Levels of DNA damage have been shown to increase as a function of age in T
cells ex vivo and in vitro. With increasing age, shortening of the terminal
ends of chromosomes (telomeres) in T cells has been found. Reactive oxygen
species, produced during a normal immune response, are likely to be major
contributors to the background levels of DNA damage in T cells. Indeed, oxi
dative DNA damage has been shown to accumulate in human T cell clones in vi
tro grown under standard culture conditions. Work on fibroblasts has demons
trated that telomeres are particularly susceptible to oxidative damage, whi
ch they are unable to repair. The importance of oxidative stress in the ind
uction of human cell DNA damage and alteration of proliferative potential i
s supported by the findings that fibroblast strains with a very good antiox
idant capacity have a reduced rate of telomere shortening and extended life
span in vitro, when compared to fibroblast strains with lower antioxidant c
apacity. An age-related accumulation of DNA damage and telomere shortening
in T cells may lead to cell death and/or cell cycle arrest/delay, the outco
me of which may be the generation of fewer T cells following an antigenic s
timulus, so resulting in a less effective immune response. Interventions ai
med at slowing down the accumulation of such DNA damage and/or telomere sho
rtening may have a major impact on the maintenance of an efficient immune r
esponse with increasing age.