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A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment

Author

Listed:
  • Raúl F. Pérez

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Patricia Tezanos

    (Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC)
    Universidad Autónoma de Madrid-Instituto Cajal)

  • Alfonso Peñarroya

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo)

  • Alejandro González-Ramón

    (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC))

  • Rocío G. Urdinguio

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Javier Gancedo-Verdejo

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Juan Ramón Tejedor

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Pablo Santamarina-Ojeda

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Juan José Alba-Linares

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Lidia Sainz-Ledo

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo)

  • Annalisa Roberti

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo)

  • Virginia López

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Cristina Mangas

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo)

  • María Moro

    (Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC))

  • Elisa Cintado Reyes

    (Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC)
    Universidad Autónoma de Madrid-Instituto Cajal)

  • Pablo Muela Martínez

    (Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC)
    Universidad Autónoma de Madrid-Instituto Cajal)

  • Mar Rodríguez-Santamaría

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo)

  • Ignacio Ortea

    (Universidad de Oviedo
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA-FINBA))

  • Ramón Iglesias-Rey

    (Health Research Institute of Santiago de Compostela (IDIS))

  • Juan Castilla-Silgado

    (Universidad de Oviedo
    Universidad de Oviedo)

  • Cristina Tomás-Zapico

    (Universidad de Oviedo
    Universidad de Oviedo)

  • Eduardo Iglesias-Gutiérrez

    (Universidad de Oviedo
    Universidad de Oviedo)

  • Benjamín Fernández-García

    (Universidad de Oviedo
    Universidad de Oviedo)

  • Jose Vicente Sanchez-Mut

    (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC))

  • José Luis Trejo

    (Instituto Cajal-Consejo Superior de Investigaciones Científicas (IC-CSIC))

  • Agustín F. Fernández

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

  • Mario F. Fraga

    (Universidad de Oviedo
    Universidad de Oviedo
    Universidad de Oviedo
    Instituto de Salud Carlos III (ISCIII))

Abstract

Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.

Suggested Citation

  • Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49608-z
    DOI: 10.1038/s41467-024-49608-z
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    as
    1. David U. Gorkin & Iros Barozzi & Yuan Zhao & Yanxiao Zhang & Hui Huang & Ah Young Lee & Bin Li & Joshua Chiou & Andre Wildberg & Bo Ding & Bo Zhang & Mengchi Wang & J. Seth Strattan & Jean M. Davidson, 2020. "An atlas of dynamic chromatin landscapes in mouse fetal development," Nature, Nature, vol. 583(7818), pages 744-751, July.
    2. Lawrence Hubert & Phipps Arabie, 1985. "Comparing partitions," Journal of Classification, Springer;The Classification Society, vol. 2(1), pages 193-218, December.
    3. Tie-Yuan Zhang & Christopher L. Keown & Xianglan Wen & Junhao Li & Dulcie A. Vousden & Christoph Anacker & Urvashi Bhattacharyya & Richard Ryan & Josie Diorio & Nicholas O’Toole & Jason P. Lerch & Era, 2018. "Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    4. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    5. David U. Gorkin & Iros Barozzi & Yuan Zhao & Yanxiao Zhang & Hui Huang & Ah Young Lee & Bin Li & Joshua Chiou & Andre Wildberg & Bo Ding & Bo Zhang & Mengchi Wang & J. Seth Strattan & Jean M. Davidson, 2020. "Author Correction: An atlas of dynamic chromatin landscapes in mouse fetal development," Nature, Nature, vol. 586(7831), pages 31-31, October.
    6. Toby Mathieson & Holger Franken & Jan Kosinski & Nils Kurzawa & Nico Zinn & Gavain Sweetman & Daniel Poeckel & Vikram S. Ratnu & Maike Schramm & Isabelle Becher & Michael Steidel & Kyung-Min Noh & Gio, 2018. "Systematic analysis of protein turnover in primary cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    7. Sara Zocher & Rupert W. Overall & Mathias Lesche & Andreas Dahl & Gerd Kempermann, 2021. "Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    8. Xiao-Ru Ma & Xudong Zhu & Yujie Xiao & Hui-Min Gu & Shuang-Shuang Zheng & Liang Li & Fan Wang & Zhao-Jun Dong & Di-Xian Wang & Yang Wu & Chenyu Yang & Wenhong Jiang & Ke Yao & Yue Yin & Yang Zhang & C, 2022. "Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Xuran Wang & Jihwan Park & Katalin Susztak & Nancy R. Zhang & Mingyao Li, 2019. "Bulk tissue cell type deconvolution with multi-subject single-cell expression reference," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    10. Giacomo Cavalli & Edith Heard, 2019. "Advances in epigenetics link genetics to the environment and disease," Nature, Nature, vol. 571(7766), pages 489-499, July.
    11. D. D. Han & J. H. Qian & Y. G. Ma, 2011. "Emergence of double scaling law in complex system," Papers 1103.2001, arXiv.org.
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