Key result
Apelin-13 preserves disc structure and reduces senescence-pyroptosis signaling via AMPK-driven autophagy during IDD.
Why the study?
Impaired autophagy is a hallmark of disc aging in intervertebral disc degeneration, but its upstream regulation remains unclear.
Apelin-13 protects against intervertebral disc degeneration by restoring autophagy and reducing senescence and pyroptosis via the AMPK-TFEB axis.
Hypothesis-generating for apelin-13 in IDD; extends rodent autophagy data but leaves human translation open.
Intervertebral disc degeneration (IDD) is an aging-associated disorder driven by chronic inflammation. Impaired autophagy is a hallmark of disc aging, but its upstream regulation remains unclear. Here, we identify Apelin-13 (APL13) as an endogenous peptide that restores autophagic competence in degenerative nucleus pulposus (NP) cells. APL13 alleviated IL-1β-induced senescence and pyroptosis. It also restored autophagic flux by promoting TFEB activation and nuclear translocation. Mechanistically, APL13 activated AMPK signaling pathways. It enhanced TFEB-dependent lysosomal and autophagy programs through both the AMPK-mTOR axis and the AMPK-FOXO3a-SKP2-CARM1 axis. In a lumbar spine instability mouse model, APL13 preserved disc structure, maintained ECM integrity, and reduced senescence-pyroptosis signaling in vivo. These findings position APL13 as a regulator of disc inflammaging. And the AMPK-TFEB axis emerges as a key pathway linking autophagy restoration to NP cell during IDD progression.
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Gong et al. (2025) studied this question. Apelin-13 preserved disc structure and reduced senescence-pyroptosis signaling in vivo, enhancing autophagy via AMPK and TFEB activation in nucleus pulposus cells during IDD.
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