Open Access Highly Accessed Open Badges Research

Slower immune system aging in women versus men in the Japanese population

Katsuiku Hirokawa123*, Masanori Utsuyama12, Yoshio Hayashi1, Masanobu Kitagawa2, Takashi Makinodan4 and Tamas Fulop5

Author Affiliations

1 Institute for Health and Life Sciences, Tokyo Medical & Dental University Open Laboratory, Medical Research Institute Surugadai Bldg, 2-3-10, Surugadai, Kanda, Chiyoda-ku, Tokyo 101-0062, Japan

2 Department of Comprehensive Pathology, Tokyo Medical & Dental University, Tokto, Japan

3 Nakanosogo Hospital, Tokto, Japan

4 UCLA, Los Angeles, USA

5 Research Center on Aging, University of Sherbrooke, Sherbrooke, Canada

For all author emails, please log on.

Immunity & Ageing 2013, 10:19  doi:10.1186/1742-4933-10-19

Published: 15 May 2013



Gender-related differences in humans are commonly observed in behaviour, physical activity, disease, and lifespan. However, the notion that age-related changes in the immune system differ between men and women remains controversial. To elucidate the relationship between immunological changes and lifespan, peripheral blood mononuclear cells from healthy Japanese subjects (age range: 20–90 years; N = 356) were analysed by using three-colour flow cytometry. The proliferative activities and cytokine-producing capacities of T cells in response to anti-CD3 monoclonal antibody stimulation were also assessed.


An age-related decline in the number of T cells, certain subpopulations of T cells (including CD8+ T cells, CD4+CDRA+ T cells, and CD8+CD28+ T cells), and B cells, and in the proliferative capacity of T cells was noted. The rate of decline in these immunological parameters, except for the number of CD8+ T cells, was greater in men than in women (p < 0.05). We observed an age-related increase or increasing trend in the number of CD4+ T cells, CD4+CDRO+ T cells, and natural killer (CD56+CD16+) cells, as well as in the CD4+ T cell/CD8+ T cell ratio. The rate of increase of these immunological parameters was greater in women than in men (p < 0.05). T cell proliferation index (TCPI) was calculated from the T cell proliferative activity and the number of T cells; it showed an age-related decline that was greater in men than in women (p < 0.05). T cell immune score, which was calculated using 5 T cell parameters, also showed an age-related decline that was greater in men than in women (p < 0.05). Moreover, a trend of age-related decreases was observed in IFNγ, IL-2, IL-6, and IL-10 production, when lymphocytes were cultured with anti-CD3 monoclonal antibody stimulation. The rate of decline in IL-6 and IL-10 production was greater in men than in women (p < 0.05).


Age-related changes in various immunological parameters differ between men and women. Our findings indicate that the slower rate of decline in these immunological parameters in women than that in men is consistent with the fact that women live longer than do men.

Ageing; Immune system; Gender difference; T cells; T cell immune score; T cell proliferation index; CD8+CD28+ T cells