Immune response in the elderly can start normal, but struggle to switch off

The Gilroy Group of researchers at UCL, in collaboration with Professor Arne Akbar and AstraZeneca, have found that ‘immune responses in the elderly can start normally, but struggle to switch off’.

The UCL faculty of Medical Science has been looking at immune systems within the elderly, and why aging affects the immune system to become less able to defend the body against disease and infection.

‘As we age, our immune system, which protects us from infection, cancer and injury, becomes less effective. But why this happens is unclear.’

The findings from the immune system study have been published in ‘Nature Immunology’.

The findings show that macrophages – ‘the immune cells that clean up organs during immune responses’ – had ‘lost their ability to eat dead and dying cells.’

According to the researchers, a loss of appetite ‘causes a build-up of immunological debris’ that prevents wounds from healing.

A molecule called p38 was discovered by the researchers, which is an important regulator of cell function, was ‘perpetually activated in macrophages from older people rendering them less able to eat.’

Losmapimod was administered by the researchers, which is a drug provided by GlaxoSmithKline to target p38 molecules in the elderly.

The results showed improved macrophage function ‘allowing immunological debris to be cleared and ultimately rejuvenated the immune response’ in the elderly.

‘This is the first-time researchers have successfully reversed a novel defect in resolution biology, highlighting the tractability of targeting immune resolution to treat autoimmunity and chronic inflammatory conditions.

Prof. Gilroy said:

“Our findings help to explain why immune responses take longer to heal in older people.

“The immediate application of these findings and our next programme of research is to investigate the use of p38 inhibitors to accelerate delayed wound healing, a common complication of old age.

“Additionally, we think targeting p38 in wound healing has merit in diseases such as cancer and metabolic diseases. We are excited to explore this further.”