Summary: Scientists have identified AP2A1, a key protein that may retain a secret that reverses cell aging. This study found that suppressing AP2A1 in older cells leads to rejuvenation, and overexpressing it in younger cells promotes aging. This protein interacts with integrin β1, strengthens cell adhesion and contributes to the enlarged structure of senescent cells.
By manipulating AP2A1, researchers can develop new treatments to combat potentially age-related diseases and improve skin health. The findings provide new insight into how stress fibers affect cell size and aging. AP2A1 serves as a biomarker of aging and as a target for treatments aimed at slowing or reversing the aging process.
Important facts:
Senescence proteins have been identified: AP2A1 plays an important role in maintaining the expanded structure of senescent cells. Repeated Aging: Inhibition of AP2A1 rejuvenates older cells.
Source: Osaka University
There are numerous products available for sale that promise an eternal youth look by erasing wrinkles and creating jaw lines. But what if we could really turn back time at the cellular level? Now, Japanese researchers have found a protein that could do just that.
In a study published this month in Cell Signaling, researchers at Osaka University revealed that key proteins are responsible for switching between “young” and “old” cell states.
As we age, there are fewer older active cells known as senescent cells, which accumulate in multiple organs. These cells are significantly larger than younger cells, indicating altered tissues of stress fibers. This is the structural part of the cell that helps to interact with the environment.
“We still don’t understand how these senescent cells can maintain their huge size,” says the lead author of the study’s Pirawan Chantachotikul.
“One interesting cues are that stress fibers are much thicker in senescent cells than in younger cells, suggesting that the proteins within these fibers help support size.”
To investigate this possibility, researchers looked at AP2A1 (adapter protein complex 2, alpha1 subunit). AP2A1 is a protein upregulated by stress fibers in senescent cells, including fibroblasts, which create and maintain the structural and mechanical properties of the skin.
The researchers ruled out AP2A1 expression in older cells and overexpressing AP2A1 in younger cells to determine its impact on aging-like behavior.
“The results were very interesting,” explains senior author Deguchi Island. “Suppression of AP2A1 in older cells reversed aging and promoted cell rejuvenation, while overexpression of AP2A1 in younger cells promoted aging.”
Furthermore, the researchers found that AP2A1 is often closely related to integrin β1. This is a protein that helps cells latch cells into collagen matrices like the scaffold surrounding them, and we found that both AP2A1 and integrin β1 migrate along stress fibers within the cell.
Furthermore, integrin β1 enhanced cell-assisted adhesions in fibroblasts. This may explain the cause of the raised or thickened structure characteristic of senescent cells.
“Our findings suggest that senescent cells maintain large size by improving adhesion to the extracellular matrix via the movement of expanded β1 along the expanded stress fibers,” Chantachotikul concludes.
Given that AP2A1 expression is very closely related to signs of senescent cells, it may be used as a marker of cell senescence. The research team’s work could also provide new therapeutic targets for diseases associated with geriatric age.
About this genetics and aging research news
Author: Saori Obayashi
Source: Osaka University
Contact: saori obayashi – Osaka University
Image: Image credited to Neuroscience News
Original research: Open access.
“AP2A1 “regulates cellular state between aging and rejuvenation” by Pirawan Chantachotikul et al.
Abstract
AP2A1 regulates cellular state during aging and rejuvenation
Aging progresses with the accumulation of senescent cells in multiple organs. These cells increase in size compared to younger cells, further promoting aging and age-related diseases.
The molecular mechanisms behind the maintenance of such giant cellular architecture, currently undergoing aging, are not well understood.
Here we focus on the replication and senescence-induced actin stress fiber reorganization in human fibroblasts, which is widely used as a senescent cell model.
Along with previous proteomic studies, we identified AP2A1 (alpha-1 adaptive subunit of adaptor protein 2) as upregulated in senescent cells along the length of expanded stress fibers.
Knockdown of AP2A1 reversed the senescence-related phenotype and showed cell rejuvenation characteristics, while overexpression in young cells progressed the senescence phenotype.
Similar functions of AP2A1 were identified in UV or drug-induced aging and were similarly observed in epithelial cells. Furthermore, AP2A1 colocalizes with integrin β1, and we found that both proteins migrate linearly along the stress fibers.
With the observation that focal adhesions are enlarged in senescent cells, which is consistent with enhanced cell adhesion to the substrate, these results suggest that senescent cells can provide effective anchorage via integrin β1 translocation along the stress fibers. It suggests that strengthening will help maintain a larger size.
This mechanism is more efficient in senescent cells compared to cases that rely on random diffusion of integrin β1, given the expansion of cell size and increased travel time and distance of endocytic vesicle transport. It may work.
