We evaluated the effects of NIC on frailty, physical function, and metabolic function using Caenorhabditis elegans (C. elegans) and aging mouse models. NIC effectiveness was assessed using behavioral experiments, histological analysis, and molecular biological analysis.
Results
We identified NIC as a compound that enhanced exercise capacity and metabolism, thereby alleviating frailty. Briefly, NIC extended the lifespan and improved frailty-related phenotypes in C. elegans, and effectively ameliorated frailty in aging mice, particularly in muscle aging. Additionally, NIC treatment suppressed the muscle atrophy-related ubiquitinâproteasome system induced by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation, while enhancing autophagic flux, another aspect of proteostasis. Furthermore, mRNA-seq analysis revealed that NIC improved metabolism-related functions.
Conclusion
Collectively, these findings suggest that NIC is a promising novel candidate for the prevention of frailty.
I was wondering if I could reply to you due my chronic ignorance:)
They found that niclosamide (anthelmintic medication) was capable to enhance the process of autophagy in muscles (while suppressing mTORC1) in vivo.
Past studies had shown that autophagy is diminished in frailty. Reduced autophagy causes impaired cellular function.
Autophagy, metabolism (mTOR, AMPK) and cellular function work hand in hand. Interconnected processes that maintain cellular function and homeostase.
I like your explanation better than theirâs. It just doesnât make sense to me that blocking fuel intake and blocking the primary energy metabolism could improve exercise capacity.
I think that the anti-aging effect of niclosamide is no less than that of rapamycin, and niclosamide seems to have better safety. The only drawback is that its oral bioavailability is a bit low. Iâm in China, and niclosamide is only available in the form of veterinary medicine for treating tapeworms. So, Iâve currently started taking veterinary niclosamide. Referring to the methods in research papers, my current way of taking niclosamide is to take 500 milligrams in the morning, 250 milligrams at noon, and 500 milligrams in the evening, chewing it thoroughly and taking it with meals, which can increase its bioavailability to a certain extent.
The term âmagic bulletâ is a scientific concept proposed by the German Nobel laureate Paul Ehrlich in 1907, describing a medicine that could specifically and efficiently target a disease without harming the body. Oncologists have been looking for a magic bullet for cancer therapy ever since. However, the current therapies for cancersâincluding chemotherapy, radiation therapy, hormone therapy, and targeted therapyâpose either pan-cytotoxicity or only single-target efficacy, precluding their ability to function as a magic bullet. Intriguingly, niclosamide, an FDA-approved drug for treating tapeworm infections with an excellent safety profile, displays broad anti-cancer activity in a variety of contexts. In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-ÎşB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK. Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1. We recently discovered that niclosamide ethanolamine (NEN) reprograms cellular metabolism through its uncoupler function, consequently remodeling the cellular epigenetic landscape to promote differentiation. Inspired by the promising results from the pre-clinical studies, several clinical trials are ongoing to assess the therapeutic effect of niclosamide in cancer patients. This current review summarizes the functions, mechanism of action, and potential applications of niclosamide in cancer therapy as a magic bullet.