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Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression

Venia Batziou, Alexandra Young, Timothy Rittman, Vesna Vuksanovic Orcid Logo

medRxiv

Swansea University Authors: Venia Batziou, Vesna Vuksanovic Orcid Logo

DOI (Published version): 10.1101/2025.10.19.25337876

Abstract

Ageing is marked by widespread cortical changes, but the molecular underpinning and network connectivity shaping this variability remain poorly understood. We analysed structural MRI from 952 adults aged 18–94 using morphometric similarity networks, subtype/stage inference, and cortical transcriptom...

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Published in: medRxiv
Published: Cold Spring Harbor Laboratory
URI: https://cronfa.swan.ac.uk/Record/cronfa70902
first_indexed 2025-11-14T10:30:28Z
last_indexed 2026-01-13T05:32:00Z
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spelling 2026-01-12T22:01:31.9296234 v2 70902 2025-11-14 Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression 35a4b3e1c71f435e8dfdf2a35f442eaa Venia Batziou Venia Batziou true false a1a6e2bd0b6ee99f648abb6201dea474 0000-0003-4655-698X Vesna Vuksanovic Vesna Vuksanovic true false 2025-11-14 Ageing is marked by widespread cortical changes, but the molecular underpinning and network connectivity shaping this variability remain poorly understood. We analysed structural MRI from 952 adults aged 18–94 using morphometric similarity networks, subtype/stage inference, and cortical transcriptomics. Based on intra-network connectivity within three major cortical networks and their associations with longevity genes, two robust subtypes emerged. The normative-ageing subtype (metabolic-immune) showed connectivity profiles consistent with typical age-related decline and was enriched for genes involved in metabolism, insulin signalling, and immune regulation. The compensatory subtype (stress-repair) displayed more preserved intra-network connectivity and was linked to stress-response, DNA repair, and proteostasis genes. Although the two subtypes overlap in oxidative stress and neurodegeneration pathways, their distinct molecular signatures capture biologically meaningful differences in cortical ageing. By integrating network-based morphometry with transcriptomics, we establish a novel framework to distinguishes normative decline from compensatory adaptation in ageing profiles to provide biologically informed markers of brain ageing. Journal Article medRxiv Cold Spring Harbor Laboratory 0 0 0 0001-01-01 10.1101/2025.10.19.25337876 Preprint article before certification by peer review. COLLEGE NANME COLLEGE CODE Swansea University Not Required This work was supported by the BRACE Charity Research Grant (DSR1085-100). V.B. was supported by this grant. A.Y. was funded by the Wellcome Trust (grant number 227341/Z/23/Z). 2026-01-12T22:01:31.9296234 2025-11-14T10:21:32.3249858 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Health Data Science Venia Batziou 1 Alexandra Young 2 Timothy Rittman 3 Vesna Vuksanovic 0000-0003-4655-698X 4 70902__35632__5a79c6b278fa4ec4827331deac54b6e9.pdf medRxiv_MSN_SuStain_vv.pdf 2025-11-14T10:30:04.3778470 Output 40692253 application/pdf Pre-print true false 340
title Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
spellingShingle Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
Venia Batziou
Vesna Vuksanovic
title_short Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
title_full Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
title_fullStr Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
title_full_unstemmed Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
title_sort Network subtypes of cortical similarity reveal molecular correlates of normative and compensatory ageing associated with longevity genes expression
author_id_str_mv 35a4b3e1c71f435e8dfdf2a35f442eaa
a1a6e2bd0b6ee99f648abb6201dea474
author_id_fullname_str_mv 35a4b3e1c71f435e8dfdf2a35f442eaa_***_Venia Batziou
a1a6e2bd0b6ee99f648abb6201dea474_***_Vesna Vuksanovic
author Venia Batziou
Vesna Vuksanovic
author2 Venia Batziou
Alexandra Young
Timothy Rittman
Vesna Vuksanovic
format Journal article
container_title medRxiv
institution Swansea University
doi_str_mv 10.1101/2025.10.19.25337876
publisher Cold Spring Harbor Laboratory
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Health Data Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Health Data Science
document_store_str 1
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description Ageing is marked by widespread cortical changes, but the molecular underpinning and network connectivity shaping this variability remain poorly understood. We analysed structural MRI from 952 adults aged 18–94 using morphometric similarity networks, subtype/stage inference, and cortical transcriptomics. Based on intra-network connectivity within three major cortical networks and their associations with longevity genes, two robust subtypes emerged. The normative-ageing subtype (metabolic-immune) showed connectivity profiles consistent with typical age-related decline and was enriched for genes involved in metabolism, insulin signalling, and immune regulation. The compensatory subtype (stress-repair) displayed more preserved intra-network connectivity and was linked to stress-response, DNA repair, and proteostasis genes. Although the two subtypes overlap in oxidative stress and neurodegeneration pathways, their distinct molecular signatures capture biologically meaningful differences in cortical ageing. By integrating network-based morphometry with transcriptomics, we establish a novel framework to distinguishes normative decline from compensatory adaptation in ageing profiles to provide biologically informed markers of brain ageing.
published_date 0001-01-01T05:34:03Z
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score 11.096068

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