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Researchers reveal molecules responsible for ageing in immunity cells

Copyright: NIAID on Flickr by CC 2.0
News from: University College London
News from: Wellcome Trust

As we age our immune system declines – but is it possible to reverse the weakening immune cells while growing old?

According to a recent study, supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust, published in Nature Immunology it may be accomplished. Researchers from University College London (UCL) and University of Oxford have discovered a key to boost immune cells during the ageing process in both humans and mice by blocking a group of proteins called sestrins.

“Our life expectancy at birth is now twice as long as it was 150 years ago and our lifespans are on the rise. Healthcare costs associated with ageing are immense and there will be an increasing number of older people in our population who will have a lower quality of life due in part to immune decline,” said Professor Arne Akbar Head of the Immunosenescence Research Group, UCL.

For all living organisms, the ageing process affects immune system cells known as ‘T lymphocytes’ which are controlled by a molecule called ‘p38 MAPK’ – this molecule acts like a brake that prevents certain cellular functions. The brake-like molecule is activated by signals that sense low nutrient levels or those related to the ageing process. The researchers explored if the braking action could be reversed by using an inhibitor.

They tested their theory by inhibiting protein molecules, also known as sestrins, which act upstream of p38 activation in T lymphocytes. The sestrins formed a molecular complex termed sMAC , a sestrin-induced MAPK activation complex with p38 and also two other classes of MAPKs, ERK and JNK. The activation complex provided a way for synching all three classes of MAPK within a single cell type. The blocking of the complex, in human T cells and also in genetically modified mice that lack the sestrins, revealed an enhanced function of T lymphocytes.

“MAPK pathways have been studied for nearly thirty years. The discovery of the sMAC illuminates a very different mode of MAPK activation, introducing the possibility of new forms of immunotherapy. How the sMAC feeds into metabolic and pathophysiological processes will be important to examine in the future,” said Dr Alessio Lanna, UCL Infection & Immunity and Nuffield Dept. of Medicine, Oxford University.

“We’re on the cusp of boosting immunity in old animals, and possibly in old humans as well. It’s now essential we identify safe ways to counteract some of these deleterious changes in the immune system during ageing”, said Professor Akbar.

“With an ageing population it is imperative we understand the biological basis of ageing in order to support lifelong health and wellbeing,” said Professor Melanie Welham, Chief Executive, BBSRC. “This research demonstrates how immune enhancement is possible.”


Notes to editors

The paper A sestrin-dependent Erk–Jnk–p38 MAPK activation complex inhibits immunity during aging is published in Nature Immunology.


BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by government, BBSRC invested £473 million in world-class bioscience, people and research infrastructure in 2015-16. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

More information about BBSRC, our science and our impact.
More information about BBSRC strategically funded institutes.

About Wellcome Trust

Wellcome exists to improve health for everyone by helping great ideas to thrive. We’re a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate.

About University College London

University College London (UCL) was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 38,000 students from 150 countries and over 12,000 staff. Our annual income is more than £1Bn. | Follow us on Twitter @uclnews | Watch our YouTube channel

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Tags: health human health ageing University College London Wellcome Trust immunity press release