Countering skin aging possible through cellular protein regulation, study finds

02 Nov 2022 --- Japan-based research findings may aid in the development of anti-aging skin treatments by preventing age-related changes in aging cells via the regulation of secreted frizzled-related protein 4 (SFRP4) expression.

The study conducted by researchers from Keio University School of Medicine’s Department of Plastic and Reconstructive Surgery found that SFRP4 in the dermal fibroblasts of aging skin and its increased expression has been linked to cellular deterioration.

“These results may contribute to developing new therapies to ameliorate skin aging,” the researchers say.

The researchers add that there is growing evidence that the appearance and texture of the skin that are altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts.

Role of SASP and SFRP4
The senescent cells magnify aging via an inflammatory, histolytic and senescence-associated secretory phenotype (SASP). Previously found to be expressed in dermal fibroblasts of aging skin, SFRP4 has been shown to promote cellular senescence. However, its role in the SASP is still unclear.

“This study shows that SFRP4, specifically expressed in aged p16ink4a-positive – a marker for cellular deterioration – skin fibroblasts, contributes to SASP. Furthermore, treatment with SFRP4 causes worsening of this phenotype,” the researchers add.

Researchers note that the study findings may contribute to the development of skin anti-aging treatments.“To the best of our knowledge, the present study is the first to report that the suppression of SFRP4 expression in-vivo ameliorates skin aging-related phenotypes, that is, adipose tissue atrophy and collagen fiber thinning, via SASP suppression.”

In p16ink4a-positive human skin fibroblasts, SFRP4 was found to be significantly expressed. Treatment with recombinant SFRP4 increased SASP and senescence, while SFRP4 siRNA knockdown decreased SASP.

Additionally, the researchers discovered that SFRP4 knockdown in mice skin reduces the aging-related loss of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and the thinned and dispersed collagen fibers.

These results point to a potential candidate for the creation of novel SASP-suppressive skin rejuvenation treatments.

Limitations and future research
One limitation of this study is that the other effects of SFRP4 knockdown on the skin were not thoroughly investigated – some of the SASP perform important biological functions in wound healing and response to short-term tissue damage.

Interventions targeting senescent cells in the context of aging and aging-related diseases may need to be temporally and locally specific to particular conditions to avoid interfering with the beneficial functions of the aging phenomenon.

This can be done by using SFRP4 knockdown mice to conduct additional research on the precise mechanisms of senescent cell function suppression.

Future studies on female mice are required to consider applications in humans, as this study only used male mice to avoid any effects attributable to changing hormone levels.

In recent skin aging moves, Givaudan Active Beauty introduced Siliphos – a botanical skincare ingredient pegged as the “first” natural cosmetic alternative that provides anti-aging advantages equal to retinoids. Meanwhile, a Slovenia-based study found that retinoid-based nanocosmetics show promising anti-aging properties for the skin.

Edited by Nicole Kerr

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