Role of Integrin Beta 3 in Aging Cells May Lead to New Aging, Early Cancer Treatments

Integrin beta 3 (β3) regulates cellular senescence by activating the TGF-β pathway, a study published in Cell Reports found. These findings may lead to new treatments for aging and early cancer.

Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells; however, the precise mechanism regulating senescence was unknown.

Organs and tissues are formed by cells that coordinate their actions to help a body function correctly. However, prior findings show a small number of abnormal cells in tissues derived from older patients and at the initial stages of cancer undergo senescence, which is believed to affect tissue function.

The senescent cells do not proliferate, but can communicate with neighboring cells, primarily through the release of inflammatory proteins.

In a study using human primary fibroblasts and fibroblasts cells derived from young and older human donors, the investigators found senescent cells communicate in a different way, via the expression of integrin membranes. This includes β3, which is highly expressed during senescence.

“This is the first time that integrin beta 3 has been identified in the context of senescence and aging, and could be in the future a potential therapeutic target during early carcinogenesis and aging,” said lead investigator Dr Ana O’Loghlen. “This finding is particularly interesting, as there is actually a drug against integrin beta 3, called ‘cilengitide’, that averts one of the disadvantages of aging in our model—–inflammation. It does this without increasing cell proliferation, which is an advantage, as an increase in cell proliferation imposes a risk for cancer.”

The findings indicated how β3 is regulated and the signaling mechanism it uses to transmit senescence to surrounding cells. Furthermore, investigators found that β3 was upregulated in a subset of tissue from mice.

“We provide evidence from the β3 subunit being a marker and regulator of senescence,” the authors wrote. “Our results demonstrate the importance of FA complex formation regulating the microenvironment during senescence activation and identify integrins as potential therapeutic targets to promote healthy agents.”