Credit: https://www.lifespan.io/news/senescence-associated-protein-promotes-skin-aging-in-mice/
Suppressing SFRP4 Protein Reverses Skin Aging in Mice
September 8, 2022
- Scientists have established that suppressing the protein SFRP4 reverses skin aging in mice.
- By treating groups of mice with an effective RNA treatment for SFRP4, they observed a reduced expression of SASP components linked to cellular senescence.
- Researchers are now hopeful that suppressing SFRP4 could provide an effective treatment against skin aging in human trials.
Scientists have recently published a paper in the journal Aging identifying an individual protein—SFRP4 (secreted frizzled=related protein 4)—that is produced by senescent cells and promotes skin aging in mice.
Previous studies had established that SFRP4 is more pronounced with aging and that the molecule stimulates cells to become senescent. As you age, the high levels of SFRP4 pose a hazard to tissue health, stimulating bone loss in aging, promoting tissue fibrosis, and aggravating health issues in patients with colon cancer.
Researchers kicked off the study by analyzing cellular senescence and comparing non-proliferating human skin fibroblasts to proliferating ones. As they expected, the normal markers of the SASP were documented; including interleukins, TNF-α, and MMP3. Moreover, senescent fibroblasts had 3000 times the SFRP4 compared to their proliferating counterparts.
The researchers also wanted to determine whether SFRP4 made other cells senescent. They did this by administering SFRP4 to a culture of proliferating human fibroblasts. They observed that the proliferating cells behaved more like senescent cells, releasing some of the common SASP components at nearly the same rate as senescent cells.
To confirm these findings, the researchers then used RNA silencing to prevent senescent fibroblasts from expressing SFRP4. As expected, these fibroblasts expressed lesser SASP components linked to senescence.
This, therefore, confirmed the relationship between SFRP4 and SASP in fibroblasts. The researchers then experimented with mice models.
In this experiment, the mice were divided into four groups: young 15-week-old mice, a control group of 90-week-old mice, another control group of 90-week-old mice given ineffective RNA treatment, and lastly, a group of 90-week-old mice given an effective RNA treatment against SFRP4 for four weeks.
Similar to the human cell tests, there was a reduced expression of the SASP in all the mice receiving treatment compared to the control groups. In fact, the skins of the treated groups shared strong similarities to the skin of young mice under a microscope—exhibiting youthful collagen structures.
Scientists are now hopeful that the possibility of human trials could develop a therapy that targets excess SFRP4 production at the source and reduces the spread of SASP, suppressing cellular senescence and providing an effective treatment against skin aging.
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