Key Takeaways
- A study found that restoring the body's ability to remove senescent cells could prevent cognitive decline and frailty in older mice.
- Senescent neutrophils, normally cleared by macrophages, accumulate with age due to increased prostaglandin E2 activity.
- Blocking EP2 receptor activity improved signs of ageing, including reduced inflammation and better mobility.
A groundbreaking study has shown that restoring the body's ability to remove senescent cells could significantly combat age-related decline. Senescent cells are those that have stopped dividing but continue to secrete harmful substances, potentially turning other cells rogue. These cells accumulate as we age and can contribute to various signs of frailty and cognitive decline.
Researchers from Stanford University compared younger mice (aged 6-8 months) with older ones (23-25 months), finding that the latter had a higher presence of senescent neutrophils in their organs, including the liver, spleen, and bone marrow. Neutrophils are typically the body's first line of defence against infection but become problematic as they accumulate without being cleared.
The study identified prostaglandin E2 (PGE2) as a key factor in this process. PGE2 activity increases with age, overstimulating the EP2 receptor on tissue-resident macrophages, which are responsible for removing damaged cells and debris. This leaves them less capable of clearing senescent cells.
To test their hypothesis, the researchers genetically modified older mice to block EP2 activity in tissue-resident macrophages. These animals showed significant improvements in signs of ageing, including lower levels of inflammation, reduced muscle loss, less visceral fat, and better mobility. They also performed almost as well as younger mice in memory tests.
The team further tested an experimental drug that blocks the EP2 receptor. When given orally to older mice for two months, this drug caused similar improvements to those seen in genetically modified animals. This suggests a potential therapeutic approach to combat age-related decline through pharmacological means.
While the study is promising, researchers caution that EP2 is part of a normal signalling system and blocking it could have unintended consequences. Derek Gilroy from University College London noted, 'What’s attractive about this study is that it is not trying to kill senescent cells directly but repairing the body's own waste-disposal system.'
The findings open up new avenues for research into age-related diseases and suggest a potential method to maintain cognitive sharpness and physical health as we grow older. However, more studies are needed to confirm these results in humans.
'What’s attractive about this study is that it is not trying to kill senescent cells directly but repairing the body's own waste-disposal system.'
Derek Gilroy, University College London
