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Does Cellular Senescence Drive Aging in Intervertebral Discs? New R01 Grant is Exploring Molecular Mechanisms at Play in IDD

January 9, 2024

Nam VoNam V. Vo, PhD, co-director of the Ferguson Laboratory for Orthopaedic and Spine Research was awarded a 2023 National Institutes of Health R01 grant that will further his ongoing research into the cellular and molecular mechanisms that lead to intervertebral disc degeneration (IDD).

The grant, titled “Mechanisms of Cellular Senescence Driving Intervertebral Disc Aging Through Local Cell Autonomous and Systemic Non-Cell Autonomous Processes,” is designed to more fully characterize how the process of cellular senescence associated with aging leads to degradation of intervertebral disc tissues and ultimately pathological spine conditions and low back pain. The project builds on prior findings that link persistent DNA damage in aging cells to the onset of cellular senescence and their subsequent acquisition of the senescence-associated secretory phenotype (SASP). SASP is characterized by the release of inflammatory and catabolic factors by senescent cells, which are implicated in the degradation of disc matrix, which is a core aspect of IDD.

What is Cellular Senescence?

Cellular senescence (CS) occurs when cells cease to divide and undergo distinctive biological changes. CS is a hallmark of the aging process, acting as a protective mechanism, primarily against the development of cancer. When cells sense damage or stress, such as DNA damage, they take on a senescent state to prevent the changed or mutated cell from replicating and propagating its damaged genomic DNA. Senescent cells remain metabolically active but no longer replicate themselves, but their SASP can have deleterious effects on surrounding tissues, for example intervertebral discs.


Clearance of cellular senescence by GCV improves intervertebral disc proteoglycan matrix. Red: aggrecan. Blue: Nuclei

Grant Details – Aims and Potential Clinical Applications

Dr. Vo’s study is investigating the dual role of cellular senescence - whether it predominantly acts through local, cell-autonomous processes within the disc tissue, or through systemic, non-cell autonomous mechanisms via senescent cells in other tissues-in driving age-related IDD. This distinction is crucial for understanding the pathophysiology of disc aging and devising targeted interventions. For example, if IDD is influenced systemically, then treating IDD locally without account for other body tissues would not be effective. Additionally, the study also explores the contributions of two distinct cellular senescence mechanisms, p16INK4a and p21Cip1-mediated pathways, in IDD.


Treatment of aging mice with the nucleotide analog GCV eliminates senescent cells (red circles) without harming normal cells (green).

Dr. Vo’s research has significant potential implications for clinical practice. By characterizing the exact role of cellular senescence in driving age-related IDD and understanding which pathways - p16INK4a vs. p21Cip1 - contribute locally and globally to the formation of IDD, it may potentially lead to the identification of novel senolytic therapies that are more effective and targeted approaches to treating IDD.

Grant Reference

Mechanism of Cellular Senescence Driving Intervertebral Disc Aging Through Local Cell Autonomous and Systemic Non-Cell Autonomous Processes. Project Number: 1R01AG081293. Principal Investigator: Nam V. Vo, PhD. Funding: National Institute on Aging – Skeletal Biology Structure and Regeneration Study Section.

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