Determinants and modifiable factors of telomere length in children and adolescents

Abstract

Telomeres are special functional complexes located at the ends of chromosomes with key functions in protecting the DNA integrity. Telomere length (TL) has been suggested as a biomarker indicative of cellular and biological health and potentially reflecting the risk of subsequent disease development. While TL has been increasingly used as a biomarker to reflect health condition in childhood and different stages of human life, evidence on factors determining TL in childhood and adolescence is still limited. To address this important knowledge gap, a series of original studies were conducted and included in this thesis to examine the determinants and potentially modifiable factors of TL at different levels. The first study was a meta-analysis to test for any negative association between smoking behaviours and TL. The second study was a longitudinal study on 753 mother-infant dyads to study the impact of adverse intrauterine environment on neonatal TL. The third study examines the impact of childhood-onset allergic diseases on TL in early adolescence. The fourth study explored the associations between serum pro-inflammatory cytokines levels and TL in adolescents with different characteristics. The fifth study was a 5-year longitudinal study on a cohort of 92 children delineating the impact of early-life exposure to family financial pressure on their TL in early adolescence. The meta-analysis in study 1 revealed a significantly negative effect of smoking behaviours on TL (Hedge’s g = -0.33, p < 0.001). The subgroup analyses further showed that participants’ characteristics (age and ethnicity) as well as methodological factors (study design, source of tissues, and telomere measurement techniques) could significantly affect the association. Study 2 on mother-infant dyads provided more evidence on the negative effects of adverse intrauterine environment on TL. In this study, neonates born to mothers with infection during pregnancy were found to have shorter cord blood TL (β = -0.17, p = 0.030). Study 3 observed significant interactions between recent snoring status and childhood-onset allergic disease on TL in early adolescence (β = -0.34, p = 0.002), which highlights the importance of proper management of allergic diseases. Study 4 identified the significant role of macrophages in the process of cellular aging, especially among overweight and obese adolescents, by showing the significant associations between TL and peripheral monokines (β = -0.24 to - 0.30, all p < 0.05). Findings in study 5 revealed a spill-over effect of parental financial perceptions and related emotions into children’s health as indicated by the telomere shortening among children from family with high financial pressure (β = -0.61, p = 0.042). This thesis broadened our understanding towards the determinants and potentially modifiable factors of TL of children and adolescents at different levels including risk behaviours, maternal influences, physical health, unhealthy lifestyle, as well as family environment. Study findings of this thesis shed light on the potential application of TL as a biomarker in reflecting child health in relation to early adverse experiences. These will guide future studies to affirm whether TL differences related to early adverse environment is predictive of later life morbidities.