Transcriptome analysis of age-, gender- and diet-associated changes in murine thymus

Abstract

The loss of thymic function with age may be due to diminished numbers of T-cell progenitors and the loss of critical mediators within the thymic microenvironment. To assess the molecular changes associated with this loss, we examined transcriptomes of progressively aging mouse thymi, of different sexes and on caloric-restricted (CR) vs. ad libitum (AL) diets. Genes involved in various biological and molecular processes including transcriptional regulators, stress response, inflammation and immune function significantly changed during thymic aging. These differences depended on variables such as sex and diet. Interestingly, many changes associated with thymic aging are either muted or almost completely reversed in mice on caloric-restricted diets. These studies provide valuable insight into the molecular mechanisms associated with thymic aging and emphasize the need to account for biological variables such as sex and diet when elucidating the genomic correlates that influence the molecular pathways responsible for thymic involution.

Caloric restriction

“…CR delays thymic involution in mice (Jolly, 2004;Yang et al, 2009;Lustig et al, 2007) and also decreases the production of PGE 2 (Meydani et al, 1990). As anticipated this leads to greater T lymphocyte production and activity in later life, and to a reversal of the age related reduction in IL-2 production in mice under CR.…”

Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse

“…Conclusions generated from previous investigations conflict regarding the association between the effects of CR and aging. On the one hand, an early investigation revealed that age-associated expression patterns in muscle were "either completely or partially prevented by caloric restriction" [19], and this conclusion was supported in subsequent studies [14,20,21]. Other investigations, however, have yielded different conclusions.…”

Aging of the Immune System as a Prognostic Factor for Human Longevity

“…It is likely that, given the complexity of immune system development, the number of cells involved in an immune response (and especially the changes in the immune system with aging), multiple genetic loci, and many genes will contribute to agerelated changes in immunity (46). Furthermore, recent studies investigating the molecular mechanisms associated with thymic aging showed the necessity of taking biological variables such as gender and diet into account when studying the role of genomics in the molecular pathways responsible for thymic involution (62). The use of model organisms facilitates testing different hypotheses regarding the role of genetics in immune responses.…”