{"id":12228,"date":"2025-07-22T09:55:44","date_gmt":"2025-07-22T07:55:44","guid":{"rendered":"https:\/\/www.uni.lu\/lcsb-en\/?post_type=news&p=12228"},"modified":"2025-07-30T17:20:20","modified_gmt":"2025-07-30T15:20:20","slug":"rejuvenating-the-brain-with-the-help-of-a-computational-clock","status":"publish","type":"news","link":"https:\/\/www.uni.lu\/lcsb-en\/news\/rejuvenating-the-brain-with-the-help-of-a-computational-clock\/","title":{"rendered":"Rejuvenating the brain with the help of a computational clock"},"content":{"rendered":"\n
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What if there was a way to make ageing brain cells younger again? Researchers from Luxembourg and Spain recently set out to address this question. After developing an ageing clock capable of assessing the biological age of the brain, they used it to identify possible brain-rejuvenating interventions. The computational tool they created, recently presented in the journal Advanced Science<\/em><\/a>, constitutes a valuable resource to find compounds with therapeutic potential for neurodegenerative diseases.<\/p>\n\n\n\n

As the world population is ageing rapidly, with over two billion people projected to be above the age of 60 by 2050, age-related brain disorders are on the rise. Living longer but in poor health is not only a daunting prospect, it also places a substantial burden on healthcare systems worldwide. The idea of being able to counteract the functional decline of our brain through rejuvenating interventions sounds therefore promising. The question is how can we identify compounds that have the potential to efficiently rejuvenate brain cells and to protect the ageing population from neurodegeneration? Prof. Antonio Del Sol<\/a> and his teams of computational biologists, based both at the LCSB<\/a> from the University of Luxembourg and at the CIC bioGUNE<\/a> in Bilbao, used their machine learning expertise to tackle the challenge.<\/p>\n\n\n\n

\nBuilding a clock to measure the biological age of the brain<\/h2>\n\n\n\n

The researchers developed what is called an \u201cageing clock\u201d, a computational tool designed to measure the biological age of cells, as opposed to their chronological age. Indeed, the organs and tissues of people of the same age can evolve differently over time depending on genetic and environmental factors, leading to different biological ages. These clocks are therefore useful tools to assess ageing at the molecular level and can help in understanding its causes and consequences.<\/p>\n\n\n\n

The clock designed by the LCSB and CIC bioGune researchers is specific to the brain and uses gene expression information from 365 genes to make predictions. Using a machine learning approach, it was trained on data from healthy individuals, aged from 20 to 97, and could accurately predict their age. Further tests showed that the clock is able to estimate the biological age of different cell types in the brain, especially neurons. Lastly, by looking at the predicted biological ages for healthy individuals and for patients with neurological conditions, the researchers observed that patients exhibited a higher biological age.<\/p>\n\n\n\n

\u201cOur results tell us that the biological age of the brain cells calculated by our clock reflects the decline in brain function experienced by the patients, especially between 60 and 70, and is even correlated with the degree of neurodegeneration,\u201d explains Dr Guillem Santamaria<\/a>, first author of the study. \u201cIt supports the view of neurodegeneration as a form of accelerated ageing but, more importantly, the positive association between neurodegeneration and biological age suggests that the rejuvenating interventions identified by the clock could serve as neuroprotective agents.\u201d<\/p>\n\n\n\n

\nIdentifying compounds that have a rejuvenating potential<\/h2>\n\n\n\n

The aim of the researchers was to use the clock to find genetic or chemical interventions that would signi\ufb01cantly shift back the biological age of brain cells. They explored the effect of thousands of compounds on neural progenitor cells and neurons and identified 453 unique rejuvenating interventions.<\/p>\n\n\n\n

Among the identified compounds that have the potential to reverse the biological age of the two types of brain cells, several are known to extend lifespan in animal models and some are already used to treat neurological disorders, but the vast majority has not yet been studied in the context of health- or lifespan extension. \u201cOn the one hand, the fact that our computational platform identified drugs that have a known effect on brain function supports the idea that using the predicted effect of a compound on the biological age is an efficient way to evaluate its neuroprotective potential,\u201d details Prof. Antonio Del Sol, head of the Computational Biology<\/a> groups at the LCSB and CIC BioGUNE. \u201cOn the other, the results also highlight that our clock can help us find many new candidates that haven\u2019t been studied before for their rejuvenating properties. It opens up a lot of new avenues.\u201d<\/p>\n\n\n\n

\nFirst validation in animal model and broadening the therapeutic horizon<\/h2>\n\n\n\n

As a proof of concept of their approach, the researchers then tested three of the predicted compounds in mice, in collaboration with the team of Prof. Rub\u00e9n Nogueiras at the Centre for Research in Molecular Medicine and Chronic Diseases<\/a>. The administration of these drugs signi\ufb01cantly reduced anxiety and slightly increased spatial memory in older mice, addressing two well-known symptoms associated with ageing. An analysis of gene expression showed that the combination of these compounds also led to a shift toward a younger phenotype. Altogether, these results show that a selection of compounds predicted to rejuvenate the brain did produce rejuvenation at the molecular level in the cortex of aged mice and had an impact on behavioural and cognitive functions.

Globally, the study, recently published in the journal Advanced Science<\/em><\/a>, highlights the computational ageing clock developed by the researchers as a valuable resource for identifying brain-rejuvenating interventions with therapeutic potential in neurodegenerative diseases. It provides a strong foundation for further research. \u201cThe hundreds of compounds predicted by our platform require validation across multiple biological systems to assess their e\ufb03cacy and safety, o\ufb00ering extensive opportunities for future therapeutic development,\u201d concludes Prof. Antonio Del Sol.<\/p>\n\n\n\n

———
Watch the short interview of Dr Sascha Jung explaining the study.<\/strong><\/a>


Reference: <\/strong>Guillem Santamaria, Cristina Iglesias, Sascha Jung, Javier Arcos Hodar, Ruben Nogueiras and Antonio del Sol, A machine-learning approach identi\ufb01es rejuvenating interventions in the human brain<\/a>, Advanced Science<\/em>, July 2025.

This research is supported by the Fondation Jean Think.

Credits: Top image is AI generated<\/sub><\/p>\n\n\n

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\nMeet the LCSB researchers<\/h2>\n
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    \n \n\"Prof\n <\/figure>\n <\/div>\n
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    Prof Antonio DEL SOL MESA<\/h3>\n

    Full professor \/ Chief scientist 1 in Bioinformatics<\/p>\n

    \n \n \n Learn more<\/span>\n <\/span>\n <\/use><\/svg> <\/a>\n<\/div>\n <\/div>\n <\/div>\n<\/div>\n<\/div><\/li>
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    \n \n\"Dr.\n <\/figure>\n <\/div>\n
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    Dr. Guillem SANTAMARIA AGUILAR<\/h3>\n

    Postdoctoral researcher<\/p>\n

    \n \n \n Learn more<\/span>\n <\/span>\n <\/use><\/svg> <\/a>\n<\/div>\n <\/div>\n <\/div>\n<\/div>\n<\/div><\/li><\/ul>\n\n<\/div>\n\n<\/div><\/section>\n\n\n
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    \nDiscover more<\/h2>\n\n
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    • \n \n \n \n The LCSB Computational Biology group <\/span>\n <\/use><\/svg> <\/span>\n <\/a>\n<\/li>\n\n\n\n
    • \n \n \n \n Computational Biology Lab at CIC bioGUNE <\/span>\n <\/use><\/svg> <\/span>\n <\/a>\n<\/li>\n\n\n\n
    • \n \n \n \n SINGULAR, the cell rejuvenation atlas <\/span>\n <\/use><\/svg> <\/span>\n <\/a>\n<\/li>\n<\/ul>\n <\/div>\n<\/section>","protected":false},"excerpt":{"rendered":"","protected":false},"author":55,"featured_media":12238,"template":"","format":"standard","meta":{"featured_image_focal_point":{"x":0,"y":0.5},"show_featured_caption":false,"ulux_newsletter_groups":"","uluxPostTitle":"","uluxPrePostTitle":"","_trash_the_other_posts":false,"_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_tribe_ticket_capacity":"0","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false},"news-category":[4],"news-topic":[10,19],"organisation":[205,202],"authorship":[55],"acf":[],"yoast_head":"\nRejuvenating the brain with the help of a computational clock - University of Luxembourg<\/title>\n\n\n\n\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n\n\t\n