关键词: Aging All-cause mortality Cardiovascular mortality Immune cell phenotype Immune system Immunosenescence Inflammaging Non-cardiovascular mortality T cells

来  源:   DOI:10.1186/s12979-024-00431-6   PDF(Pubmed)

Abstract:
BACKGROUND: Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001).
RESULTS: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03-1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13-1.49], 1.5 [1.12-1.99], respectively).
CONCLUSIONS: In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.
摘要:
背景:全球预期寿命正在上升,到2050年,60岁以上的年龄组预计将达到20亿。衰老会影响免疫系统。免疫系统衰老的一个值得注意的标记是衰老相关免疫细胞表型(ARIP)的存在。尽管它们很重要,包括ARIPs在内的免疫细胞表型与死亡率之间的联系未得到充分研究.我们使用流式细胞术和IL-6前瞻性研究了参加第七次检查(1998-2001)的无痴呆弗雷明汉心脏研究(FHS)后代队列参与者中16种不同的免疫细胞表型与生存结果的关系。
结果:在996名参与者中(平均年龄62岁,40到88年,52%女性),19年生存率为65%.调整年龄,性别,和巨细胞病毒(CMV)血清状态,较高的CD4/CD8和Tc17/CD8+Treg比率与较低的全因死亡率显著相关(HR:0.86[0.76-0.96],0.84[0.74-0.94],分别),而较高的CD8调节细胞水平(CD8+CD25+FoxP3+)与全因死亡风险增加相关(HR=1.17,[1.03-1.32]).IL-6水平升高与全因升高相关,心血管,和非心血管死亡率(HR=1.43[1.26-1.62],1.70[1.31-2.21],和1.36[1.18-1.57],分别)。然而,在调整了心血管危险因素和流行的癌症后,性别,和CMV,在我们的队列中,免疫细胞表型与死亡率不再相关.尽管如此,IL-6仍然与全因死亡率和心血管死亡率显著相关(HR:1.3[1.13-1.49],1.5[1.12-1.99],分别)。
结论:在19年的随访中,较高的Tc17/CD8+Treg和CD4/CD8比值与较低的全因死亡率相关,而CD8+CD25+FoxP3+(CD8+Treg)表型显示风险增加。IL-6水平升高与死亡风险增加一致相关。这些发现强调了免疫表型和死亡率之间的联系,建议对未来研究和临床考虑的影响。
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