Caloric Restriction Attenuated Nerve Damages Mediated Through SIRT-1-a Study Using Nerve Crush Injury Model in Rats

Activation of Sirtuin 1 (SIRT-1) is vital for axonogenesis and nerve regeneration. Caloric restriction (CR) has health benefits and protects against neurodegenerative disorders, largely through SIRT-1 regulation. This study investigates how diet control impacts peripheral nerve injury, focusing on SIRT-1 expression. We prepared nerve tissue cultures for a pharmacological analysis of SIRT-1's effects on nerve degeneration. After two weeks of 70% caloric restriction, we crushed the left sciatic nerve of Sprague-Dawley rats with a vessel clamp. We then administered SIRT-1 agonists or antagonists intraperitoneally. Nerve explant cultures showed increased SIRT-1 expression with SRT-1720, which was reduced by EX527, indicating enhanced regeneration. In the animal study, diet control led to notable SIRT-1 expression in plasma. This expression increased with SIRT-1 agonists and decreased with antagonists. SIRT-1 levels in paw skin were strongly correlated with PGP 9.5 and collagen deposition, while nerve fiber size and regeneration markers (S-100 and NF) also correlated with SIRT-1 expression. Inflammatory markers showed an inverse relationship with SIRT-1. TNF-α and NGF in the dorsal root ganglion responded reciprocally to SIRT-1 expression. Increased acetylcholine receptors and desmin in denervated muscle were parallel to SIRT-1 levels, with similar trends observed in muscle weight and diameter. Neurobehavioral and electrophysiological results aligned with these measurements. Caloric restriction has a preventative effect on nerve damage, mainly through SIRT-1 modulation. From a health perspective, promoting caloric restriction is important for mitigating nerve injury severity.