Klotho Expression in Aging and Disease

Klotho is a regulatory anti-aging protein that is significantly expressed in the choroid plexus, plays an important role in regulating the immune response in the CNS, and diminishes with age. It is known that a decline of klotho expression has been linked to significant neuroinflammation, oxidative damage in the neural parenchyma, and decline in neurocognitive functions. As the choroid plexus is a known reservoir for latent Human Immunodeficiency Virus (HIV) infection, the relationship between HIV and klotho expression could be a cause of the neurocognitive dysfunction that accompanies HIV infections. The objective of this project was to observe levels of klotho expression in the choroid plexus in a Simian Immunodeficiency Virus (SIV) model of HIV infection, as well as to determine a pattern of age-related decline in klotho expression. To carry out the study, Choroid plexus samples of Rhesus macaques of various ages and SIV-infection status were studied. The tissues were stained using immunohistochemistry for polyclonal klotho, structural proteins (vimentin), and nuclei (DAPI), and imaged at varying magnifications of 4x, 10x, and 40x. The images obtained were then analyzed using the fluorescent imaging software Fiji. The epithelial cells of the choroid plexus were measured for their fluorescence intensity to measure their relative klotho expression levels. Although klotho expression was varied in the uninfected Rhesus macaques, there was an overall decreasing trend with the advancement of age. In SIV-infected Rhesus macaques, the choroid plexus had significantly less klotho expression than the uninfected control group regardless of age (p=0.01). Analysis of the uninfected data shows that there was a decreasing pattern of klotho expression in Rhesus macaques. The variability of klotho levels in the uninfected individuals can be attributed to genetic variations between individuals. However, SIV infection significantly reduced klotho expression in the choroid plexus in comparison to uninfected individuals. This decrease in klotho expression was regardless of age. The exact mechanism in which SIV diminishes klotho expression is unknown and additional studies are warranted to examine this phenomenon. Publisher Note: This is the full abstract presented at the Experimental Biology meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract.

Creator

• Choe, David
• MacLean, A. G.
• Delery, Elizabeth

Publisher

• Federation of American Societies for Experimental Biology (FASEB)

Language

• English

Identifier

• DOI: https://doi.org/10.1096/fasebj.2022.36.S1.L6382

Parola chiave

• immune response
• regulatory anti-aging protein
• Simian Immunodeficiency Virus (SIV) model of HIV infection
• latent Human Immunodeficiency Virus (HIV) infection

Date created

• 2022

Related URL

• available from the library catalog:  https://marianunivindianapolis.on.worldcat.org/oclc/9462337632
• Available from the publisher:  https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2022.36.S1.L6382

Resource type

• Article

Source

• The FASEB Journal (Vol. 36, Iss.S1)

Rights statement

• http://rightsstatements.org/vocab/InC/1.0/