Highlights

  • ABT-263 is a senolytic compound that eliminates aging (senescent) cells, significantly lowering senescence markers p16 and p21 in the skin of aged mice. 
  • Pre-treated mice exhibited faster wound healing, with 80% achieving full wound closure by day 24 compared to 56% in the untreated group.

Aging skin is more than just a cosmetic concern. It reflects deeper biological changes that weaken its ability to heal. As we grow older, skin regeneration slows, wounds take longer to close, and the risk of complications like infections and scarring increases. Traditional anti-aging treatments aim to hydrate and stimulate collagen production, but they fail to address one of the key drivers of skin deterioration: cellular senescence.

Now, researchers may have found a solution. A new study highlights the potential of ABT-263, a senolytic compound designed to eliminate aged, dysfunctional cells. By targeting senescent cells, which drive inflammation and hinder tissue repair, ABT-263 has shown promising results in rejuvenating aged skin and accelerating wound healing. These findings, published in Aging, could revolutionize skincare and post-surgical recovery, offering new hope for millions of aging individuals.

The Role of Cellular Senescence in Skin Aging

Cellular senescence is a state of permanent cell cycle arrest that occurs when cells encounter various stressors, such as DNA damage, oxidative stress, or telomere shortening. While this mechanism serves as a protective barrier against the proliferation of damaged cells, the accumulation of senescent cells over time can disrupt tissue homeostasis and contribute to the aging process.

What makes senescent cells particularly harmful is that they secrete destructive molecules called the senescence-associated secretory phenotype (SASP). Not only can the SASP trigger inflammation, a known hallmark of aging, but it can also promote the degradation of the extracellular matrix and collagen. As a result, this SASP activity disrupts the structural integrity and regenerative capacity of the skin, leading to common signs of aging, including wrinkles, loss of elasticity, and impaired wound healing.

To counteract these effects, researchers have turned to senolytics, a class of compounds designed to selectively eliminate senescent cells. Among the most studied senolytic compounds is ABT-263, also known as navitoclax, a small-molecule inhibitor that targets anti-apoptotic proteins Bcl-2 and Bcl-xL. By disrupting these survival pathways, ABT-263 triggers apoptosis (cell death) specifically in senescent cells, thereby reducing their presence in tissues and restoring regenerative potential. 

Given its senolytic effects, researchers sought to determine whether ABT-263 could rejuvenate aging skin and enhance wound healing.

ABT-263 Enhances Skin Repair and Healing 

Since senescent cells disrupt skin regeneration, the study investigated whether ABT-263 could enhance skin health by eliminating these aging cells. Gene analysis revealed that aged (24-month-old) mice treated with topical ABT-263 exhibited significantly lower levels of two key senescence markers, p16 and p21—both of which contribute to chronic inflammation and hinder tissue repair. Further analysis confirmed that ABT-263 treatment also reduced senescence-associated beta-galactosidase (SA-β-gal), a well-established marker of cellular aging. Together, these findings strongly indicate that ABT-263 effectively counters cellular senescence in aged skin.

With evidence of successful senescent cell clearance, researchers next examined whether ABT-263 could improve wound healing in mice with an excisional wound on the dorsal skin. The results were striking. Mice pretreated with ABT-263 demonstrated a dramatically enhanced healing capacity. By day 18 post-injury, nearly 33% of treated mice had achieved complete wound closure, compared to none in the untreated group. By day 24, 80% of the ABT-263 group had fully healed, a 24% improvement over untreated mice. 

Genetic analysis further revealed that ABT-263 activated key pathways involved in tissue regeneration, including extracellular matrix remodeling and angiogenesis. Collectively, these findings suggest that eliminating senescent cells not only prevents further skin deterioration but also primes the skin for enhanced repair and renewal.

(Shvedova et al., 2025 | Aging) ABT-263 decreases skin senescence and improves wound healing. (Left) Mice treated with ABT-263 (red) exhibit less p21 cell activity than untreated mice (blue). (Right) By day 24, complete wound healing was observed in 80% of mice that received ABT-263 (red) before injury, compared to only 56% in the untreated group (blue).  

Implications for Surgical Recovery and Geriatric Care

The ability of ABT-263 to enhance wound healing has profound implications, particularly for elderly patients undergoing surgery. Each year, approximately 4 million major surgical procedures are performed on individuals aged 65 and older in the United States. Older patients face a higher risk of complications due to delayed wound healing and increased susceptibility to infections. The findings suggest that preoperative treatment with ABT-263 could help improve skin recovery following surgery, potentially reducing complications and improving surgical outcomes.

By targeting senescent cells, ABT-263 offers a new strategy for addressing one of the key challenges in geriatric medicine: impaired tissue regeneration. While the results in mice are promising, further studies are necessary to determine whether these effects translate to human subjects. If proven effective, senolytic-based preoperative treatments could become an essential tool in improving post-surgical healing and reducing hospital stays for elderly patients.