Downregulation of senescence-associated secretory phenotype by knockdown of secreted frizzled-related protein 4 contributes to the prevention of skin aging

Kento Takaya, Toru Asou, Kazuo Kishi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8167-8178
Number of pages12
JournalAging
Volume14
Issue number20
DOIs
Publication statusPublished - 2022

Keywords

  • Fibroblast
  • Sasp
  • Sfrp4
  • Skin

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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