Factor-Litvak Pam, Susser Ezra, Kezios Katrina, McKeague Ian, Kark Jeremy D, Hoffman Matthew, Kimura Masayuki, Wapner Ronald, Aviv Abraham
Departments of Epidemiology, and.
Departments of Epidemiology, and New York State Psychiatric Institute, New York, New York;
Pediatrics. 2016 Apr;137(4). doi: 10.1542/peds.2015-3927. Epub 2016 Mar 11.
In adults, leukocyte telomere length (LTL) is variable, familial, and longer in women and in offspring conceived by older fathers. Although short LTL is associated with atherosclerotic cardiovascular disease, long LTL is associated with major cancers. The prevailing notion is that LTL is a "telomeric clock," whose movement (expressed in LTL attrition) reflects the pace of aging. Accordingly, individuals with short LTL are considered to be biologically older than their peers. Recent studies suggest that LTL is largely determined before adulthood. We examined whether factors that largely characterize LTL in adults also influence LTL in newborns.
LTL was measured in blood samples from 490 newborns and their parents.
LTL (mean ± SD) was longer (9.50 ± 0.70 kb) in newborns than in their mothers (7.92 ± 0.67 kb) and fathers (7.70 ± 0.71 kb) (both P < .0001); there was no difference in the variance of LTL among the 3 groups. Newborn LTL correlated more strongly with age-adjusted LTL in mothers (r = 0.47; P < .01) than in fathers (r = 0.36; P < .01) (P for interaction = .02). Newborn LTL was longer by 0.144 kb in girls than in boys (P = .02), and LTL was longer by 0.175 kb in mothers than in fathers (P < .0001). For each 1-year increase in father's age, newborn LTL increased by 0.016 kb (95% confidence interval: 0.04 to 0.28) (P = .0086).
The large LTL variation across newborns challenges the telomeric clock model. Having inherently short or long LTL may be largely determined at birth, anteceding by decades disease manifestation in adults.
在成年人中，白细胞端粒长度（LTL）存在个体差异，具有家族性，且在女性以及由年长父亲所孕育的后代中更长。尽管短LTL与动脉粥样硬化性心血管疾病相关，但长LTL与主要癌症相关。普遍的观点认为LTL是一个“端粒时钟”，其移动（以LTL损耗表示）反映衰老的速度。因此，LTL短的个体被认为在生物学上比同龄人更老。最近的研究表明，LTL在很大程度上是在成年前就已确定。我们研究了在成年人中很大程度上表征LTL的因素是否也会影响新生儿的LTL。
对490名新生儿及其父母的血样进行LTL测量。
新生儿的LTL（平均值±标准差）（9.50±0.70 kb）比其母亲（7.92±0.67 kb）和父亲（7.70±0.71 kb）更长（P均＜0.0001）；三组之间LTL的方差无差异。新生儿LTL与母亲经年龄调整后的LTL的相关性（r = 0.47；P＜0.01）比与父亲的相关性（r = 0.36；P＜0.01）更强（交互作用P = 0.02）。女孩的新生儿LTL比男孩长0.144 kb（P = 0.02），母亲的LTL比父亲长0.175 kb（P＜0.0001）。父亲年龄每增加1岁，新生儿LTL增加0.016 kb（95%置信区间：0.04至0.28）（P = 0.0086）。
新生儿中LTL的巨大差异对端粒时钟模型提出了挑战。出生时LTL固有地短或长可能在很大程度上已确定，早于成年人疾病表现数十年。
