Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice

Kan Xie, Helmut Fuchs, Enzo Scifo, Dan Liu, Ahmad Aziz, Juan Antonio Aguilar-Pimentel, Oana Veronica Amarie, Lore Becker, Patricia da Silva-Buttkus, Julia Calzada-Wack, Yi-Li Cho, Yushuang Deng, A. Cole Edwards, Lillian Garrett, Christina Georgopoulou, Raffaele Gerlini, Sabine M. Hölter, Tanja Klein-Rodewald, Michael Kramer, Stefanie Leuchtenberger, Dimitra Lountzi, Phillip Mayer-Kuckuk, Lena L. Nover, Manuela A. Oestereicher, Clemens Overkott, Brandon L. Pearson, Birgit Rathkolb, Jan Rozman, Jenny Russ, Kristina Schaaf, Nadine Spielmann, Adrián Sanz-Moreno, Claudia Stoeger, Irina Treise, Daniele Bano, Dirk H. Busch, Jochen Graw, Martin Klingenspor, Thomas Klopstock, Beverly A. Mock, Paolo Salomoni, Carsten Schmidt-Weber, Marco Weiergräber, Eckhard Wolf, Wolfgang Wurst, Valérie Gailus-Durner, Monique M. B. Breteler, Martin Hrabě de Angelis and Dan Ehninger ()
Additional contact information
Kan Xie: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Helmut Fuchs: German Research Center for Environmental Health
Enzo Scifo: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Dan Liu: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
Ahmad Aziz: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
Juan Antonio Aguilar-Pimentel: German Research Center for Environmental Health
Oana Veronica Amarie: German Research Center for Environmental Health
Lore Becker: German Research Center for Environmental Health
Patricia da Silva-Buttkus: German Research Center for Environmental Health
Julia Calzada-Wack: German Research Center for Environmental Health
Yi-Li Cho: German Research Center for Environmental Health
Yushuang Deng: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
A. Cole Edwards: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Lillian Garrett: German Research Center for Environmental Health
Christina Georgopoulou: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Raffaele Gerlini: German Research Center for Environmental Health
Sabine M. Hölter: German Research Center for Environmental Health
Tanja Klein-Rodewald: German Research Center for Environmental Health
Michael Kramer: GEMoaB GmbH
Stefanie Leuchtenberger: German Research Center for Environmental Health
Dimitra Lountzi: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Phillip Mayer-Kuckuk: German Research Center for Environmental Health
Lena L. Nover: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Manuela A. Oestereicher: German Research Center for Environmental Health
Clemens Overkott: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Brandon L. Pearson: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Birgit Rathkolb: German Research Center for Environmental Health
Jan Rozman: German Research Center for Environmental Health
Jenny Russ: Nuclear Function Lab, German Center for Neurodegenerative Diseases (DZNE)
Kristina Schaaf: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)
Nadine Spielmann: German Research Center for Environmental Health
Adrián Sanz-Moreno: German Research Center for Environmental Health
Claudia Stoeger: German Research Center for Environmental Health
Irina Treise: German Research Center for Environmental Health
Daniele Bano: Aging and Neurodegeneration Lab, German Center for Neurodegenerative Diseases (DZNE)
Dirk H. Busch: Technische Universität München
Jochen Graw: German Research Center for Environmental Health
Martin Klingenspor: Technische Universität München
Thomas Klopstock: Ludwig-Maximilians-University Munich
Beverly A. Mock: Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH
Paolo Salomoni: Nuclear Function Lab, German Center for Neurodegenerative Diseases (DZNE)
Carsten Schmidt-Weber: Center of Allergy & Environment (ZAUM), Technische Universität München, and Helmholtz Zentrum München
Marco Weiergräber: Research Group Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices
Eckhard Wolf: Ludwig-Maximilians-University Munich
Wolfgang Wurst: German Research Center for Environmental Health
Valérie Gailus-Durner: German Research Center for Environmental Health
Monique M. B. Breteler: Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE)
Martin Hrabě de Angelis: German Research Center for Environmental Health
Dan Ehninger: Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE)

Nature Communications, 2022, vol. 13, issue 1, 1-29

Abstract: Abstract Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions; PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging.

Date: 2022
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DOI: 10.1038/s41467-022-34515-y

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