Newborn telomere length predicts later life telomere length: Tracking telomere length from birth to child- and adulthood

Abstract

Background: Telomere length (TL) is considered a biological marker of aging and may indicate age-related disease susceptibility. Adults and children show a fixed ranking and tracking of TL over time. However, the contribution of an individual's initial birth TL to their later life TL is unknown. We evaluated change and tracking of TL from birth to child- and adulthood.

Methods: Telomere length at birth was measured using qPCR in two independent prospective birth cohorts. After a median follow-up period of 4 years in ENVIRONAGE (n = 273) we assessed leukocyte telomere length (LTL) and after 23 years in EFPTS (n = 164) buccal TL was assessed. Correlations and multivariable regression models were applied to study telomere tracking and determinants of TL change from birth onwards.

Findings: In children, LTL at the age of 4 correlates with TL at the start of life both in cord blood (r = 0.71, P < 0.0001;) and placenta (r = 0.60, P < 0.0001) and was -11.2% and -33.1% shorter, respectively. In adulthood, buccal TL at the age of 23 correlates with placental TL (r = 0.46, P < 0.0001) and was -35.9% shorter. TL attrition was higher in individuals with longer birth TL. However, based on TL ranking, individuals do not tend to change dramatically from TL rank after 4 or 23 years of follow-up. Finally, longer maternal TL associates with lower telomere attrition in the next generation.

Interpretation: The high prediction of newborn TL for later life TL, and stable TL ranking from birth onwards underscores the importance of understanding the initial setting of newborn TL and its significance for later life.

Funding: European Research Council (ERC-StG310898) and Flemish Scientific Fund (12X9620N).

Keywords: Early life aging; Newborn telomere length; Telomere dynamics; Telomere tracking.

Fig. 1

Flowchart for selecting participants in ENVIRONAGE (a) and EFPTS (b). For ENVIRONAGE 912 mother-child pairs were eligible for a follow-up study. In total 439 mother-child pairs participated due to a loss of contact from 145 (15.6%), 321 refused participation (35.2%) and 7 (0.8%) could not participate due to language difficulties. A total of 293 (66.7%) mothers and children provided consent for blood drawn, resulting in 273 children with baseline TL (cord blood) and follow-up LTL. The EFPTS study comprised 242 twins with both a placental and buccal swab sample from the Loos et al., 2001 study , of which 164 twins had a proper TL determined in both placenta and buccal swab.

Fig. 2

Telomere tracking from birth to child- and adulthood. a) Pearson correlation between cord blood TL at birth and LTL at the age of 4. b) Pearson correlation between placental TL at birth and LTL at the age of 4. c) Spearman correlation between placental TL at birth and buccal TL at the age of 23. Telomere lengths are normalized and measured for ENVIRONAGE (panel a and b) and EFPTS (panel c) participants separately.

Fig. 3

Change of newborn TL over time. a) Change of cord blood TL at birth compared with LTL at the age of 4-years. b) Change of placental TL at birth compared with LTL at the age of 4 years. c) Change of placental TL at birth compared with buccal TL at the age of 23 years.

Fig. 4

Change of TL ranking over child-and adulthood, using quintiles of the TL distribution at birth and follow-up. ∆Quintiles=difference in quintile at birth and follow-up (Q_follow-up – Q_birth). a) Change in cord blood TL rank of the first 4 years of life. b) Change of placental TL rank of the first 4 years of life. c) Change of placental TL rank of the first 23 years of life.