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Heat Shock Protein Fights Senescence in Macular Degeneration

This finding explains many of its positive downstream effects.

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Researchers publishing in Experimental Eye Research have discovered that the peptide aB-crystallin can reduce the cellular senescence that affects the progression of age-related macular degeneration (AMD).

What is αB-crystallin?

αB-crystallin is a well-known heat shock protein, a family of proteins that is used in temperature regulation. This protein has been previously demonstrated by this research team to have positive effects on retinal pigment epithelium (RPE) cells, including its benefits for mitochondria [1], its positive effects on oxidative stress [2], and its ability to prevent cellular death [3].

With this study, the researchers pinpointed another effect of this protein, one that is related to those three and many more: cellular senescence. In order to manage its levels, they used a chaperone peptide, a collection of amino acids that is generally smaller than a protein, called mini Cry.

Cellular senescence seems to be negated by mini Cry

For this study, the researchers induced senescence in RPE cells by giving them a precise dose of the antibiotic doxorubicin. As expected, the cells were shown to have a senescent phenotype, as measured by SA-β-gal, p16, and p21 accumulation, which are common biomarkers of cellular senescence. Co-administration of mini Cry decreased these levels nearly to those of a control group that was never administered doxorubicin at all.

These results were confirmed by using mini Cry on cells that were driven senescent by oxidative stress, which was induced in this study through hydrogen peroxide. The effects of mini Cry on peroxide-treated cells were nearly identical to its effects on doxorubicin-treated cells.

The researchers also returned to the mitochondria that they studied previously, noting that mitochondrial biogenesis, the process by which mitochondria are created, is actually increased in cellular senescence. However, this is reduced back to, or below, untreated control group levels with the administration of mini Cry.

The mitochondria’s ability to perform their basic function, provide energy from glucose and oxygen through glycolysis, is also affected; glycolysis increases with cellular senescence as well, and mini Cry reduced it, also to levels below that of the control group in some cases.

Finally, the researchers chose to examine one of the most well-known and dreaded aspects of cellular senescence: the SASP. The inflammatory mediators and interleukins that are associated with the SASP, including TNF-α, IL-6, and IL-8, were decreased to or below control group levels with mini Cry.

The researchers examined a mouse model to briefly examine the effects of senescence on RPE cells, where they found evidence for its association with AMD and subretinal fibrosis, but they did not test the effects of mini Cry on it.

Conclusion

These researchers’ continued efforts and examinations of the biology of RPE cells has yielded interesting findings that might possibly be useful for the treatment of AMD. If mini Cry can be dosed and tested in animals and human beings, it may provide an amelioration of this common and often blinding disease.

However, possibly the most interesting finding from a life extension viewpoint is that the researchers have been measuring many different positive effects of αB-crystallin of over the years, all of which seem to hinge upon a single upstream cause. There is no such thing as a complete panacea, but if more research can be directed into treatments that can possibly provide broad and positive effects against multiple aspects of aging, such treatments could potentially ameliorate multiple “different” conditions at once.

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Literature

[1] Sreekumar, P. G., Wang, M., Spee, C., Sadda, S. R., & Kannan, R. (2020). Transporter-Mediated Mitochondrial GSH Depletion Leading to Mitochondrial Dysfunction and Rescue with aB Crystallin Peptide in RPE Cells. Antioxidants, 9(5), 411.

[2] Sreekumar, P. G., Li, Z., Wang, W., Spee, C., Hinton, D. R., Kannan, R., & MacKay, J. A. (2018). Intra-vitreal aB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration. Journal of Controlled Release, 283, 94-104.

[3] Sreekumar, P. G., Chothe, P., Sharma, K. K., Baid, R., Kompella, U., Spee, C., … & Hinton, D. R. (2013). Antiapoptotic properties of a-crystallin–derived peptide chaperones and characterization of their uptake transporters in human RPE cells. Investigative ophthalmology & visual science, 54(4), 2787-2798.

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About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
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