL muscle reduces protein oxidation by an increase of antioxidant capacity. Thus, under adaptive non-sarcopenic conditions, the two fibers types seem to have different strategies to avoid age-related changes. KW - Proteasomal system KW - Skeletal muscle KW - Fast and slow fibers KW - Polyubiquitination KW - Oxidized proteins KW - Antioxidants KW - Aging KW - Mitochondrial respiration Y1 - 2018 U6 - https://doi.org/10.1016/j.exger.2018.10.018 SN - 0531-5565 SN - 1873-6815 VL - 117 SP - 45 EP - 52 PB - Elsevier CY - Oxford ER -