Researchers from Osaka University have discovered that the protein subunit AP2A1 may play a role in the unique structural organization of senescent cells.

There are countless products on the market that claim to restore a youthful appearance by reducing wrinkles or tightening the jawline. But what if aging could be reversed at the cellular level? Researchers in Japan may have uncovered a way to do just that.

A recent study published in Cellular Signaling by scientists at Osaka University identifies a key protein that regulates the transition between “young” and “old” cell states.

As the body ages, senescent cells—older, less active cells—accumulate in various organs. These cells are significantly larger than younger ones and display structural changes, including altered organization of stress fibers, which are essential for movement and interaction with their environment.

“We still don’t understand how these senescent cells can maintain their huge size,” says lead author of the study Pirawan Chantachotikul. “One intriguing clue is that stress fibers are much thicker in senescent cells than in young cells, suggesting that proteins within these fibers help support their size.”

The Role of AP2A1 in Cellular Senescence

To explore this possibility, the researchers examined AP2A1 (Adaptor Protein Complex 2, Alpha 1 Subunit). AP2A1 is a protein that is upregulated in the stress fibers of senescent cells, including fibroblasts, which create and maintain the skin’s structural and mechanical characteristics, and epithelial cells. The researchers eliminated AP2A1 expression in older cells and overexpressed AP2A1 in young cells to determine the effect on senescence-like behaviors.

“The results were very intriguing,” explains Shinji Deguchi, senior author. “Suppressing AP2A1 in older cells reversed senescence and promoted cellular rejuvenation, while AP2A1 overexpression in young cells advanced senescence.”

Furthermore, the researchers found that AP2A1 is often closely associated with integrin β1, a protein that helps cells latch onto the scaffolding-like collagen matrix that surrounds them, and that both AP2A1 and integrin β1 move along stress fibers within cells. In addition, integrin β1 strengthened cell–substrate adhesions in fibroblasts; this might explain the cause of the raised or thickened structures characteristic of senescent cells.

“Our findings suggest that senescent cells maintain their large size through improved adhesion to the extracellular matrix via AP2A1 and integrin β1 movement along enlarged stress fibers,” concludes Chantachotikul.

Given that AP2A1 expression is so closely linked to signs of aging in senescent cells, it could potentially be used as a marker for cellular aging. The research team’s work may also provide a new treatment target for diseases that are associated with old age.

Reference: “AP2A1 modulates cell states between senescence and rejuvenation” by Pirawan Chantachotikul, Shiyou Liu, Kana Furukawa and Shinji Deguchi, 21 January 2025, Cellular Signalling.
DOI: 10.1016/j.cellsig.2025.111616