There is increasing evidence that the appearance and texture of skin, which changes during the aging process, is greatly improved by the accumulation of senescent dermal fibroblasts. These senescent cells enhance senescence via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP).

Secreted protein 4 (SFRP4) was previously found to be expressed in the dermal fibroblasts skin aging, and its increased expression has been shown to promote cellular aging. However, his role in the SASP remains unknown.

In a new study published in Agingresearchers Kenta Takaya, Toru Asu, and Kazuo Kishi from Keio University’s Department of Plastic and Reconstructive Surgery investigated the classical model of skin fibroblasts based on Hayflick’s mitotic limit, observing the expression of SFRP4 in replicating senescent cells and the effect of its regulation on the suppression of SASP and skin aging.

“These results may contribute to the development of new treatments to alleviate skin aging,” say the researchers.

The researchers found that SFRP4 is significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promotes SASP and senescence, while siRNA knockdown of SFRP4 suppresses SASP. They also found that knockdown of SFRP4 in the skin of mice alleviated the age-related decline in subcutaneous adipose tissue, the panniculus muscle layer, and the thinning and scattering of collagen fibers. These findings indicate a potential candidate for the development of novel skin rejuvenation techniques that suppress SASP.

“This study shows that SFRP4, which is specifically expressed in senescent p16ink4a-positive skin fibroblasts, contributes to SASP, and that SFRP4 treatment exacerbates this phenotype. To our knowledge, this study is the first to report that suppression of SFRP4 expression in vivo ameliorates phenotypes associated with skin aging, i.e., adipose tissue atrophy and collagen fiber thinning, through suppression of SASP,” the researchers said.

“Overall, this study could potentially aid in the development of treatments for skin aging by preventing age-related changes through the regulation of SFRP4 expression in senescent cells.”

Courtesy of Impact Journals