www.pnas.org\/doi\/10.1073\/pnas.2416433122?url_ver=Z39.88-2003&
\nrfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed<\/a><\/p>\nAbstract;
\nUnderstanding the key drivers of brain aging is essential for effective
\nprevention and treatment of neurodegenerative diseases. Here, we
\nintegrate human brain and physiological data to investigate underlying
\nmechanisms. Functional MRI analyses across four large datasets (totaling
\n19,300 participants) show that brain networks not only destabilize
\nthroughout the lifetime but do so along a nonlinear trajectory, with
\nconsistent temporal "landmarks" of brain aging starting in midlife (40s).
\nComparison of metabolic, vascular, and inflammatory biomarkers
\nimplicate dysregulated glucose homeostasis as the driver mechanism for
\nthese transitions. Correlation between the brain’s regionally
\nheterogeneous patterns of aging and gene expression further supports
\nthese findings, selectively implicating GLUT4 (insulin-dependent glucose
\ntransporter) and APOE (lipid transport protein). Notably, MCT2 (a
\nneuronal, but not glial, ketone transporter) emerges as a potential
\ncounteracting factor by facilitating neurons’ energy uptake
\nindependently of insulin. Consistent with these results, an
\ninterventional study of 101 participants shows that ketones exhibit
\nrobust effects in restabilizing brain networks, maximized from ages 40
\nto 60, suggesting a midlife "critical window" for early metabolic
\nintervention.<\/p>\n
\u3088\u308d\u3057\u304f\u304a\u9858\u3044\u81f4\u3057\u307e\u3059\u3002<\/p>\n
\u91ce\u53e3 \u6df3<\/p>\n","protected":false},"excerpt":{"rendered":"
\u4e0b\u8a18\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3055\u305b\u3066\u9802\u304f\u4e88\u5b9a\u3067\u3059\u3002 Brain aging shows nonlinear transitions, suggesting a midlife "critical window" f…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-547","post","type-post","status-publish","format-standard","hentry","category-journal-club"],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/547","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=547"}],"version-history":[{"count":1,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/547\/revisions"}],"predecessor-version":[{"id":553,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/547\/revisions\/553"}],"wp:attachment":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=547"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=547"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=547"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}