{"date_updated":"2026-02-23T10:35:01Z","volume":17,"has_accepted_license":"1","status":"public","scopus_import":"1","publisher":"Elsevier","pmid":1,"issue":"2","PlanS_conform":"1","oa":1,"department":[{"_id":"GradSch"}],"intvolume":"        17","type":"journal_article","day":"18","OA_place":"publisher","abstract":[{"text":"In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus (Pgb1) that modulates hippocampal PGB burden. Extensive transcriptomic and proteomic datasets were produced for the aged hippocampus of the BXD family to investigate the mechanism by which the Pgb1 locus modulates PGB burden. We identified that Pgb1 contains allelic Smarcal1 and Usp37 variants and influences PGB burden through trans-regulation of mRNA and protein expression levels, including abundance of glycogen-mobilizing factor PYGB. Furthermore, comprehensive phenome-wide association scans, transcriptomic analyses, and direct behavioral testing demonstrated that cognition remains intact despite age-related PGB burden. A record of this paper’s transparent peer review process is included in the supplemental information.","lang":"eng"}],"ddc":["570"],"file_date_updated":"2026-02-23T10:32:12Z","citation":{"mla":"Gómez-Pascual, Alicia, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>, vol. 17, no. 2, 101488, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.cels.2025.101488\">10.1016/j.cels.2025.101488</a>.","ieee":"A. Gómez-Pascual <i>et al.</i>, “The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus,” <i>Cell Systems</i>, vol. 17, no. 2. Elsevier, 2026.","ama":"Gómez-Pascual A, Glikman DM, Ng HX, et al. The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. <i>Cell Systems</i>. 2026;17(2). doi:<a href=\"https://doi.org/10.1016/j.cels.2025.101488\">10.1016/j.cels.2025.101488</a>","short":"A. Gómez-Pascual, D.M. Glikman, H.X. Ng, J.E. Tomkins, L. Lu, Y. Xu, D.G. Ashbrook, C. Kaczorowski, G. Kempermann, J. Killmar, K. Mozhui, O. Ohlenschläger, R. Aebersold, D.K. Ingram, E.G. Williams, M. Jucker, R.W. Overall, R.W. Williams, D.E.M. de Bakker, Cell Systems 17 (2026).","apa":"Gómez-Pascual, A., Glikman, D. M., Ng, H. X., Tomkins, J. E., Lu, L., Xu, Y., … de Bakker, D. E. M. (2026). The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2025.101488\">https://doi.org/10.1016/j.cels.2025.101488</a>","chicago":"Gómez-Pascual, Alicia, Dow M Glikman, Hui Xin Ng, James E. Tomkins, Lu Lu, Ying Xu, David G. Ashbrook, et al. “The Smarcal1-Usp37 Locus Modulates Glycogen Aggregation in Astrocytes of the Aged Hippocampus.” <i>Cell Systems</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.cels.2025.101488\">https://doi.org/10.1016/j.cels.2025.101488</a>.","ista":"Gómez-Pascual A, Glikman DM, Ng HX, Tomkins JE, Lu L, Xu Y, Ashbrook DG, Kaczorowski C, Kempermann G, Killmar J, Mozhui K, Ohlenschläger O, Aebersold R, Ingram DK, Williams EG, Jucker M, Overall RW, Williams RW, de Bakker DEM. 2026. The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus. Cell Systems. 17(2), 101488."},"article_processing_charge":"No","oa_version":"Published Version","quality_controlled":"1","author":[{"last_name":"Gómez-Pascual","full_name":"Gómez-Pascual, Alicia","first_name":"Alicia"},{"last_name":"Glikman","id":"ab8acda1-91c1-11f0-aad8-f75d3d6424d8","first_name":"Dow M","full_name":"Glikman, Dow M"},{"last_name":"Ng","first_name":"Hui Xin","full_name":"Ng, Hui Xin"},{"full_name":"Tomkins, James E.","first_name":"James E.","last_name":"Tomkins"},{"full_name":"Lu, Lu","first_name":"Lu","last_name":"Lu"},{"first_name":"Ying","full_name":"Xu, Ying","last_name":"Xu"},{"first_name":"David G.","full_name":"Ashbrook, David G.","last_name":"Ashbrook"},{"first_name":"Catherine","full_name":"Kaczorowski, Catherine","last_name":"Kaczorowski"},{"last_name":"Kempermann","full_name":"Kempermann, Gerd","first_name":"Gerd"},{"full_name":"Killmar, John","first_name":"John","last_name":"Killmar"},{"last_name":"Mozhui","first_name":"Khyobeni","full_name":"Mozhui, Khyobeni"},{"last_name":"Ohlenschläger","first_name":"Oliver","full_name":"Ohlenschläger, Oliver"},{"first_name":"Rudolf","full_name":"Aebersold, Rudolf","last_name":"Aebersold"},{"last_name":"Ingram","full_name":"Ingram, Donald K.","first_name":"Donald K."},{"last_name":"Williams","full_name":"Williams, Evan G.","first_name":"Evan G."},{"first_name":"Mathias","full_name":"Jucker, Mathias","last_name":"Jucker"},{"last_name":"Overall","first_name":"Rupert W.","full_name":"Overall, Rupert W."},{"first_name":"Robert W.","full_name":"Williams, Robert W.","last_name":"Williams"},{"full_name":"de Bakker, Dennis E.M.","first_name":"Dennis E.M.","last_name":"de Bakker"}],"month":"02","article_type":"original","article_number":"101488","date_published":"2026-02-18T00:00:00Z","external_id":{"pmid":["41633365"]},"title":"The Smarcal1-Usp37 locus modulates glycogen aggregation in astrocytes of the aged hippocampus","publication":"Cell Systems","_id":"21234","file":[{"success":1,"date_created":"2026-02-23T10:32:12Z","checksum":"920e8edfd3b8b42f5bb6f86d4c66c54d","content_type":"application/pdf","date_updated":"2026-02-23T10:32:12Z","file_name":"2026_CellSystems_GomezPascual.pdf","relation":"main_file","file_id":"21349","file_size":10606778,"creator":"dernst","access_level":"open_access"}],"date_created":"2026-02-16T10:45:10Z","OA_type":"hybrid","publication_status":"published","doi":"10.1016/j.cels.2025.101488","language":[{"iso":"eng"}],"acknowledgement":"We would like to thank the Summer School Systems Genetics of Neural Ageing for bringing us together and spurring our international collaboration. We would also like to acknowledge the funding for the Summer School 2022 from the e:Med Systems Medicine Program of the BMBF (Bundesministerium für Bildung und Forschung; German Ministry of Education and Research) to R.W.O. In addition, we would like to thank the FLI imaging core facility for their assistance. A.G.-P. is supported by Fundación Séneca, Región de Murcia, Spain (21259/FPI/19). D.E.M.d.B. is financed by a Rubicon scholarship (452021116) from the Dutch Research Council (NWO). This work was also supported by NIH NIA R01AG070913-01 (R.W.W.), R01AG075813-01 (D.G.A.), and R01AG075818 (C.K.). We acknowledge the help of Larry Mobraaten (Jackson Laboratory, Bar Harbor, MN) with the BXD strains and U. Obermüller for the help with the histology. For the purpose of open access, the authors have applied a CC BY public copyright license to all author-accepted manuscripts arising from this submission.","publication_identifier":{"issn":["2405-4712"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"year":"2026","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}