Science
Inhibiting specific immune receptor reduces signs of aging across organs in mice
Stanford researchers found that blocking the EP2 receptor restores the ability of immune cells to clear inflammatory neutrophils, improving physical and cognitive markers in aging mice.
The short version
- Stanford Medicine researchers identified that tissue-resident macrophages lose their ability to clear aged, inflammatory neutrophils over time, partly driven by the inflammatory hormone receptor EP2.
- Genetically deleting or pharmacologically blocking EP2 in mouse macrophages maintained youthful organ function, reduced chronic inflammation, and preserved memory and muscle strength.
- Analysis of human liver datasets revealed matching age-related trends of EP2 elevation and neutrophil accumulation.
- No approved drug currently exists to selectively target EP2, making the development of safe, targeted human therapeutics the next primary challenge.
Key facts
- A study published in Science by Stanford Medicine researchers found that aging tissue-resident macrophages decline in their ability to clear senescent neutrophils due to inflammatory signaling via the EP2 receptor.[ScienceDaily]
- Genetically deleting EP2 specifically in tissue-resident macrophages of older mice preserved youthful levels of 59 out of 71 age-altered blood proteins and protected against frailty, excess visceral fat, and cognitive decline.[ScienceDaily]
- Treating 22-month-old normal mice with an experimental EP2-inhibiting compound for two months restored total and senescent neutrophil counts toward youthful baselines.[ScienceDaily]
- The researchers observed comparable patterns of elevated EP2 activity, reduced macrophage clearance function, and senescent neutrophil accumulation in human liver cell data.[ScienceDaily]
What remains uncertain
- Whether selective EP2 inhibition will safely and effectively slow age-related decline in humans remains unproven, as no approved selective EP2-inhibiting drugs currently exist and human data remains limited to cell observations.[ScienceDaily]
Sources
- One immune switch may help drive aging across the bodyScienceDaily - Health