下記の論文を紹介させて頂く予定です。

Brain aging shows nonlinear transitions, suggesting a midlife "critical
window" for metabolic intervention.
Antal BB, van Nieuwenhuizen H, Chesebro AG, Strey HH, Jones DT, Clarke K,
Weistuch C, Ratai EM, Dill KA, Mujica-Parodi LR.
Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2416433122. doi: 10.1073/
pnas.2416433122. Epub 2025 Mar 3.
PMID: 40030017

下記のURL(先頭に`h`を追加下さい。)よりダウンロードが可能です。
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　ttps://www.pnas.org/doi/10.1073/pnas.2416433122?url_ver=Z39.88-2003&
rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed

Abstract;
Understanding the key drivers of brain aging is essential for effective
prevention and treatment of neurodegenerative diseases. Here, we
integrate human brain and physiological data to investigate underlying
mechanisms. Functional MRI analyses across four large datasets (totaling
19,300 participants) show that brain networks not only destabilize
throughout the lifetime but do so along a nonlinear trajectory, with
consistent temporal "landmarks" of brain aging starting in midlife (40s).
Comparison of metabolic, vascular, and inflammatory biomarkers
implicate dysregulated glucose homeostasis as the driver mechanism for
these transitions. Correlation between the brain’s regionally
heterogeneous patterns of aging and gene expression further supports
these findings, selectively implicating GLUT4 (insulin-dependent glucose
transporter) and APOE (lipid transport protein). Notably, MCT2 (a
neuronal, but not glial, ketone transporter) emerges as a potential
counteracting factor by facilitating neurons’ energy uptake
independently of insulin. Consistent with these results, an
interventional study of 101 participants shows that ketones exhibit
robust effects in restabilizing brain networks, maximized from ages 40
to 60, suggesting a midlife "critical window" for early metabolic
intervention.

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