image: Figure 7. Runx1 overexpression induced NP cell senescence. (A, C) Immunohistochemistry staining for P21 (A) and P16 (B) was conducted to detect the presence of cell senescence in the NP. Scale bar = 200μm. (B, D) Quantification analysis showed that substantial increase in the ratio of P21 positive cells in Runx1 overexpression mice. P16 positive cells were increased significantly at 5M and 10M but not at 7M. n = 5 mice /group. Student’s t-test was performed (** p < 0.01). (E) The gene expression analysis demonstrated the increased levels of p21, p16, and Nf-kb in Runx1 overexpression mice at 10M. The expression level of p53 remained unchanged in the Runx1 overexpression mice. n = 5 mice /group. Student’s t-test was performed (** p < 0.01, * p < 0.05).
Credit: Copyright: © 2025 Fukunaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Taken together, these findings reveal a novel role of Runx1 in maintaining disc health and regulating age-related degenerative processes.”
BUFFALO, NY — October 17, 2025 — A new research paper was published in Volume 17, Issue 9 of Aging-US on September 8, 2025, titled, “Runx1 overexpression induces early onset of intervertebral disc degeneration.”
In this study, led by first author Takanori Fukunaga from Emory University School of Medicine and corresponding author Hicham Drissi from Emory and the Atlanta VA Medical Center, researchers found that the Runx1 gene, when overactive in spinal disc cells, can accelerate age-related degeneration of the intervertebral discs. The findings offer new insight into the genetic factors that drive disc aging and suggest possible directions for treating chronic back pain.
Intervertebral discs cushion the spine and support movement. Their deterioration is a major cause of lower back pain, especially with aging. At the center of each disc is the nucleus pulposus (NP), a gel-like core that contains proteins such as collagen and aggrecan, which help retain water and maintain structure. As people age, NP cells often lose their function, contributing to disc breakdown.
Using a genetically modified mouse model, the researchers activated Runx1 specifically in NP cells. These mice developed signs of disc degeneration by five months of age, which is much earlier than normal. The overexpression of Runx1 led to the loss of healthy NP cells, an increase in abnormal cell types, and damage to disc structure. Levels of essential proteins like aggrecan and type II collagen decreased, while type X collagen increased, signaling unhealthy tissue changes.
“To achieve NP-specific postnatal overexpression of Runx1, we crossed Krt19CreERT mice with Rosa26-Runx1 transgenic mice previously generated in our laboratory.”
A key finding was that Runx1 overactivity did not kill cells directly. Instead, it caused premature cellular aging, known as senescence. Senescent cells lose the ability to repair tissue, creating an environment that accelerates degeneration. Markers of senescence were significantly elevated in the affected discs.
The researchers also observed a dose-dependent response. The more Runx1 was activated, the more severe the degeneration was. This suggests that targeting Runx1 may be a promising strategy to prevent or slow disc aging.
Overall, this study highlights the genetic and cellular processes that contribute to intervertebral disc degeneration, a leading cause of disability. By identifying Runx1 as a potential driver of early disc aging, the research opens new opportunities for intervention and treatment of degenerative spine conditions.
DOI: https://doi.org/10.18632/aging.206316
Corresponding author: Hicham Drissi — hicham.drissi@emory.edu
Keywords: cell senescence, aging, Runx1, nucleus pulposus, intervertebral disc degeneration
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Runx1 overexpression induces early onset of intervertebral disc degeneration
Article Publication Date
8-Sep-2025
COI Statement
The authors declare that they have no conflicts of interest.