Born to be young: prenatal thyroid hormones increase early-life telomere length

Abstract

43 44 Character count: 9400 45 Reference count: 15 46 47 Keywords 48 Aging, mitochondria, telomere length, bird, fetal programming. Abstract 51 Prenatal environmental conditions can have lifelong consequences on health and aging. The 52 underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important 53 regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we 54 manipulated embryo exposure to maternal THs through egg injection and investigated the 55 consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy 56 number and telomere length significantly decrease from early-life to late adulthood, thus confirming 57 that these two molecular markers are hallmarks of aging in our wild bird model. The experimental 58 elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal 59THs had no effect on mtDNA copy number but significantly increased telomere length both soon after 60 birth and at the end of the growth period (equivalent to offsetting ca. 4 years of post-growth telomere 61 shortening). These findings suggest that prenatal THs have a key role in setting the 'biological' age at 62 birth, and thus might influence longevity. 109 enzyme telomerase, responsible for elongating telomeres) contains a binding site for THs (12).110 Consequently, one hypothesis would be that prenatal THs could elongate telomeres early in life 111 through the activation of the telomerase enzyme. The positive correlation found between the mRNA 112 expression of the thyroid-stimulating hormone and telomere length in human adipose tissue could 113 support such an hypothesis (13). 114While the exact mechanisms remain to be identified, our study demonstrates that prenatal TH 115 levels have the potential to elongate telomeres in early-life, and thus to set the 'biological' age at birth. 116This is the first study to show that telomere length at birth could be increased by modulating the 117 prenatal hormonal environment. Thyroid function is known to influence cardiovascular disease risk 118 and life expectancy in adult humans (3), but no information is currently available regarding the impact 119 of prenatal TH exposure on adult health and lifespan. Epidemiological and long-term experimental 120 studies investigating the impact of prenatal THs on lifespan are now required to establish if the effect 121 observed here on telomeres translates into a longevity gain. 122 123 Experimental procedures 124The study was conducted in the long-term monitored population of collared flycatchers on Gotland, 125Sweden (Jordbruksverkets permit no. ID 872). We selected 44 adult birds of known-age (1 to 7 years 126 old, i.e. cross-sectional data; maximum lifespan = 9.8 years) from the long-term monitoring program. 127Thirty-two nests were used for the prenatal manipulation of THs, 16 Control (vehicle-injected) and 16 128 TH nests in which eggs were injected with ca. a 2SD increase of TH egg content based on natural ...

Testing the short-and long-term effects of elevated prenatal exposure to different forms of thyroid hormones

“…In turn, the lack of treatment effects on adult oxidative status may suggest no organisational effects of prenatal THs on adult metabolism. Two recent studies in altricial species also found no influence of yolk THs on nestling oxidative stress ( Hsu et al, 2019 ; Sarraude et al, 2020 ), yet telomere length, a biomarker of aging was affected ( Stier et al, 2020 ). Our study shows for the first time that prenatal THs have no influence on adult oxidative stress either.…”