Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study.
Zhu. Daxue D; Wang. Zhaoheng Z; Li. Yanhu Y; Chen. Shijie S; Kang. Xuewen X
Key Findings
- Humanin levels are reduced in intervertebral disc degeneration (IDD) patients and models
- Exogenous humanin raises endogenous humanin, blocks JAK2/STAT3 and NF‑κB pathways, and reduces ferroptosis in nucleus pulposus cells
- Humanin preserves mitochondrial function, lowers mtROS and mtDNA leakage, and improves disc structure in a rat IDD model
Practical Outcomes
- While the findings are promising, humanin is not yet ready for self‑administration or clinical use. Biohackers should view this as a signal that humanin may become a future anti‑degeneration supplement, but more human safety and dosing studies are needed before any protocol can be recommended.
Summary
Researchers found that the tiny protein humanin, which the body makes in mitochondria, is lower in people with back‑disc damage. Adding extra humanin in cell cultures and rats boosted the body’s own humanin, protected disc cells from a type of cell death called ferroptosis, and improved disc health in rats. The work shows humanin could one day be a treatment for disc degeneration, but it’s still early‑stage animal research.
Abstract
Intervertebral disc degeneration (IDD) is a prevalent etiology of low back pain in the global adult population, leading to considerable morbidity and healthcare costs. Existing therapeutic modalities for IDD remain constrained. Ferroptosis in the nucleus pulposus (NP) cells emerges as a pivotal contributor to IDD. Humanin (HN), a mitochondrial-secreted peptide, is intricately linked to age-related maladies and showcases antioxidant, anti-inflammatory, and anti-apoptotic properties. Nonetheless, its precise involvement in IDD remains enigmatic. The expression profile of HN in IDD was scrutinized utilizing human NP cell cultures and an IDD rat model (n = 5). The therapeutic efficacy of HN in rats was assessed via MRI and histological evaluation, alongside an exploration of the molecular underpinnings of HN's therapeutic actions in IDD management. This pioneering study unveiled a downregulation of HN expression in IDD patients, a finding corroborated through cell and rat IDD models. Furthermore, it was ascertained that exogenous HN could trigger endogenous HN expression, impede the JAK2/STAT3 and NF-κB pathways, thereby mitigating erastin-induced ferroptosis in NP cells, contingent upon the upregulation of HSP27 expression. Moreover, the study validated the role of HN in preserving mitochondrial homeostasis, curbing mitochondrial reactive oxygen species (mtROS) generation and mtDNA leakage, consequently hindering mtDNA binding to TLR9 and subsequent activation of the NF-κB pathway. Notably, in vivo rat experiments underscored the efficacy of HN treatment in ameliorating IDD progression induced by annulus fibrosus puncture. By assuaging ferroptosis in NP cells, HN exhibits promise as a viable candidate for IDD treatment, capable of impeding disease advancement. <b>The translational potential of this article</b>: This study highlights the importance and effectiveness of HN in alleviating IDD by inhibiting ferroptosis in NP cells. The addition of exogenous HN may represent a potential therapeutic strategy for treating IDD.
Study Information
pubmed
2025
2025-01-21T00:00:00.000Z
10.1016/j.jot.2024.12.002
4
75