Edinburgh Napier University

  Cellular senescence is a state of permanent cell cycle arrest in which a cell is unable to further divide in response to normal growth stimuli. Telomere shortening, believed to be a mechanism of cellular senescence, is a result of numerous rounds of cell division and can be accelerated by heightened levels of oxidative stress. An accumulation of senescent T lymphocytes in blood and tissues has been suggested to contribute to the general immunosuppression seen in the elderly. Obese individuals and athletes taking part in regular high intensity exercise are subjected to heightened states of oxidative stress which appears to result in immunosuppression and increased susceptibility to infection. It was hypothesised that there would be an accumulation of senescent T lymphocytes with ageing, with obesity and during six months training for an Iron man competition.

Senescent CD4+ and CD8+ T peripheral blood lymphocytes were identified by 4 colour flow cytometry, based on their cell surface expression of CD57, the killer cell lectin-like receptor G1 (KLRG1) and the lack of cell surface expression of CD28. Where telomere length measurements were performed, CD4+ and CD8+ T lymphocyte subsets were isolated and telomere lengths were compared to the proportions of KLRG1+, CD57+ and CD28+ cells in each subset.

Older subjects and obese subjects had significantly larger proportions of senescent cells (KLRG1+/CD57+) in the CD8+ but not the CD4+ peripheral blood T lymphocyte subset. Furthermore, during six months training for an Iron Man competition, compared to the first month, club level athletes showed a 92% increase in the frequency of senescent cells (KLRG1+/CD57+) in the CD4+ but not the CD8+ T lymphocyte subset. Telomere length was negatively correlated with the proportion of KLRG1+ and CD57+ cells and positively correlated with the proportion of CD28+ cells in the CD4+ but not the CD8+ T lymphocyte subset.

It is concluded from this work that KLRG1+/CD57+ senescent T lymphocytes accumulate with age, obesity and regular high intensity training, which may contribute to the increased immunosuppression associated with these states.