Tier 3 — preclinical

Fisetin-Mediated Topical Modulation of Senescent Cells in Skin Improves Wound Healing Dynamics in Diabetic Mice

Asfia Numani, Margarita Carrasco-Jeldres, Barbara Hernandez-Rovira, K-Raman Purushothaman, Matthew M. Melin, James L. Kirkland, Saranya Wyles
Advances in Wound Care 2026

Bibliography

PubMed
PMID 41730842
PubMed Central
PMC13078590
DOI
10.1177/21621918261426580
Funding
Supported by NIH T32 GM145408 and NIA R03 AG082919, with additional support from the Mayo Clinic Robert and Arlene Kogod Center on Aging and Mayo Clinic Department of Dermatology. Additional support for James L. Kirkland is disclosed in the paper.
Competing interests
James L. Kirkland disclosed financial interests including patents and pending patents covering senolytic drugs and their uses held by Mayo Clinic. The research was conducted under Mayo Clinic and Cedars-Sinai conflict-of-interest policies; the other authors reported no disclosures.

Study snapshot

DesignRandomized controlled topical-treatment study in diabetic mice.
Modeldb/db diabetic mice with full-thickness excisional dorsal wounds.
Sample24 mice total: topical vehicle n=12 and topical fisetin n=12; six per group were assessed at day 7 and six per group at day 21.
InterventionTopical fisetin or vehicle for three consecutive days per week after wound creation.
DurationOutcomes assessed through days 7 and 21 after wounding.
EndpointsWound closure; Healthy dermis-to-granulation ratio; Granulation tissue; Dermal fibrosis; p16-positive and p21-positive cells; TNF-α and IL-1β; M1 macrophages

What the study showed, in plain terms

In diabetic mice, topical fisetin altered several wound-healing and senescence-related measures. It increased the ratio of healthy dermis to granulation tissue at day 7, reduced fibrosis at day 21, lowered p16-positive cells and reduced selected inflammatory markers.

Importantly, the study did not show a significant acceleration of wound closure, and p21-positive cells increased at day 7. The work therefore supports a nuanced preclinical skin effect, not a claim that topical fisetin heals human wounds or rejuvenates human skin.

Key findings

  • Topical fisetin increased the healthy-dermis-to-granulation ratio at day 7 and reduced dermal fibrosis at day 21.
  • The treatment decreased p16-positive cells but increased p21-positive cells early in healing, showing that the senescence-marker response was not uniformly reduced.
  • TNF-α, IL-1β and later M1 macrophage measures were reduced.
  • Wound closure itself was not significantly accelerated.

What this study can and cannot tell us

  • Mouse diabetic-wound model: no human skin or wound-healing trial was performed.
  • Topical exposure cannot be used to infer the effects of oral fisetin supplements on skin.
  • Different senescence markers moved in different directions, so the biological effect is better described as senescence modulation than uniform senescent-cell clearance.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology