Researchers from UCL (University College London) have demonstrated how an interplay between nutrition, metabolism and immunity is involved in the process of ageing.

The two new studies, supported by the Biotechnology and Biological Sciences Research Council (BBSRC), could help to enhance our immunity to disease through dietary intervention and help make existing immune system therapies more effective.

As we age our immune systems decline. Older people suffer from increased incidence and severity of both infections and cancer. In addition, vaccination becomes less efficient with age.

In previous BBSRC funded work, Professor Arne Akbar's group at UCL showed that ageing in immune system cells known as 'T lymphocytes' was controlled by a molecule called 'p38 MAPK' that acts as a brake to prevent certain cellular functions.

They found that this braking action could be reversed by using a p38 MAPK inhibitor, suggesting the possibility of rejuvenating old T cells using drug treatment.

In a new study published today in Nature Immunology the group shows that p38 MAPK is activated by low nutrient levels, coupled with signals associated with age, or senescence, within the cell.

It has been suspected for a long time that nutrition, metabolism and immunity are linked and this paper provides a prototype mechanism of how nutrient and senescence signals converge to regulate the function of T lymphocytes.

The study also suggests that the function of old T lymphocytes could be reconstituted by blocking one of several molecules involved in the process. The research was conducted at UCL alongside colleagues from Complejo Hospitalario de Navarra, Pamplona, Spain.

The second paper, published in The Journal of Clinical Investigation, showed that blocking p38 MAPK boosted the fitness of cells that had shown signs of ageing; improving the function of mitochondria (the cellular batteries) and enhancing their ability to divide.

Extra energy for the cell to divide was generated by the recycling of intracellular molecules, a process known as autophagy. This highlights the existence of a common signaling pathway in old/senescent T lymphocytes that controls their immune function as well as metabolism, further underscoring the intimate association between ageing and metabolism of T lymphocytes.

This study was conducted by researchers from UCL, Cancer Research UK, University of Oxford and University of Tor Vergata, Rome, Italy.

Professor Arne Akbar said: "Our life expectancy at birth is now twice as long as it was 150 years ago and our lifespans are on the increase. 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. It is therefore essential to understand reasons why immunity decreases and whether it is possible to counteract some of these changes.

"An important question is whether this knowledge can be used to enhance immunity during ageing. Many drug companies have already developed p38 inhibitors in attempts to treat inflammatory diseases. One new possibility for their use is that these compounds could be used to enhance immunity in older subjects. Another possibility is that dietary instead of drug intervention could be used to enhance immunity since metabolism and senescence are two sides of the same coin."

###

Notes to editors

Contact: Chris Melvin, BBSRC media officer, 01793 414694, chris.melvin@bbsrc.ac.uk

References:

The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells by Lanna et al is published in Nature Immunology.

The study was funded by BBSRC and the Medical Research Council.

p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells by Henson et al is published in The Journal of Clinical Investigation.

The study was funded by BBSRC, the Medical Research Council, National Institute for Health Research, Wellcome Trust, Lady Tata Memorial Trust and Cancer Research UK.

Video: A UCL video about the research can be viewed at: http://youtu. be/ oQ-unC7D9i4 . Please note this video will be unlisted until the embargo lifts and should not be shared publically until that time.

About BBSRC

The Biotechnology and Biological Sciences Research Council (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 over £484M in world-class bioscience in 2013-14. 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. For more information about BBSRC, our science and our impact see: http://www. bbsrc. ac. uk For more information about BBSRC strategically funded institutes see: http://www. bbsrc. ac. uk/ institutes

About UCL (University College London)