[GRG] using p38 MAPK inhibitors to rejuvenate old T cells


Contact: Chris Melvin
Biotechnology and Biological Sciences Research Council

Are you as old as what you eat? Researchers learn how to rejuvenate
aging immune cells

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,

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,


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://ift.tt/1rtT2E3. Please note this video will be
unlisted until the embargo lifts and should not be shared
publically until that time.


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:

About UCL (University College London)

Founded in 1826, UCL was the first English university established
after Oxford and Cambridge, the first to admit students regardless
of race, class, religion or gender, 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
almost 29,000 students from 150 countries and in the region of
10,000 employees. Our annual income is more than £900 million.
http://www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our
YouTube channel YouTube.com/UCLTV

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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