Publications

Latest publication 02/18/2026

Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculatu

Summary Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived...

Array
(
    [id_prestablog_news] => 2438
    [id_shop] => 1
    [date] => 2026-02-18 00:00:00
    [date_modification] => 2026-02-18 00:00:00
    [langues] => ["1","2"]
    [actif] => 1
    [slide] => 0
    [url_redirect] => 
    [average_rating] => 
    [number_rating] => 
    [author_id] => 1
    [featured] => 0
    [ishero] => 0
    [prim_key] => 4629
    [id_lang] => 1
    [title] => Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculatu
    [paragraph] => Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature
    [content] => 
Authors
Gregor Bieri, Karishma J.B. Pratt, Yasuhiro Fuseya, Turan Aghayev, Juliana Sucharov, Alana M. Horowitz, Amber R. Philp, Karla Fonseca-Valencia, Rebecca Chu, Mason Phan, Laura Remesal, Shih-Hsiu J. Wang, Andrew C. Yang, Kaitlin B. Casaletto, Saul A. Villeda

 Lab

Journal
Cell
Abstract
Summary
Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive rejuvenation for translational application. We identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on the brain vasculature as a GPLD1 substrate. Mimicking age-related increases in cerebrovascular TNAP impaired blood-brain transport and cognition in young mice and mitigated GPLD1-induced cognitive benefits in aged mice. Inhibiting TNAP recapitulated the benefits of GPLD1 in old age, restoring youthful hippocampal transcriptional signatures and rescuing cognition. In an Alzheimer's disease model, increasing GPLD1 or inhibiting TNAP ameliorated Aβ pathology and improved cognitive deficits. We thus identify brain vasculature as a mediator of the cognitive benefits of a liver-to-brain exercise axis.

Keywords/Topics
aging; rejuvenation; Alzheimer’s disease; exercise; GPLD1; liver; vasculature; blood-brain barrier; blood factors; cognition
BIOSEB Instruments Used:
Grip strength test (BIO-GS4)
    [meta_description] => 
    [meta_keywords] => https://www.cell.com/cell/fulltext/S0092-8674(26)00111-X?
    [meta_title] => 
    [link_rewrite] => Liver-exerkine-reverses-aging--and-Alzheimer’s-related-memory-loss-via-vasculature
    [actif_langue] => 1
    [read] => 0
    [count_comments] => 0
    [id] => 2438
    [categories] => Array
        (
            [63] => Array
                (
                    [id_prestablog_categorie] => 63
                    [title] => General muscular system
                    [link_rewrite] => General-muscular-system
                )

            [2] => Array
                (
                    [id_prestablog_categorie] => 2
                    [title] => Publications
                    [link_rewrite] => publications
                )

        )

    [authors] => 
    [paragraph_crop] => Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature
    [link_for_unique] => 1
    [products_liaison] => Array
        (
            [48] => Array
                (
                    [name] => Grip strength test
                    [description_short] => 
An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/bioseb2024/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://bioseb.com/en/activity-motor-control-coordination/48-grip-strength-test.html
                )

        )

)
1