There are a multitude of products for sale that promise the appearance of eternal youth by erasing wrinkles or firming up jaw lines; but what if we could truly turn back time, at the cellular level? Now, researchers from Japan have found a protein that may do just that.
In a study published this month in Cellular Signaling, researchers from Osaka University have revealed that a key protein is responsible for toggling between 'young' and 'old' cell states.
As we age, older, fewer active cells, known as senescent cells, accumulate in multiple organs. These cells are noticeably larger than younger cells, and exhibit altered organization of stress fibers, the structural parts of cells that help them move and interact 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."
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.
Fig.
Increased AP2A1 Expression During Cellular Senescence
Credit： Chantachotikul et al., Osaka University
The article, "AP2A1 modulates cell states between senescence and rejuvenation," was published in Cellular Signaling at DOI:
