Researchers identify a receptor that may contribute to the aging of kidney immune cells and show that blocking it can improve kidney health in mice

Researchers have identified a potential new way to reduce the effects of aging on the kidneys by targeting a receptor found on immune cells called macrophages.

The study found that as macrophages become senescent, a state in which damaged or stressed cells stop dividing but continue releasing inflammatory signals, they produce increasing amounts of a receptor known as P2RX7.

Senescent cells normally develop throughout life as a result of damage and stress. In younger people, the immune system generally removes these cells efficiently. With age, however, senescent cells can accumulate and contribute to chronic inflammation and tissue damage.

The researchers focused on macrophages, immune cells that play an important role in protecting tissues and repairing damage. They examined kidney tissue using single-cell RNA sequencing and tracked changes in macrophages over time in mice with kidney injury.

Their analysis showed a steady increase in P2RX7 on macrophages as the cells moved toward a senescent state.

The researchers then tested a small molecule designed to block P2RX7. In both mice with kidney injury caused by sepsis and older mice, blocking the receptor was associated with improved kidney function, reduced tissue damage and lower levels of macrophage senescence.

The treatment also appeared to improve the ability of senescent repair-related macrophages to migrate, multiply and participate in wound healing. These changes were linked to reduced inflammation and improved tissue repair.

The findings suggest that P2RX7 may play an important role in the accumulation and harmful effects of senescent macrophages in aging and injured kidneys.

While the research was conducted in mice and does not establish that the approach will work in humans, it points to P2RX7 as a possible target for future treatments aimed at kidney injury and age-related decline.

The researchers say their findings provide a potential therapeutic strategy for conditions in which immune-cell aging contributes to kidney damage.