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Aging

  • Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis
    Open Access
    Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis

    Arun Pal, Benedikt Kretner, Masin Abo-Rady, Hannes Glaβ, Banaja P Dash, Marcel Naumann, Julia Japtok, Nicole Kreiter, Ashutosh Dhingra, Peter Heutink, Tobias M Böckers, René Günther, Jared Sterneckert, Andreas Hermann

    Arun Pal ... Andreas Hermann

    Published 22 February 2021

    Axonal trafficking deficits and neurodegeneration in C9ORF72 motoneurons are mediated by GOF and LOF mechanisms with RNA foci and DPRs as upstream events, whereas DNA damage appears downstream.

  • Reduced RNA turnover as a driver of cellular senescence
    Open Access
    Reduced RNA turnover as a driver of cellular senescence

    Nowsheen Mullani, Yevheniia Porozhan, Adèle Mangelinck, Christophe Rachez, Mickael Costallat, Eric Batsché, Michele Goodhardt, Giovanni Cenci, Carl Mann, Christian Muchardt

    Nowsheen Mullani ... Christian Muchardt

    Published 14 January 2021

    RNAs originating from transcription upstream and downstream of genes accumulate in the cytoplasm of a subset of senescent cells, suggesting an RNA alternative to cytoplasmic DNA in the triggering of senescence.

  • PGE<sub>2</sub> accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking
    Open Access
    PGE2 accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking

    Loka R Penke, Jennifer M Speth, Christina Draijer, Zbigniew Zaslona, Judy Chen, Peter Mancuso, Christine M Freeman, Jeffrey L Curtis, Daniel R Goldstein, Marc Peters-Golden

    Loka R Penke ... Marc Peters-Golden

    Published 20 August 2020

    Dysregulation of self-renewal contributes to alterations in alveolar macrophages (AMs). In this study, Penke et al identify PGE2 as a suppressor of AM proliferation, whose divergent bioavailability in aged and cigarette smoke-exposed mice could explain opposite effects on AM numbers.

  • Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
    Open Access
    Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality

    Mun-Gwan Hong, Tea Dodig-Crnković, Xu Chen, Kimi Drobin, Woojoo Lee, Yunzhang Wang, Fredrik Edfors, David Kotol, Cecilia Engel Thomas, Ronald Sjöberg, Jacob Odeberg, Anders Hamsten, Angela Silveira, Per Hall, Peter Nilsson, Yudi Pawitan, Mathias Uhlén, Nancy L Pedersen, Sara Hägg, Patrik KE Magnusson, Jochen M Schwenk

    Mun-Gwan Hong ... Jochen M Schwenk

    Published 31 July 2020

    Affinity-based proteomics assays identify particular profiles of the circulating histidine-rich glycoprotein to increase with age and elevated levels to indicate a higher risk of all-cause mortality.

  • USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation
    Open Access
    USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation

    Emma V Rusilowicz-Jones, Jane Jardine, Andreas Kallinos, Adan Pinto-Fernandez, Franziska Guenther, Mariacarmela Giurrandino, Francesco G Barone, Katy McCarron, Christopher J Burke, Alejandro Murad, Aitor Martinez, Elena Marcassa, Malte Gersch, Alexandre J Buckmelter, Katherine J Kayser-Bricker, Frederic Lamoliatte, Akshada Gajbhiye, Simon Davis, Hannah C Scott, Emma Murphy, Katherine England, Heather Mortiboys, David Komander, Matthias Trost, Benedikt M Kessler, Stephanos Ioannidis, Michael K Ahlijanian, Sylvie Urbé, Michael J Clague

    Emma V Rusilowicz-Jones ... Michael J Clague

    Published 7 July 2020

    A new inhibitor of the deubiquitylase USP30, an actionable target relevant to Parkinson’s Disease, is introduced and characterised for parameters related to mitophagy.

  • <em>Cx3cr1-</em>deficient microglia exhibit a premature aging transcriptome
    Open Access
    Cx3cr1-deficient microglia exhibit a premature aging transcriptome

    Stefka Gyoneva, Raghavendra Hosur, David Gosselin, Baohong Zhang, Zhengyu Ouyang, Anne C Cotleur, Michael Peterson, Norm Allaire, Ravi Challa, Patrick Cullen, Chris Roberts, Kelly Miao, Taylor L Reynolds, Christopher K Glass, Linda Burkly, Richard M Ransohoff

    Stefka Gyoneva ... Richard M Ransohoff

    Published 2 December 2019

    Gyoneva et al use RNA-seq to show that Cx3cr1-deficient microglia in young mice display a gene expression profile similar to microglia in aged mice, suggesting premature microglial aging.

  • Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications
    Open Access
    Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications

    Shengya Tian, Junru Feng, Yang Cao, Shengqi Shen, Yongping Cai, Dongdong Yang, Ronghui Yan, Lihua Wang, Huafeng Zhang, Xiuying Zhong, Ping Gao

    Shengya Tian ... Ping Gao

    Published 27 September 2019

    The glycine cleavage system (GCS) is highly activated to promote stem cell pluripotency. The GCS catabolizes glycine to prevent methylglyoxal accumulation and to fuel H3K4me3 modification, promoting the expression of pluripotency genes.

  • Dietary restriction induces posttranscriptional regulation of longevity genes
    Open Access
    Dietary restriction induces posttranscriptional regulation of longevity genes

    Jarod A Rollins, Dan Shaffer, Santina S Snow, Pankaj Kapahi, Aric N Rogers

    Jarod A Rollins ... Aric N Rogers

    Published 28 June 2019

    By modulating posttranscriptional processes, including RNA editing, miRNA biogenesis, and intron retention, dietary restriction enacts some of its pro-longevity benefits in Caenorhabditis elegans through posttranscriptional regulation of gene expression.

  • Opposing Roles of apolipoprotein E in aging and neurodegeneration
    Open Access
    Opposing Roles of apolipoprotein E in aging and neurodegeneration

    Eloise Hudry, Jacob Klickstein, Claudia Cannavo, Rosemary Jackson, Alona Muzikansky, Sheetal Gandhi, David Urick, Taylie Sargent, Lauren Wrobleski, Allyson D Roe, Steven S Hou, Kishore V Kuchibhotla, Rebecca A Betensky, Tara Spires-Jones, Bradley T Hyman

    Eloise Hudry ... Bradley T Hyman

    Published 13 February 2019

    This study investigates how APOE modulates neuronal function integrity during normal aging and in the context of amyloidosis. This work demonstrates that APOE is a necessary partner of Aβ-dependent neuronal dysfunction and synaptotoxicity but also preserves neuronal network during aging.

  • <span class="sc">d</span>-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species
    Open Access
    d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species

    Taiki Nagano, Shunsuke Yamao, Anju Terachi, Hidetora Yarimizu, Haruki Itoh, Ryoko Katasho, Kosuke Kawai, Akio Nakashima, Tetsushi Iwasaki, Ushio Kikkawa, Shinji Kamada

    Taiki Nagano ... Shinji Kamada

    Published 18 January 2019

    This study reveals a novel role of d-amino acid oxidase in promoting cellular senescence induced by genotoxic stresses via enzymatic generation of reactive oxygen species.

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