Nuclear condensates in aging-related diseases: The roles and diagnostic potential

Ruofei Li

1,#

Su Wu

2,#

Guang Shi

3,*

Hui Huang

1,*

Feng Liu

3,*

Affiliation +

*Correspondence to: Guang Shi, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China. E-mail: shguang@mail.sysu.edu.cn
Hui Huang, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518033, Guangdong, China. E-mail: huangh8@mail.sysu.edu.cn
Feng Liu, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, China. E-mail: liufeng23@mail.sysu.edu.cn

Geromedicine. 2027;3:202646. 10.70401/Geromedicine.2026.0046

Received: July 27, 2026Accepted: October 28, 2026Published: October 29, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Aging is a major risk factor for chronic diseases, and reliable biomarkers are urgently needed to improve healthspan. Nuclear condensates (NCs), membraneless organelles formed via liquid-liquid phase separation (LLPS), regulate essential nuclear functions including transcription, DNA repair, and RNA processing. This review summarizes recent advances in NC biology, focusing on their dynamic changes during cellular senescence and their dysregulation in major aging-related diseases, including neurodegeneration, cancer, progeroid syndromes, and cardiovascular diseases. Canonical NCs such as nucleoli, Cajal bodies, PML-NBs, nuclear speckles, paraspeckles, and heterochromatin domains undergo structural and functional remodeling with aging, and their dysregulation, manifested as morphological alterations, aberrant phase transitions, or mislocalization of components, contributes to disease pathogenesis. We also discuss the emerging, though still largely exploratory, potential of NCs as diagnostic biomarkers, highlighting both imaging and molecular strategies for clinical translation as well as the substantial challenges that remain. Finally, we outline key unanswered questions and future directions, with an emphasis on the need for standardized methodologies, causal mechanistic studies, and validated clinical assays. Collectively, this review suggests that NCs may offer new conceptual and therapeutic angles on aging-related diseases.

Keywords

Nuclear condensates, aging-related diseases, diagnostic potential

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Li R, Wu S, Shi G, Huang H, Liu F. Nuclear condensates in aging-related diseases: The roles and diagnostic potential. Geromedicine. 2027;3:202646. https://doi.org/10.70401/Geromedicine.2026.0046

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Geromedicine

Nuclear condensates in aging-related diseases: The roles and diagnostic potential

Ruofei Li

Su Wu

Guang Shi

Hui Huang

Feng Liu

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Nuclear condensates in aging-related diseases: The roles and diagnostic potential

Ruofei Li

Su Wu

Guang Shi

Hui Huang

Feng Liu

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