Since the dawn of humanity, the quest for eternal youth has fueled myths and legends. From fountains of youth to miraculous elixirs, the idea of defeating the passage of time has always fascinated. While the promise of physical immortality remains in the realm of fiction, science today seems to be bringing us closer to a form of rejuvenation, not at the individual level, but at the cellular level.
Researchers at Osaka University in Japan may have unlocked the secret of cellular aging. Their work, published in the journal
Cellular Signaling, reveals the key role of a protein, AP2A1, in the senescence process. This discovery paves the way for treatments that could reverse the effects of time on our cells, and consequently, on our entire organism.
AP2A1: The conductor of cellular aging?
With age, our cells undergo transformations. Some become senescent, meaning they stop dividing and lose their functions. These cells, larger than young cells, exhibit changes in their "stress fibers," structures that allow them to move and interact with their environment. Scientists are seeking to understand how these senescent cells manage to maintain their imposing size.
The team at Osaka University focused on the protein AP2A1. This protein, present in greater quantities in the stress fibers of senescent cells, could play a key role in cellular aging. To test this hypothesis, the researchers modulated the expression of the AP2A1 protein in young and old cells.
The results of these experiments were surprising. Suppressing the expression of AP2A1 in old cells led to a reversal of senescence and cellular revitalization. Conversely, increasing the expression of AP2A1 in young cells accelerated the senescence process. These observations suggest that AP2A1 acts as a switch between the "young" and "old" states of cells.
Interaction with integrin β1
The researchers also discovered that AP2A1 closely interacts with another protein, integrin β1. The latter allows cells to anchor to the extracellular matrix, a network of proteins surrounding them. AP2A1 and integrin β1 move together along stress fibers. Integrin β1 strengthens cell adhesion to the substrate, which could explain the increased size of senescent cells.
The strong correlation between AP2A1 expression and cellular senescence makes it a promising candidate as a marker of cellular aging. Moreover, the active role of AP2A1 in the aging process opens the door to new therapeutic strategies to combat age-related diseases.
To go further: What is cellular senescence?
Cellular senescence is a state in which a cell stops dividing but does not die. It differs from apoptosis (programmed cell death) and necrosis (accidental cell death). Senescent cells are often larger than young cells and exhibit morphological changes, particularly in their cytoskeleton and organelles. They can remain metabolically active and secrete various molecules, such as inflammatory factors, growth factors, and extracellular matrix-degrading enzymes.
Cellular senescence can be triggered by various factors, such as DNA damage, telomere shortening (the ends of chromosomes), oxidative stress, oncogene activation, or extracellular signals. It is considered a protective mechanism against uncontrolled cell proliferation, particularly in cases of DNA damage that could lead to the formation of cancer cells. However, the accumulation of senescent cells in tissues can have detrimental effects on the organism, contributing to aging and the development of age-related diseases.
Senescent cells can have varying effects on surrounding tissues. In some cases, they can promote tissue repair and homeostasis. In other cases, they can contribute to chronic inflammation, fibrosis (excessive formation of connective tissue), and loss of organ function. The balance between the beneficial and harmful effects of cellular senescence depends on the context and the type of cells involved. Research on cellular senescence is booming, with the aim of better understanding its role in aging and diseases, and developing new therapeutic strategies to modulate its effects.
Article author: Cédric DEPOND