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Co-Director of the Ferguson Laboratory for Orthopaedic and Spine Research, Nam Vo, PhD, was recently awarded a Research Project Grant (R01) from the National Institutes of Health (NIH) to study intervertebral disc degeneration. The grant is being funded by the National Institute on Aging.
The study, titled, “Mechanisms of Cellular Senescence Driving Intervertebral Disc Aging through Local Cell Autonomous and Systemic Non-Cell Autonomous Processes,” aims to determine if cellular senescence mainly drive disc aging locally, systemically, or both.
Intervertebral disc degeneration (IDD) underlies many spinal disorders resulting in debilitating back pain, disability, and tremendous economic loss. Aging is the greatest risk factor for IDD and yet the biology of disc aging is still poorly understood. Based on his lab preliminary data suggesting how a class of cell type known as cellular senescence drives age-IDD, Dr. Vo hypothesizes that local effects of p21-mediated disc cellular senescence are only partially responsible for driving age dependent IDD, and that contribution from p16-mediated systemic cellular senescence is necessary to fully account for the observed aging-dependent IDD phenotype.
There are three proposed specific aims to test this hypothesis using several innovative transgenic mouse strains: (1) Determine the relative contributions of local (cell autonomous) and systemic (non-cell autonomous) processes in driving disc cellular senescence and age- dependent IDD; (2) Determine the relative contributions of p21CIP1 and p16INK4a -mediated cellular senescence on age-dependent IDD; and (3) Test whether treatment with senolytics, drugs that selectively eliminate senescent cells, can slow age-dependent IDD.
The proposed studies aim to elucidate the molecular and cellular mechanisms through which cellular senescence promotes disc aging and identify therapeutic drug interventions to mitigate age-dependent intervertebral disc degeneration at the systemic and local disc tissue level.
According to the National Institutes of Health (NIH), the R01 is the original and historically oldest grant mechanism used by NIH. The R01 provides support for health-related research and development based on the mission of the NIH. It is a $526,910 grant and spans five years.
See more research by Nam Vo, PhD.