![]() Newborn TL is the initial setting of TL and highly variable among individuals. Genome-wide association studies (GWAS) have been performed on TL in many adult studies, which have identified TL-linked genetic variants at multiple loci in the human genome: TERC (3q26.2), TERT (5q15.33), RTEL1 (20q13.33), OBFC1 (10q24.3), NAF1 (4q32.2), ZNF208 (19p12), and ACYP2 (2p16.2). In addition to diet, lifestyle, and other environmental exposures, heritable factors such as genetic variants have also been recognized to play a significant role in determining an individual’s TL. Some studies reported diet, parity, and educational attainment to explain inter-individual variation in TL. Multiple studies reported telomere shortening to be associated with hypertension, cardiovascular disease, and mental disorders. Shortened leukocyte TL has been associated with smoking, type 2 diabetes, higher 2-h post-load glucose concentration, lower insulin-like growth factor 1, and higher leptin and homocysteine levels. Sex differences have also been reported in multiple studies with females having longer TL than males. Telomere (TL) is a biomarker of biological aging and has been associated with physiological and environmental stress, age-related diseases, and early mortality. ![]() Telomeres shorten with each cell division, reflecting the age of a cell and the time until senescence. Functionally, telomeres play an important role in maintaining genomic stability and protect chromosomes from end-to-end fusion and degradation. ![]() Telomeres are nucleoprotein structures formed of non-coding tandem repeats of hexamer TTAGGG at the end of the chromosomes. ![]() This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors. Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. Mother’s TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. There were sex-related differences in the factors explaining newborn TL variation. Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP- LRRC34-rs10936600: P meta = 5.95E−08). Longer maternal TL ( β = 0.14, P = 1.99E−05) and higher paternal age ( β = 0.10, P = 3.73E−03) were positively associated with newborn TL. The association between maternal TL and antenatal maternal health was also studied. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. MethodsĪverage relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26–28 weeks of gestation, N = 892) were measured in a birth cohort. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus. Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age.
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