Changes in immune cell subtypes during ageing.

BACKGROUND: The immune system comprises many different types of cells, each with different functions and properties during immune defence. The numbers and types of immune cells in the circulation is highly dynamic and regulated by infections, ageing and certain types of cancers. It is recognised that immune function decreases during ageing, but the biological age at which these functional changes occur is variable, and how ageing affects the different sub-types of lymphocytes, monocytes and NK cells in the circulation is not fully defined. METHODS: In this study, we recruited 24 healthy volunteers over the age range of 23y to 89y and measured the numbers of different subclasses of circulating cells by immuno-phenotyping and flow cytometry. RESULTS: We show increased monocyte:lymphocyte ratios in a > 50y cohort and most T cell subsets were decreased, except for CD4+ cells, which were increased in this cohort. In addition, there was NK cell expansion and increased HLA-DR+ T cells, but decreased numbers of classical monocytes and increased numbers of CD4+ monocytes in this >50y cohort. CONCLUSIONS: These data indicate that healthy ageing is associated with changes in both the major cell groups but also individual subclasses of cells, and these are likely to result from continuous immune challenge and impaired development.

Upregulation of p16INK4A in Peripheral White Blood Cells as a Novel Screening Marker for Colorectal Carcinoma.

OBJECTIVE: Screening of colorectal cancer (CRC) is important for the early detection. CRC is relating to aging and immuno-senescence. One such senescent marker is p16INK4A expression in immune cells. The objective of the study is to investigate the protein expression of p16INK4A in peripheral white blood cells as a screening marker for colorectal cancer. METHODS: A case-control studies were conducted. Cases were patients with colorectal cancer and controls were matched with cases based on age and sex. Peripheral blood was collected from patients and controls and the protein p16INK4A was measured with immunofluorescent techniques. The p16INK4A levels from cases and controls were evaluated using ROC analysis to be used as a screening marker in CRC patients. Mean fluorescent intensity of p16INK4A of cases and controls were analyzed in CD45+, CD3+ or CD14+ cells. The p16INK4A levels of cases were also correlated with clinical data. RESULT: Statistically significant increased expression of p16INK4A levels were found in cases compared to controls. p16INK4A in peripheral immune cells had 78% sensitivity and 71% specificity which can possibly be used as a diagnosis tool for colorectal cancer. P16INK4A-positive cell percentage and mean florescent intensity were significantly higher in CD45+ cells, CD3 positive cells and CD14 positive cells. No significant correlation was observed with the clinical data and p16INK4A level of CRC patients. CONCLUSION: The significant increase of p16 INK4A expression level in peripheral immune cells represents potential for use as a CRC screening marker.