Cranfield University

Professor Richard Aspinall

Professor of Translational Medicine
Location: Cranfield Health, Vincent Building, Cranfield Campus
E: r.aspinall@cranfield.ac.uk
T: +44 (0)1234 758343

Current activities

Much of my work in the last few years has been on immunodeficiency with a particular emphasis on the effect of age.

One strand of the work has been on age associated immunodeficiency working with the hypothesis that age related immune dysfunction follows atrophy of the thymus. My approach to overcome this problem has been to identify the causes of thymic atrophy and from there to determine a rational intervention therapy which would reverse thymic atrophy, increase thymic output and lead to improved immunity. Using animal models I have shown that age associated atrophy of the thymus was due to a bottleneck at very early stages in the intrathymic T cell developmental pathway. In a series of experiments my group showed that thymic stem cells from old animals have the same capacity for differentiation as those from young animals suggesting that the problem was associated with the stromal elements of the thymus. Analysis of thymic epithelial cells revealed that the amount of interleukin 7 (IL-7) they produced declined with age. Injection of IL-7 into old mice reversed thymic atrophy and induced the production of new T cells and improved the immune response. Proof of principle trials in elderly non-human primates supported this hypothesis showing that IL-7 may be beneficial in improving immunity in the elderly. However, too much IL-7 may be deleterious especially when localised. Recent work suggests that high levels of Il-7 within the joint may contribute towards the pathology of Rheumatoid Arthritis and we are currently funded through an EU FP7 consortium called Masterswitch to assess this problem.

A second strand of the work has been to determine the effect of nutrition on the development of the immune system in the offspring. We were the first to show that IL-7 was present in maternal milk during the immediate post partum period and suggested it plays a significant role in the development of the thymus in the offspring. Work had already shown that season of birth predicts longevity with those born before the major harvest in January having a shorter lifespan than those born after the harvest. The high incidence of deaths following infection in those born before the harvests suggests some programming of the immune system. Our work in the Gambia revealed that thymic output in infants born after the harvest was higher compared with those born before the harvest, and this linked with a second finding that IL-7 was present in breast milk at levels which were higher after the harvest. The effect of nutrition on the immune response is continuing through collaborative work with Dr Parveen Yaqoob at the University of Reading on a grant from the BBSRC on the Immunomodulatory effects of pre- and probiotics.

Reversal of thymic atrophy seems a viable option but the timing of when such a procedure should begin would be critically dependant on a number of factors including the health status of the individual. Through an EU FP7 consortium called Markage we are seeking biomarkers of ageing which may help with determining the immune status of an older individual. Once we can identify individuals who would benefit from this therapy we became aware that there may be problems with compliance. Many individuals do not like injections and so injection of IL-7 may not be the best way of delivering a therapeutic agent. To overcome this problem we have funding from Research into Ageing to look at other routes of delivery.  As an alternative approach we are actively pursuing how stem cells can be used to repair and regenerate damaged or diseased organs and investigating techniques to regenerate the aging thymus by the application of stem cells in a study funded by the Myrtle Peach Trust .

The identification of older individuals presenting with infection is often fraught with difficulty. Unlike younger individuals where the presenting signs are a rise in body temperature accompanied by sweating, lethargy and an increased respiration rate, presentation in older individuals is frequently blunted and atypical. This is an issue which can be approached through telemedicine and the production of remote monitoring devices and we are active in this area in conjunction with Prof Alan Sinclair and the University of Bedfordshire.

Clients

BBSRC, MRC, Research into Ageing

Background

My interests centre on defining a therapeutic approach to age associated immune deficiencies. My first degree was from Bristol University and my Ph.D was from Birmingham University. On completion I taught Anatomy for a year and then moved to Oxford University and from there was appointed Senior Scientific Officer at the Institute of Animal Physiology in Cambridge. Whilst there I was asked to join a startup biotechnology company and after four years in the company I moved to Charing Cross and Westminster Medical School to become a lecturer in Immunology. I became a Senior Lecturer and subsequently Reader in Immunology at Imperial College London and was recently appointed Professor in Translational Medicine at Cranfield University and a Visiting Professor at the Open University. I am a member of the British Society for Immunology, the British Transplantation Society and also the British Society for Research on Ageing and was a member of MRC College of Experts. In addition I have served on the editorial boards of the journals ‘Mechanisms of Ageing and Development’ and also ‘Biogerontology’, I am a section editor on ‘Immunity and Ageing’ an associate editor for Current Gerontology and Geriatrics Research and a Board member for the Bedfordshire and Hertfordshire Postgraduate Medical School. Until recently I was Chairman of the British Society for Research on Ageing.

Selected publications

• Lang PO, Govind S, Mitchell WA, Siegrist CA & Aspinall R. (2011) Vaccine effectiveness in older individuals: What has been learned from the influenza-vaccine experience, Ageing research reviews, 10 (3) 389-395. (Link to DOI)
• Aspinall R, Prentice AM & Ngom PT. (2011) Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T-Cell Development in Offspring, PLoS ONE, 6 (6). (Link to DOI)
• Ngom PT, Solon J, Moore SE, Morgan G, Prentice AM & Aspinall R. (2011) Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden, Journal of Biomedical Science, 18 (41). (Link to DOI)
• Lang PO, Govind S, Michel JP, Aspinall R & Mitchell WA. (2011) Immunosenescence: Implications for vaccination programmes in adults, Maturitas, 68 (4) 322-330. (Link to DOI)
• Mitchell WA, Lang PO & Aspinall R. (2010) Tracing thymic output in older individuals, Clinical and Experimental Immunology, 161 (3) 497-503. (Link to DOI)
• Lang PO, Govind S, Mitchell WA, Kenny N, Lapenna A, Pitts D & Aspinall R. (2010) Influenza vaccine effectiveness in aged individuals: The role played by cell-mediated immunity, European Geriatric Medicine, 1 (4) 233-238. (Link to DOI)
• Aspinall R & Goronzy JJ. (2010) Immune senescence, Current Opinion in Immunology, 22 (4) 497-499. (Link to DOI)
• Lang PO, Mitchell WA, Lapenna A, Pitts D & Aspinall R. (2010) Immunological pathogenesis of main age-related diseases and frailty: Role of immunosenescence, European Geriatric Medicine, 1 (2) 112-121. (Link to DOI)
• Aspinall R, Pitts DG, Lapenna A & Mitchell JB. (2010) Immunity in the Elderly: The Role of the Thymus, Journal of Comparative Pathology, 142 (1) 111-115. (Link to DOI)
• Monto AS, Aspinall R, Mcelhaney JE, Montao LF, Nichol KL, Puig-Barber J & Stephenson I. (2009) Influenza control in the 21st century: optimizing protection of older adults, Vaccine, 27 (37) 5043-5053. (Link to DOI)
• Siegrist CA & Aspinall R. (2009) B-cell responses to vaccination at the extremes of age, Nature Reviews Immunology, 9 (3) 185-94. (Link to DOI)

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