Scientists find protein AP2A1 that may reverse aging effects. Scientists find protein that may reverse cellular aging by manipulating this protein, they were able to rejuvenate aged cells a finding that may lead to new anti-aging therapies.
As we age, according to their research, our cells become senescent, meaning they no longer divide and become bigger with thicker stress fibers. This transformation impacts the way cells behave and respond to their environment.
“We still don’t know how these senescent cells can sustain their enormous size,” said study lead author Pirawan Chantachotikul. “A tantalizing clue is that stress fibers are considerably thicker in senescent cells compared to young cells, indicating that proteins in these fibers contribute to their support of size.”
This led researchers to investigate which proteins might be responsible for this change and that’s when they discovered AP2A1. They found that AP2A1 is abundant in aging cells. To test its effects, they manipulated the protein’s levels and observed the results.
Shinji Deguchi, the lead author, said that the study was quite incredible.
Knocking down AP2A1 in older cells reversed senescence and induced cellular rejuvenation, on the other hand overexpression of AP2A1 in young cells accelerated senescence.
Briefly, lowering AP2A1 caused aging cells to act like young cells, whereas elevating it accelerated young-cell aging. Additional studies showed that AP2A1 binds to another significant protein, integrin β1, to keep cells in proper shape. This finding indicates that targeting AP2A1 might restore cell function, increase collagen synthesis, and possibly prevent diseases of aging.
Although this study is in its infancy, it’s an encouraging move toward learning about and potentially regulating the aging process. The research, published in Cellular Signalling, points to the thrilling possibility of attacking cellular processes such as AP2A1 to combat aging from the inside out.
Previously, it was reported that with the patronage of Zaki Nusseibeh, Cultural Adviser to the UAE President and Chancellor of UAEU, the United Arab Emirates University (UAEU) launched the nation’s first academic Stem Cells Research Centre. This research fundamentally promotes healthcare and regenerative medicine.
KEY TAKEDOWN
How to reverse aging naturally?
We can control the levels of the protein AP2A1 could naturally reverse aging effects at the cellular level.
Here’s how:
- Lowering AP2A1 levels in old cells rejuvenated them, making them behave like young cells again.
- Suppressing AP2A1 reduced cell size, reorganized their structure, and restored youthful characteristics.
- Blocking AP2A1 also improved cell adhesion and collagen support, both of which decline with age.
The secret to reversing cellular aging could be contained in a protein that switches cells between a “young” and an “old” state
This is the finding of researchers at the University of Osaka, who tested the expression of the protein “AP2A1” in cells of various ages.
“The findings were quite interesting,” bioengineering professor Shinji Deguchi, a co-author of the paper, said in a statement.
“Inhibition of AP2A1 in older cells restored youthfulness and induced cellular renewal, while overexpression of AP2A1 in young cells accelerated senescence,” he said.
With age, less active and larger cells start building up in several organs.
The “senescent” cells are both much larger than young cells and differ in their organization of stress fibers—the cell structure that aids them in moving around and interacting with the environment
We still aren’t sure how these senescent cells manage to keep such a massive size,” said the lead study author and bioengineer Pirawan Chantachotikul.
One that is very much a clue is that in senescent cells stress fibers are of greater thickness which in turn indicates that proteins in these structures play a role in their maintenance which is what we saw, she added. To look at this in their research the team looked at the AP2A1 protein which they noted has a higher level of expression in the stress fibers of senescent cells. We cultured human Fibroblasts (which are cells that give support to tissues) and epithelial cells (which line the inside and outside of the body including the skin) in the lab.
They subsequently blocked the creation of AP2A1 in older cells and overexpressed the protein in younger cells to observe effects that could have on aging-like behaviors.
The researchers discovered that AP2A1 seemed to be responsible for switching cells between their “young” and “old” states—senescent cells were rejuvenated by the suppression of the protein, and younger cells aged by its overexpression.
The scientists also found that the AP2A1 was frequently in close proximity to another protein: integrin β1, which aids cells in binding to the collagen scaffold that envelops them. Both proteins, the researchers described, travel along stress fibers within cells.
Additionally, integrin β1 is observed to enhance cell-substrate adhesions in fibroblasts, which could provide an explanation for the increased thickness of stress fibers in older cells.
“Our results indicate that senescent cells also retain their huge size by increased adhesion to the extracellular matrix through AP2A1 and integrin β1 transport along expanded stress fibers,” said Chantachotikul.
The association of AP2A1 with senescent cells, according to the researchers, indicates the protein can serve as a cellular aging marker.
The group also thinks that the results might provide a novel target for new treatments of age-related diseases.
Reference
Chantachotikul, P., Liu, S., Furukawa, K., & Deguchi, S. (2025). AP2A1 modulates cell states between senescence and rejuvenation. Cellular Signalling, 127. https://doi.org/10.1016/j.cellsig.2025.111616
