Telomere length dynamics across the human lifespan: A systematic review and meta-analysis

This systematic review aims to evaluate the dynamics of telomere length (TL), a biomarker used to assess biological aging and disease states, across the human lifespan and the impact of methodological and disease factors. Following a pre-registered protocol, studies on TL published before 2022 were collected from PubMed and Web of Science and screened based on pre-defined criteria. Summary statistics were extracted from all studies. Correlation between TL and age was used as the effect size and corrected for age-range restriction. Random-effects models were used to pool effect sizes. Impact of health status (healthy, cardiovascular disease, cancer, mental health, general population) and methodological factors was examined through meta-regression. 279 cross-sectional studies across 149,527 subjects (age 0-112years) and 50 longitudinal studies across 20,351 subjects (age 0-94years) were included. For cross-sectional studies, the pooled corrected correlation was -0.17 (95%CI: -0.21 to -0.13). The correlation weakened with increasing chronological age (β=0.003, p=.007). Health status did not moderate the correlation. TL measured in saliva (k=14) had a weaker correlation with age than TL measured in blood leukocytes (k=218; β=0.266, p=.004). Magnetic bead DNA extraction method (k=13) moderated the relationship between TL and age compared with salting out (k=57) methods (β=0.412, p<0.001). For longitudinal studies, the yearly z-score change rate of TL ranged from -0.74 to 0.36, with a median change of -0.06. TL decreases with age at a decelerating rate in older ages. Cell type and DNA extraction method may moderate the correlation between TL and age.