Abstract
Growing old is the greatest risk factor for the development of intervertebral disc degeneration (IDD), an underlying condition of many debilitating spine-related disorders including chronic back pain. Understanding the biology of intervertebral disc aging to develop effective interventions to minimize the adverse effects of aging on disc health is imperative, given the rapid global growth of the aging population. Recent research studies have begun to shed light on the basic biological process of disc aging. Accumulation of DNA damage was recently demonstrated as a key molecular driver of aging of the intervertebral discs. This talk summarizes the major findings that shed lights on the molecular mechanisms of how disc DNA damage is induced and the consequences of accumulated DNA damage on disc cell phenotype and extracellular matrix homeostasis. In particular, cellular senescence emerges as a central mediator of age-related disc degenerative changes which originated from DNA damage. The molecular processes of how DNA damage induces disc cellular senescence leading to perturbation of disc matrix homeostasis and matrix proteglycan loss through the NF-kB signaling are discussed in details. Key molecular steps involved in generation of DNA damage, formation of senescence, and activation of NF-kB signaling in disc cells will be highlighted as novel therapeutic targets along with the emerging candidate therapeutics that may mitigate age-associated IDD.
Disclosures: None