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Title: Age-Associated Alterations in the Murine Thymus
Author: Aw, Danielle Pei Shan
ISNI:       0000 0001 3433 5296
Awarding Body: Royal Veterinary College (University of London)
Current Institution: Royal Veterinary College (University of London)
Date of Award: 2008
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The immune system progressively declines with age, which is associated with an increase in susceptibility and severity of infections, cancers and autoimmune diseases. Of all alterations, involution of the'thymus is the most dramatic and ubiquitous resulting in decreased exportation of na'ive T cells. This is linked with constriction of T cell diversity, alterations in their phenotype and function and corrosion of telomeres due to replicative senescence. These changes are believed to be a major driving factor in immunosenescence. The precise mechanisms regulating thymic atrophy remain obscure, with several hypotheses implicating extrinsic and intrinsic factors. In order to elucidate possible mechanisms an intensive examination of the phenotypical and functional transformations in the thymic microenvironment and alterations of thymocytes in the murine thymus with age was undertaken. There were no significant changes in the proportion of the major subpopulations (as based on CD4 and CDB), but a significant decline in expression of key molecules CD3 and CD24, This is accompanied by a general decrease in the ability of thymocytes from older mice to respond to activation with broad or more specific mitogens and a concurrent increased resistance to induced apoptosis. Thymic epithelial cells (TEC) are attributed as the crucial instructors of thymopoiesis, thus the affect of ageing on TEC was investigated. A substantial age-dependent decay of defining TEC molecules was observed in the murine thymus. This is simultaneous to a disorganisation of the thymic compartments, a morphological transformation within the epithelial cells and alterations of the archetypal staining patterns. Furthermore, this is paralleled with the novel finding of increased senescence in the thymus of older mice. Consequently, thymic involution may be the result of the deteriorating thymic microenvironment, instigating aberrant thymopoiesis, thus exacerbating the deficiencies in both the thymus and periphery.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available