Choroid plexus-mediated CSF secretion remains stable in aging rats via high and age-resistant metabolic activity

Sara D. Lolansen, Eszter O. Révész, Søren N. Andreassen, Marleen Trapp, Chiara Salio, Marco Sassoé-Pognetto, Jens Velde Andersen, Emil W. Westi, Trine L. Toft-Bertelsen, Jonathan H. Wardman, Anne-Kristine Meinild Lundby, Flemming Dela, Annarita Patrizi, Blanca I. Aldana and Nanna MacAulay ()
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Sara D. Lolansen: University of Copenhagen
Eszter O. Révész: University of Copenhagen
Søren N. Andreassen: University of Copenhagen
Marleen Trapp: German Cancer Research Center (DKFZ)
Chiara Salio: University of Turin
Marco Sassoé-Pognetto: University of Turin
Jens Velde Andersen: University of Copenhagen
Emil W. Westi: University of Copenhagen
Trine L. Toft-Bertelsen: University of Copenhagen
Jonathan H. Wardman: University of Copenhagen
Anne-Kristine Meinild Lundby: University of Copenhagen
Flemming Dela: University of Copenhagen
Annarita Patrizi: German Cancer Research Center (DKFZ)
Blanca I. Aldana: University of Copenhagen
Nanna MacAulay: University of Copenhagen

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Our brain is bathed in cerebrospinal fluid (CSF) that is produced by the choroid plexus. CSF serves as a dispersion route for hormones and nutrients, and a conduit for waste clearance. Age-dependent reduction in the CSF secretion rate could influence cerebral waste clearance and thereby promote cognitive deficits in the elderly. Here, we resolve age-dependent modulation of CSF dynamics and choroid plexus function by complementary in vivo determinations of intracranial pressure (ICP) and CSF secretion/absorption rates, combined with transcriptomic, morphological, and metabolic analysis of choroid plexus in aging male rats. ICP and CSF secretion rate and absorption capacity remain stable with age, and the choroid plexus retains its morphology, structural integrity, gene expression, and high metabolic rate across the tested ages. This work supports the significance of choroid plexus function for brain aging and promotes this tissue as a future target for neurodegenerative diseases associated with impaired waste clearance and cognitive decline.

Date: 2025
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DOI: 10.1038/s41467-025-61889-6

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