Rais Maham, Wilson Randall M, Urbanski Henryk F, Messaoudi Ilhem
Graduate program in Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
Graduate program in Cell, Molecular, and Developmental Biology, University of California, Riverside, CA, USA.
Geroscience. 2017 Aug;39(4):373-384. doi: 10.1007/s11357-017-9979-5. Epub 2017 Jun 14.
Aging leads to a progressive decline in immune function commonly referred to as immune senescence, which results in increased incidence and severity of infection. In addition, older males experience a significant disruption in their levels of circulating androgens, notably testosterone and dehydroepiandrosterone (DHEA), which has been linked to sarcopenia, osteoporosis, cardiovascular disease, and diabetes. Since sex steroid levels modulate immune function, it is possible that the age-related decline in androgen levels can also affect immune senescence. Therefore, in this study, we evaluated the pleiotropic effects of physiological androgen supplementation in aged male rhesus macaques (n = 7/group) on immune cell subset frequency and response to vaccination. As expected, frequency of naïve CD4 and CD8 T cells declined in aged non-treated macaques, while that of memory T cells increased. In contrast, frequency of naïve and memory T cells remained stable in androgen-supplemented males. In addition, levels of inflammatory cytokines increased less steeply in supplemented aged males compared to the aged controls. Despite these changes, androgen-supplemented animals only showed modest improvement in antibody responses following vaccination compared to age non-treated controls. These data indicate that short-term physiological androgen supplementation can improve some but not all aspects of immune senescence.
衰老会导致免疫功能逐渐衰退，通常称为免疫衰老，这会导致感染的发生率和严重程度增加。此外，老年男性循环雄激素水平，尤其是睾酮和脱氢表雄酮（DHEA）会出现显著紊乱，这与肌肉减少症、骨质疏松症、心血管疾病和糖尿病有关。由于性类固醇水平会调节免疫功能，雄激素水平随年龄下降也可能影响免疫衰老。因此，在本研究中，我们评估了对老年雄性恒河猴（每组n = 7）进行生理剂量雄激素补充对免疫细胞亚群频率和疫苗接种反应的多效性影响。正如预期的那样，未治疗的老年猕猴中初始CD4和CD8 T细胞频率下降，而记忆T细胞频率增加。相比之下，补充雄激素的雄性猕猴中初始和记忆T细胞频率保持稳定。此外，与老年对照组相比，补充雄激素的老年雄性炎症细胞因子水平上升幅度较小。尽管有这些变化，但与未接受治疗的老年对照组相比，补充雄激素的动物在接种疫苗后的抗体反应仅略有改善。这些数据表明，短期生理剂量雄激素补充可以改善免疫衰老的某些方面，但不是全部。
