Crowdsourced Drug Discovery Approach Identifies BET Inhibitors As Novel Geroprotectors Promoting Healthy Aging - Abstract

Sep 29, 2026

The elderly population is expanding, creating a socio-economic challenge that requires reliable biomarkers to extend healthspan and lifespan. The study targets age-associated misexpression of CGI-genes, which drives chronic inflammation and loss of cell identity. Calorie restriction, fasting, and methionine restriction suggest pharmacological suppression could promote healthy aging. A crowdsourced, in silico machine-learning drug discovery approach identifies BET inhibitors as geroprotectors. Experimental validation shows 14-week BET inhibition suppresses muscle, balance, memory decline, delays epigenetic aging, and improves survival in aged mice.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages1

Reading Time3 min

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Crowdsourced In Silico Drug Discovery Approach

Targeting CGI-Gene Misexpression

Identification of BET Inhibitors

Experimental Validation and Outcomes

1166 Innovation in Aging, 2025, Vol. 9, No. S2 socio-economic challenge. Identification and targeting of reliable biomarkers are essential for developing effective strategies to extend healthspan and lifespan. One promising target is age-associated misexpression of genes lacking CpG islands (CGIgenes), which is commonly observed across a broad range of aged tissues and contributes to chronic inflammation and loss of cell identity. Notably, established anti-aging interventions, such as calorie restriction, fasting, and a methionine-restriction diet, inhibits this dysregulation, suggesting that pharmacological suppression of CGI-gene misexpression would provide an effective strategy to promote healthy aging. To streamline this process, we developed a novel in silico drug discovery approach leveraging crowdsourced transcriptomic data and machine learning. Our approach significantly outperformed existing resources such as Connectivity Map, which exhibit crucial weaknesses in capturing pathological gene expression patterns in vivo. We analyzed CGIgene expression in drug-treated vs. control groups using over 100,000 GEO samples and identified BET-inhibitors as potential geroprotectors suppressing CGI- gene misexpressions. Our experimental validation demonstrates that long-term (14-week) treatment with BET inhibitor effectively suppresses age-associated decline in muscle strength, body balance, and memory function, delays epigenetic aging, and promotes better survival in aged mice. Taken together, our study demonstrates that a pharmacological targeting of CGI-gene misexpression using a BET inhibitor provides an effective strategy for promoting healthy aging. In addition, our novel crowdsourced drug discovery approach offers an effective and practical solution for combating aging and associated diseases. Abstract citation ID: igaf122.3908 CROWDSOURCED DRUG DISCOVERY APPROACH IDENTIFIES BET INHIBITORS AS NOVEL GEROPROTECTORS PROMOTING HEALTHY AGING Byungju Kim, and Samuel Beck, Boston University, Boston, Massachusetts, United States The significant growth of the elderly population, driven by advances in biomedical science and public health, poses a critical

FAQs

What is the biological target of this study?

The study focuses on age-associated misexpression of CGI-genes (genes lacking CpG islands), which is linked to chronic inflammation and loss of cell identity.

How were candidate drugs identified?

A novel in silico approach uses crowdsourced transcriptomic data and machine learning, outperforming existing resources in capturing pathological gene expression patterns.

What results were observed after long-term BET inhibitor treatment?

A 14-week BET inhibitor treatment suppresses age-related declines in muscle strength, body balance, and memory function, delays epigenetic aging, and improves survival in aged mice.

Sep 29, 2026

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