Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Moreno-Navarrete, José María; Liñares-Pose, Laura; Sabater, Mònica; Rial-Pensado, Eva; Comas, Ferran; Jové, Mariona; Latorre, Jèssica; Ortega, Francisco; Ricart, Wifredo; Portero‐Otín, Manuel; López, Miguel; Fernández‐Real, José Manuel

doi:10.1159/000495170

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…Consequently, one hypothesis would be that prenatal THs could elongate telomeres early in life through the activation of the telomerase enzyme. The positive correlation found between the mRNA expression of the thyroid-stimulating hormone and telomere length in human adipose tissue could support such an hypothesis (13).…”

Section: Main Textmentioning

confidence: 81%

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

Stier

Hsu

Marciau

et al. 2020

Preprint

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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 ...

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Section: Main Textmentioning

confidence: 81%

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

Stier

Hsu

Marciau

et al. 2020

Preprint

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“…It has been observed in animal and cell models that the activation of TSH receptors was related to the lipolysis of white adipose tissue and the accumulation of TG. Therefore, the activation of TSH receptors in adipose tissue may affect the distribution of body fat 27,28 . In addition, some studies reported that the relationship between TSH and systemic fat and obesity was likely mediated by leptin, which is a protein produced almost exclusively by fat cells that has been found to modulate the gene expression of thyrotropin‐releasing hormone in the paraventricular nucleus and thus increase the TSH releasing 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Correlations between neck circumference and serum thyroid hormones levels in postmenopausal women with euthyroid and subclinical hypothyroidism

Jian

et al. 2020

Clin Exp Pharma Physio

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Middle‐aged and elderly women are at a higher risk of subclinical hypothyroidism (SHypo). Menopause is an important period of metabolic change in women and thyroid hormones are closely related to metabolic status. Neck circumference (NC) is a simple anthropometric index that reflects upper body fat accumulation. Therefore, this study aimed to explore the relationship between NC and thyroid hormones in postmenopausal women. A total of 1050 postmenopausal women were enrolled from Shanghai Zhabei communities (888 euthyroid subjects and 162 SHypo patients). Anthropometric parameters, including NC, were measured. The measurements of serum thyroid hormones were performed by electrochemical luminescence immunoassay. The results showed NC was positively correlated with thyroid‐stimulating hormone (TSH) (r = .064, P = .039). TSH and the proportion of SHypo patients increased significantly in those with elevated NC (both P < .05). In logistic regression analysis, the risk of SHypo increased by 46.4% in those with elevated NC (OR = 1.464 [1.035–2.071], P = .031). After adjusting for metabolic confounding factors, the positive association disappeared (P = .112). Multiple linear regression analysis showed there were no significant correlations between NC and TSH in either univariate or multivariate model in the total population (both P > .05). And in the subgroup analysis of euthyroid and SHypo individuals, NC was also not related to TSH (all P > .05). In conclusion, there was no independent association between NC, a simple anthropometric index for upper body fat accumulation, and serum TSH levels in Chinese euthyroid and SHypo postmenopausal women.

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“…Lipidomics technologies can be used to measure hundreds of lipids in human biofluid or tissue [12,24]. However, few lipidomic analysis have been performed on human adipose tissue [25,26,27]. Lipidomics is a platform-dependent technique and numerous sample preparation methods have been reported [28,29,30,31,32].…”

Section: Introductionmentioning

confidence: 99%

Lipidomics of human adipose tissue reveals diversity between body areas

et al. 2020

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Background and aims Adipose tissue plays a pivotal role in storing excess fat and its composition reflects the history of person's lifestyle and metabolic health. Broad profiling of lipids with mass spectrometry has potential for uncovering new knowledge on the pathology of obesity, metabolic syndrome, diabetes and other related conditions. Here, we developed a lipidomic method for analyzing human subcutaneous adipose biopsies. We applied the method to four body areas to understand the differences in lipid composition between these areas. Materials and methods Adipose tissue biopsies from 10 participants were analyzed using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The sample preparation optimization included the optimization of the lipid extraction, the sample amount and the sample dilution factor to detect lipids in an appropriate concentration range. Lipidomic analyses were performed for adipose tissue collected from the abdomen, breast, thigh and lower back. Differences in lipid levels between tissues were visualized with heatmaps. Results Lipidomic analysis on human adipose biopsies lead to the identification of 186lipids in 2 mg of sample. Technical variation of the lipid-class specific internal standards were below 5%, thus indicating acceptable repeatability. Triacylglycerols were highly represented in the adipose tissue samples, and lipids from 13 lipid classes were identified. Long polyunsaturated triacylglycerols in higher levels in thigh (q<0.05), when compared with the abdomen, breast and lower back, indicating that the lipidome was area-specific.

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Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Cited by 5 publications

References 54 publications

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

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

Correlations between neck circumference and serum thyroid hormones levels in postmenopausal women with euthyroid and subclinical hypothyroidism

Lipidomics of human adipose tissue reveals diversity between body areas

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