Therapeutic Effects of Autophagy Activation for Acne

woman with acne applying cream to her face.
Conceptual of acne problems on woman skin.
The effects of an autophagy activator on acne-prone skin were investigated and reported.

Topical treatment with an autophagy activator may improve skin barrier function in patients with acne or acne-prone skin, study data published in the Journal of Cosmetic Dermatology suggests. In cultured human sebocytes and keratinocytes, an autophagy-activating test peptide was found to increase autophagy signaling and inhibit lipogenesis. In a companion clinical study, topical application of the same peptide was associated with fewer comedones and reduced trans-epidermal water loss (TEWL).

Investigators conducted both in vitro and clinical studies to assess the impact of an autophagy-activating peptide on acne-prone skin. The in vitro models used human immortalized SZ95 sebocytes, normal human epidermal keratinocytes (NHEKs), and a reconstituted 3-dimensional human skin model. The test peptide was pentasodium tetracarboxymethyl heptadecanoyl dipeptide-12—. To stimulate lipogenesis, sebocytes were treated with testosterone and linoleic acid for 48 hours. NHEKs and SZ95 sebocytes were treated with either a control peptide (trehalose) or the autophagy activating peptide for 24 hours. Effects of autophagy activation on these cells were assessed using enhanced chemiluminescence. The 3-dimensional skin model was similarly treated with vehicle or test peptide, then fixed and embedded in paraffin for immunohistochemical analysis. For the clinical portion of the study, patients with acne were instructed to apply a topical product containing either placebo or the autophagy activating test peptide twice daily for 8 weeks. Lesion count and trans-epidermal water loss (TEWL) were evaluated at baseline and at weeks 2, 4, 6 and 8. In addition, skin surface lipids were collected by D-Squame tape for evaluation at baseline and follow-up. Wilcoxon signed rank tests were performed to evaluate clinical differences from baseline to follow-up.

The test peptide increased microtubule-associated protein 1 light chain 3 (LC3)-II protein expression in cultured sebocytes and NHKEs, suggesting elevated autophagy signaling. In SZ95 sebocytes with induced lipogenesis, the test peptide demonstrated sebaceous lipid-suppressive effects. Test peptide-treated sebocytes also displayed increased expression of differentiation marker proteins. In the reconstituted skin model, increased expression of LC3 protein was observed in the suprabasal layer, confirming the autophagy activating effects of the test peptide.

The clinical study cohort comprised 49 patients with acne, of whom 32 were women. Mean age was 24.8 ± 4.1 years. In the treatment group, the number of whiteheads was reduced from 29.1 at baseline to 20.1 at week 8. In the group that used placebo, no significant reductions in whiteheads were observed. Skin surface lipids were also substantially reduced in the test group during 8 weeks. Specifically, a significant reduction in squalene was observed in the test group at 8 weeks (P <.05). The same effect was not observed in the control group. An increase in cholesterol was also observed in test peptide-treated skin at 8 weeks (P <.05). Reduced TEWL was observed in both patient groups at 4 and 8 weeks (all P <.05).

The data suggest topical application of an autophagy activator may be a therapeutic option for patients with acne, the study authors believe. Further research in a large clinical cohort are necessary to confirm these findings. “[C]ombination of autophagy-activating peptides with other ingredients can improve the clinical outcomes of topical formulation or alleviate the adverse effects of topical formulation by lowering the concentration of potentially irritating active ingredients,” investigators wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.


Lee Y, Shin K, Shin KO, et al. Topical application of autophagy-activating peptide improved skin barrier function and reduced acne symptoms in acne-prone skin [published online July 22, 2020]. J Cosmet Dermatol. doi: 10.1111/jocd.13636