Zombie outbreaks aren’t limited to popular TV shows, movies, and video games. In aging skin, these “undead” cells—known as senescent cells—linger indefinitely, damaging neighboring skin and making it susceptible to wounds that won’t heal. Now, Johns Hopkins engineers have developed a treatment that targets these cells, offering hope for the millions struggling with slow-healing wounds and other age-related skin conditions.
Led by Efie Kokkoli, a professor of chemical and biomolecular engineering at the Whiting School of Engineering, the team’s approach—supported in part by NIH’s National Institute on Aging—combines two common existing medications in a gel that targets senescent cells, often called zombie cells, while stimulating skin’s collagen production. The team’s results, “Co-Delivery of Valsartan and Metformin from a Thermosensitive Hydrogel-Nanoparticle System Promotes Collagen Production in Proliferating and Senescent Primary Human Dermal Fibroblasts,” appear in Biomacromolecules.
“We present a novel strategy using valsartan—a common blood pressure medication—and metformin—used for diabetes—in a temperature-responsive gel-based delivery system to rejuvenate aging skin cells and enhance collagen production. Our targeted, extended-release delivery system offers patient-friendly therapies that combat cellular aging and restore skin integrity, bridging research with clinical applications,” said Kokkoli, a core researcher at Johns Hopkins Institute for NanoBioTechnology and targeted drug-delivery expert.
As a person ages, they lose collagen, the protein that keeps skin healthy and flexible. Collagen loss, combined with dysfunction of older cells, can slow down the body’s natural healing mechanisms, making skin prone to tearing, even from minor trauma, and increasing the risk of ulcers, sores, and wounds that don’t heal easily. While traditional treatments like wound dressings and antibiotics can help prevent infection, they fail to repair the underlying conditions.
The team’s treatment strategy, which involves compounds that directly address senescent cells, represents a breakthrough in anti-aging research because it zeroes in on aging cells directly, reversing senescence and promoting cell growth while stimulating collagen production in both senescent and healthy cells.
In laboratory tests, the team found that metformin rejuvenated senescent cells, helping them regain function, multiply, and reduce telltale signs of aging. Meanwhile, valsartan boosted collagen production in cells derived from both young and old adults.
“Although still in early experimental stages, this work lays the foundation for developing topical treatments that could improve wound healing and address age-related skin conditions in older adults,” Kokkoli said.
Study co-authors include Paul M. Kuhn, a former graduate student in chemical and biomolecular engineering and INBT affiliate now at TD Cowen, Siwei Chen, and Aditya Venkatraman, both graduate students in chemical and biomolecular engineering and INBT affiliates, as well as Peter Abadir, an associate professor, and Jeremy Walston, a professor—both of the School of Medicine.
This study was supported by the Johns Hopkins University Older Americans Independence Center of the National Institute on Aging and the Whiting School of Engineering of the Johns Hopkins University.