Eisenberg Dan T A, Borja Judith B, Hayes M Geoffrey, Kuzawa Christopher W
Department of Anthropology, University of Washington.
Center for Studies in Demography and Ecology, University of Washington.
Am J Hum Biol. 2017 Jul 8;29(4). doi: 10.1002/ajhb.22962. Epub 2017 Jan 25.
Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence.
To test this, BTL measured in young adults (21.7 ± 0.3 years old) from the Philippines (N = 1,759) were linked to prospectively collected early life data on infectious burden.
As predicted, increased early life diarrheal prevalence was associated with shorter adult BTL. The association was most marked for infections experienced from 6 to 12 months, which corresponds with weaning and maximal diarrheal burden. A standard deviation increase in infections at 6-12 m predicts a 45 bp decrease in BTL, equivalent to 3.3 years of adult telomeric aging in this population. Contrary to expectations, breastfeeding duration was not associated with BTL, nor did effects vary by sex.
These findings show that infancy diarrheal disease predicts a marker of cellular aging in adult immune cells. These findings suggest that early life infectious burden may influence late life health, or alternatively, that short TL in early life increases infectious disease susceptibility.
端粒是染色体末端的重复DNA,由于细胞复制和氧化应激,其长度会随着年龄的增长而缩短。随着端粒缩短,这最终可能会限制细胞复制并导致衰老。感染在早期发育过程中很常见,并会激活涉及克隆扩增和氧化应激的细胞免疫反应。因此,高感染疾病负担可能会缩短血液端粒长度(BTL)并加速免疫衰老的进程。
为了验证这一点,对来自菲律宾的年轻成年人(21.7±0.3岁,N = 1759)测量的BTL与前瞻性收集的关于感染负担的早期生活数据进行了关联分析。
正如预期的那样,早年腹泻患病率的增加与成年人较短的BTL相关。这种关联在6至12个月时经历的感染中最为明显,这与断奶和最大腹泻负担相对应。6至12个月时感染增加一个标准差预测BTL会减少45个碱基对,相当于该人群中3.3年的成人端粒衰老。与预期相反,母乳喂养持续时间与BTL无关,且影响也不存在性别差异。
这些发现表明婴儿期腹泻病可预测成人免疫细胞中细胞衰老的一个标志物。这些发现表明早年感染负担可能会影响晚年健康,或者相反,早年较短的端粒长度会增加感染疾病的易感性。