SFRP4 Knockdown Suppresses the Senescence-Associated Secretory Phenotype in Senescent Skin Cells

Researchers here note that SFRP4 is expressed in aged skin cells, and especially in senescent skin cells. Gene knockdown of SFRP4 in mice was shown to reduce the harmful signaling generated by these cells, the senescence-associated secretory phenotype (SASP), and improve measures of skin aging in the treated animals. On the whole, modulating the SASP seems a poor strategy in comparison to selectively destroying senescent cells with senolytic therapies. For one, a SASP-suppressing treatment is unlikely to suppress all of the diverse molecular components of the SASP, and secondly has to be taken continuously over time. A senolytic treatment definitely gets rid of the SASP, whether or not researchers can currently measure it, and needs to be taken only intermittently.

There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence. However, its role in the SASP remains unknown.

We found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promoted SASP and senescence, whereas siRNA knockdown of SFRP4 suppressed SASP. Furthermore, we found that knockdown of SFRP4 in mouse skin ameliorates age-related reduction of subcutaneous adipose tissue, panniculus carnosus muscle layer, and thinning and dispersion of collagen fibers. These findings suggest a potential candidate for the development of new skin rejuvenation therapies that suppress SASP.

Link: https://doi.org/10.18632/aging.204273