Table 3 Cellular senescence and other age-related mechanisms in IVDD
From: Cellular senescence and other age-related mechanisms in skeletal diseases
Cell types | Molecules or signals | Variation | Effect | References |
|---|---|---|---|---|
NPCs | SASP | Up | Accelerates inflammation and degradation of the disc matrix | |
CTGF/CCN2 | Down | Increases matrix metalloproteinases and ECM breakdown | ||
Piezo1 | Up | Promotes mitochondrial dysfunction and inflammatory infiltration | ||
CircERCC2 | Down | Regulates NPCs’ aging through the miR-182-5p/SIRT1 cascade | ||
Keap1/Nrf2/Wnt5a | Down | Protects NPCs from senescence | ||
cGAS/STING | Up | Promotes inflammation and cellular senescence | ||
ROS | Up | Promotes mitochondrial dysfunction | ||
p53/p21 | Up | Promotes disc degeneration | ||
GLRX3 | Down | Disrupts redox homeostasis and contributes to cellular senescence | ||
NLRX1 | Down | Promotes mitochondrial rupture and excessive mitochondrial autophagy | ||
TNF | Up | Triggers calcium overload-induced cellular senescence | ||
SHH | Down | Promotes AFCs losing their polarity and characteristic hierarchical structure | ||
AFCs | Keap1/Nrf2/Wnt5a | Down | Promotes senescence and extracellular matrix breakdown | |
ROS | Up | Promotes cellular senescence | ||
CD133/Notch1/Jagged1/C-KIT/CD166 | Down | Reduces stem cell pluripotency markers | ||
CEPCs | Proteoglycan | Down | Accelerates ECM calcification | |
Type X collagen | Up | Accelerates ECM calcification | ||
Nutrients/Oxygen | Down | Accumulates harmful metabolites | ||
OCs | Netrin-1 | Up | Mediates the gradual growth of sensory nerves into aged endplate tissue | |
PGE2 | Up | Activates PKA/CREB and induces low back pain in elderly individuals | ||
Hippo | Up | Initiates cartilage endplate remodeling through activation of the OCs differentiation gene CCL3 | ||
MACs | IL-10 | Up | Leads to endplate sclerosis by affecting STAT3 signaling pathways |
