Inhibits SFRP4 to downregulate the aging-related secretory phenotype, helping to prevent skin aging

"Overall, this research may contribute to the development of anti-aging therapies that prevent age-related changes
by modulating the expression of SFRP4 in senescent cells.
"

A new research paper, published on the cover of Aging (listed as "Aging (Albany NY)" by Medline/PubMed and "Aging-us" by Web of Science), on the cover of Vol.
14, Issue 20, titled "Downregulating aging-related secretory phenotypes by inhibiting curl-related protein 4 helps prevent skin aging
.
" ”

There is increasing evidence that changes in skin appearance and texture during aging are significantly enhanced by the accumulation of senescent dermal fibroblasts
.
These senescent cells amplify aging
through inflammation, tissue lysis, and senescence-related secretory phenotypes (SASPs).

Secretion of curl-associated protein 4 (SFRP4) has previously been shown to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence
.
However, its role in SASP remains unknown
.

In the new study, Kento Takaya, Toru Asou, and Kazuo Kishi of the Department of Plastic and Reconstructive Surgery, Keio University, School of Medicine, studied a classical model of skin fibroblasts based on the mitosis limit of Hayflick, observed the expression of SFRP4 in replicating senescent cells, and the effects
of modulating this expression on inhibition of SASP and skin aging.

"These results may help develop new therapies
to improve skin aging.
"

The researchers found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts, with recombinant SFRP4 treatment promoting SASP and aging, and siRNA knockout SFRP4 inhibiting SASP
.
They also found that downregulation of the SFRP4 gene in mouse skin improved age-related reductions
in thinning and dispersion of subcutaneous adipose tissue, abdominal muscle layer, and collagen fibers.
These findings provide a potential candidate for the development of new skin rejuvenation therapies that inhibit SASP
.

"This study shows that SFRP4 is specifically expressed in senescent p16ink4a-positive skin fibroblasts and contributes to SASP, and treatment with SFRP4 can lead to a deterioration
of this phenotype.
" To our knowledge, the current study is the first to report an improvement in skin aging-related phenotypes, namely adipose tissue atrophy and collagen fiber thinning
, by inhibiting SFRP4 expression in vivo by inhibiting SASP.
”

DOI: https://doi.
org/10.
18632/aging.
204273