Unknown protein found to drive cellular aging
A protein that barely appears in the scientific literature turns out to play a direct role in cellular aging. That is an unexpected finding in a field that has studied the same familiar players for decades.
Cellular senescence is the process by which damaged cells stop dividing but remain active and release inflammatory substances. This is useful as a temporary response to damage, but harmful when those cells accumulate. Researchers looking for new proteins that drive this process came across PTCHD4.
What does PTCHD4 do?
PTCHD4 is structurally related to a protein involved in the Hedgehog signaling pathway, a cell communication system that regulates growth and repair. But the specific function of PTCHD4 was previously unknown. That has now changed.
Cells that do not produce PTCHD4 aged later in the lab than normal cells: on average at passage 14 rather than passage 8. Cells with extra PTCHD4 aged earlier, already at passage 5, according to the researchers. In living mice, animals without this protein were more resistant to a substance that mimics aging and lived naturally months longer. No harmful side effects from the absence of the protein were detected.
What makes this different from other senescence studies?
Most senescence research focuses on established mechanisms, such as the p16 protein or SASP (the package of inflammatory substances secreted by senescent cells). PTCHD4 sits outside those established pathways. The protein is barely present in cells under normal conditions, but increases with damage and aging. Human tissue from patients with idiopathic pulmonary fibrosis, a serious lung disease, contained more PTCHD4 than healthy tissue.
These are early findings, primarily from cell and animal studies. Their relevance for humans has yet to be established. But PTCHD4 represents a concrete and novel target in senescence research, and that is rare.
Search terms to explore further: cellular senescence SASP mechanisms, Hedgehog signaling pathway aging, senescence biomarkers p16 SA-beta-gal