Many longevity mechanisms depend on the body's ability to activate stress signaling pathways and proteostatic mechanisms, but during the process of aging, many of the ways that our body responds to stress starts to decline. One of the consequences of not being able to activate stress signalling pathways and proteostasis is degeneration in neural tissue. In one study, the collapse of proteostasis due to aging is linked to protein aggregation and degenerative phenotypes in neural tissue (Taylor & Dillin, 2011). But what if administration of a common antibiotic could slow that progression?
Enter: minocycline. A group of scientists recently found that the antibiotic minocycline both increases the lifespan and reduces protein aggregation in older, stress-signaling pathway deficient C. elegans. The minocycline targets cytoplasmic ribosomes and attentuates the translation of the mRNAs that lead to the proteins that are prone to aggregation. Slowing down the translation of these proteins is what the stress-signaling pathway normally does to activate the body's integrated stress response. Essentially, the minocycline is able to bypass the activation of the stress signaling pathway (that is less efficient with age) to attenuate translation of these proteins, leading to less aggregation (Solis et al., 2018).
Since protein aggregates in the brain (precipitating as insoluble amyloid fibrils) are what cause the deterioration in patients with Alzheimer's, it seems like this is a great step toward developing an effective treatment (Irvine et al., 2008). My only concern with this is given the rise of antibiotic resistance and the prevalence of neurodegenerative disesases like Alzheimer's disease with ~44 million people globally (source) and Parkinson's disease with ~10 million people globally (source), if antibiotic treatment becomes a common practice in these patients, what will be the impact on antibiotic resistance?
Sources:
Irvine, G. B., El-Agnaf, O. M., Shankar, G. M., & Walsh, D. M. (2008). Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases. Molecular Medicine, 14(7-8), 451-464. doi: 10.2119/2007-00100.Irvine.
Solis, G. M., Kardakaris, R., Valentine, E. R., Bar-Peled, L., Chen, A. L., Blewett, M. M., McCormick, M. A., Williamson, J. R., Kennedy, B., Cravatt, B. F., & Petrascheck, M. (2018). Translation attenuation by minocycline enhances longeviety and proteostasis in old post-stress-responsive organisms. Elife, 7. doi: 10.7554/eLife.40314
Taylor, R.C. & Dillin, A. (2011). Aging as an event of proteostasis collapse. Cold Springs Harbor Perspectives in Biology. doi: 10.1101/cshperspect.a004440
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