Article: Nicotinamide Riboside Maintains Mitochondrial Health in Intervertebral Disc Degeneration: Preclinical Findings

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Bone Health Healthy Aging & Longevity Mitochondrial Health Preclinical

Nicotinamide Riboside Maintains Mitochondrial Health in Intervertebral Disc Degeneration: Preclinical Findings

Synopsis

This study explored how the mitochondrial unfolded protein response (UPRmt) protects cells in the intervertebral disc from damage by activating mitophagy, the process that clears defective mitochondria. Researchers identified Sesn2 as a key link between UPRmt and mitophagy. When Sesn2 was silenced, it blocked the protective effects of nicotinamide riboside (NR)—a compound that boosts NAD+ and supports mitochondrial health—on nucleus pulposus (NP) cells, which are crucial for disc integrity. UPRmt increased Sesn2 expression through the Eif2ak4/eIF2α/Atf4 signaling pathway, leading to mitophagy activation by helping Parkin and Sqstm1 move to damaged mitochondria. In mice lacking Sesn2, disc degeneration was more severe, and NR treatment could not fully reverse it. These findings show that NR helps prevent intervertebral disc degeneration (IVDD) by promoting Sesn2-dependent mitophagy, offering new insights into mitochondrial repair mechanisms for spine health and aging-related disc disease.

Journal

International Journal of Biological Sciences

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