scholarly journals Born to be young? Prenatal thyroid hormones increase early-life telomere length in wild collared flycatchers

2020 ◽  
Vol 16 (11) ◽  
pp. 20200364
Author(s):  
Antoine Stier ◽  
Bin-Yan Hsu ◽  
Coline Marciau ◽  
Blandine Doligez ◽  
Lars Gustafsson ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Copy Number ◽  
Growth Period ◽  
Mtdna Copy Number ◽  
Cross Sectional ◽  
Telomere Shortening ◽  
Underlying Mechanisms ◽  
Age At Birth

The underlying mechanisms of the lifelong consequences of prenatal environmental condition on health and ageing remain little understood. Thyroid hormones (THs) are important regulators of embryogenesis, transferred from the mother to the embryo. Since prenatal THs can accelerate early-life development, we hypothesized that this might occur at the expense of resource allocation in somatic maintenance processes, leading to premature ageing. Therefore, we investigated the consequences of prenatal TH supplementation on potential hallmarks of ageing in a free-living avian model in which we previously demonstrated that experimentally elevated prenatal TH exposure accelerates early-life growth. Using cross-sectional sampling, we first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus suggesting that these two molecular markers could be hallmarks of ageing in our wild bird model. Elevated prenatal THs had no effect on mtDNA copy number but counterintuitively increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca 4 years of post-growth telomere shortening). These findings suggest that prenatal THs might have a role in setting the ‘biological' age at birth, but raise questions about the nature of the evolutionary costs of prenatal exposure to high TH levels.

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

2020 ◽  
Author(s):  
Antoine Stier ◽  
Bin-Yan Hsu ◽  
Coline Marciau ◽  
Blandine Doligez ◽  
Lars Gustafsson ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Copy Number ◽  
Growth Period ◽  
Postnatal Growth ◽  
Mtdna Copy Number ◽  
Underlying Mechanisms ◽  
Growth And Aging ◽  
Positive Effect

AbstractPrenatal environmental conditions can have lifelong consequences on health and aging. The underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we manipulated embryo exposure to maternal THs through egg injection and investigated the consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus confirming that these two molecular markers are hallmarks of aging in our wild bird model. The experimental elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal THs had no effect on mtDNA copy number but significantly increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca. 4 years of post-growth telomere shortening). These findings suggest that prenatal THs have a key role in setting the ‘biological’ age at birth, and thus might influence longevity.

scholarly journals Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits

2021 ◽  
Author(s):  
Bin-Yan Hsu ◽  
Nina Cossin-Sevrin ◽  
Antoine Stier ◽  
Suvi Ruuskanen
Keyword(s):  
Oxidative Stress ◽  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Later Life ◽  
Delayed Effect ◽  
Oxidative Stress Biomarkers ◽  
Term Survival ◽  
Telomere Shortening ◽  
The Impact

Early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, its underlying proximate mechanisms and consequences on survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.

scholarly journals Football and Team Handball Training Postpone Cellular Aging in Women

2021 ◽  
Author(s):  
Marie Hagman ◽  
Bjørn Fristrup ◽  
Rémi Michelin ◽  
Peter Krustrup ◽  
Muhammad Asghar
Keyword(s):  
Telomere Length ◽  
Mitochondrial Function ◽  
Copy Number ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cellular Aging ◽  
Elderly Subjects ◽  
Mtdna Copy Number ◽  
Cross Sectional ◽  
Team Handball

Abstract Aims: Several hallmarks of aging have been identified and examined separately in previous exercise studies. For the first time, this study investigates the effect of lifelong regular exercise in humans on two of the central aging hallmarks combined. Methods: This cross-sectional study involved 129 healthy, non-smoking women, including young elite football players (YF, n=29), young untrained controls (YC, n=30), elderly team handball players (EH, n=35) and elderly untrained controls (EC, n=35). From a resting blood sample, mononuclear cells (MNCs) were isolated and sorted into monocytes and lymphocytes. Telomere length, mitochondrial (mtDNA) copy number and mitochondrial function (PGC-1α and PGC-1β expression) were measured using quantitative polymerase chain reaction (qPCR). Results: Overall, young women showed significantly longer telomeres and higher mitochondrial function, but lower mtDNA copy number compared to elderly subjects. A multivariate analysis showed that YF had 22–24% longer telomeres in lymphocytes and MNCs compared to YC. In addition, YF showed 19–20% higher mtDNA copy number in lymphocytes and MNCs compared to YC. The two young groups did not differ in PGC-1α and PGC-1β expression. EH showed 14% lower mtDNA copy number in lymphocytes compared to EC, but 3.4-fold higher lymphocyte PGC-1α expression compared to EC. In MNCs, EH also showed 1.4-1.6- fold higher mitochondrial function. The two elderly groups did not differ in telomere length.Conclusion: Elite football training and lifelong team handball training are associated with anti-aging mechanisms in leukocytes in women, including maintenance of telomere length and upregulation of mitochondrial function.

scholarly journals OR03-04 The Study of Cell Senescence in Cortisol-Producing Adrenocortical Adenomas

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Xin Gao ◽  
Yuto Yamazaki ◽  
Jacopo Pieroni ◽  
Yuta Tezuka ◽  
Kei Omata ◽  
...  
Keyword(s):  
Telomere Length ◽  
Tumor Cells ◽  
Copy Number ◽  
Cell Senescence ◽  
Endocrine Disorders ◽  
Mtdna Copy Number ◽  
Telomere Shortening ◽  
Clear Cells ◽  
Adrenocortical Adenomas ◽  
Mtdna Deletion

Abstract Introduction Aging is associated with the pathogenesis of many endocrine disorders such as cardiovascular diseases and diabetes. Cell senescence has been reported as one of their mechanisms. In addition, stress responsiveness has been reported to be associated with cell senescence. In addition, some genetic abnormalities such as mitochondrial DNA (mtDNA) damages or telomere shortening, have been detected in some endocrine disorders. Cortisol is a well-known stress-induced hormone and closely associated with aging. We previously reported that cortisol-producing adenoma (CPA) more abundantly expressed cell senescent markers such as p16 and p21 than other hormone-producing adrenocortical adenomas. However, the detailed pathophysiology of cell senescence and its association with histological features in CPAs have remained virtually unknown. Therefore, we analyzed cell senescent markers (telomere length, mtDNA copy number, mtDNA deletion and p16 and p21 immunoreactivity) and analyzed their correlation with clinicopathological factors in CPA patients. Methods & Materials Forty CPA cases was immunohistochemically evaluated. Twenty CPA, ten adjacent ZF and six non-functional adenoma (NFA) were examined for mtDNA abnormalities. mtDNA deletion was evaluated by nested-PCR and mtDNA copy number and telomere length were measured using real-time PCR. Results p21 immunoreactivity was significantly higher in CPA than that of adjacent ZF (P=0.0001) and significantly inversely correlated with tumor size (P=0.0004). Telomere length was much longer in CPA than that in adjacent ZF(P=0.0038), and NFA (P=0.0018). mtDNA copy number of NFA was significantly higher than that of CPA and adjacent ZF (P=0.0038). mtDNA copy number of compact cells was significantly higher than that of clear cells (P=0.0432). mtDNA copy number of compact cells was positively correlated with urinary free cortisol (UFC) (P=0.0428) and plasma cortisol (F) (P=0.0609). mtDNA copy number of clear cells were inversely correlated with F (0.0497). 4977 bp mtDNA deletion was more frequently detected in CPA (54%) and in adjacent ZF (50%) than in NFA (17%). Discussion Results of our present study did reveal that CPA harbored more senescent phenotype as demonstrated by abundant p16 and p21, marked telomere shortening, frequent mtDNA 4977bp deletion and relatively low mtDNA copy number, possibly caused by long-term exposure of excessive cortisol in situ compared to NFA. In addition, clear tumor cells could represent more senescent histological phenotype because of their lower mtDNA copy numbers. This is the first study to demonstrate that compact tumor cells were biologically more active than clear tumor cells and could reflect clinical cortisol biosynthesis, resulting in marked functional intratumoral heterogeneity in CPAs.

scholarly journals Football and team handball training postpone cellular aging in women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie Hagman ◽  
Bjørn Fristrup ◽  
Rémi Michelin ◽  
Peter Krustrup ◽  
Muhammad Asghar
Keyword(s):  
Telomere Length ◽  
Copy Number ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cross Sectional Study ◽  
Cellular Aging ◽  
Elderly Subjects ◽  
Mtdna Copy Number ◽  
Cross Sectional ◽  
Team Handball

AbstractSeveral hallmarks of aging have been identified and examined separately in previous exercise studies. For the first time, this study investigates the effect of lifelong regular exercise in humans on two of the central aging hallmarks combined. This cross-sectional study involved 129 healthy, non-smoking women, including young elite football players (YF, n = 29), young untrained controls (YC, n = 30), elderly team handball players (EH, n = 35) and elderly untrained controls (EC, n = 35). From a resting blood sample, mononuclear cells (MNCs) were isolated and sorted into monocytes and lymphocytes. Telomere length, mitochondrial (mtDNA) copy number and key regulators of mitochondrial biogenesis and function (PGC-1α and PGC-1β expression) were measured using quantitative polymerase chain reaction (qPCR). Overall, young women showed significantly longer telomeres and higher PGC-1α and PGC-1β expression, but lower mtDNA copy number compared to elderly subjects. A multivariate analysis showed that YF had 22–24% longer telomeres in lymphocytes and MNCs compared to YC. In addition, YF showed 19–20% higher mtDNA copy number in lymphocytes and MNCs compared to YC. The two young groups did not differ in PGC-1α and PGC-1β expression. EH showed 14% lower mtDNA copy number in lymphocytes compared to EC, but 3.4-fold higher lymphocyte PGC-1α expression compared to EC. In MNCs, EH also showed 1.4–1.6-fold higher PGC-1α and PGC-1β expression. The two elderly groups did not differ in telomere length. Elite football training and lifelong team handball training are associated with anti-aging mechanisms in leukocytes in women, including maintenance of telomere length and superior mitochondrial characteristics.

scholarly journals mtDNA in the Pathogenesis of Cardiovascular Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Lili Wang ◽  
Qianhui Zhang ◽  
Kexin Yuan ◽  
Jing Yuan
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Heart Diseases ◽  
Mtdna Copy Number ◽  
Cardiac Inflammation ◽  
Ischemic Heart Diseases ◽  
Metabolic Functions ◽  
Underlying Mechanisms

The incidence rate of cardiovascular disease (CVD) has been increasing year by year and has become the main cause for the increase of mortality. Mitochondrial DNA (mtDNA) plays a crucial role in the pathogenesis of CVD, especially in heart failure and ischemic heart diseases. With the deepening of research, more and more evidence showed that mtDNA is related to the occurrence and development of CVD. Current studies mainly focus on how mtDNA copy number, an indirect biomarker of mitochondrial function, contributes to CVD and its underlying mechanisms including mtDNA autophagy, the effect of mtDNA on cardiac inflammation, and related metabolic functions. However, no relevant studies have been conducted yet. In this paper, we combed the current research status of the mechanism related to the influence of mtDNA on the occurrence, development, and prognosis of CVD, so as to find whether these mechanisms have something in common, or is there a correlation between each mechanism for the development of CVD?

scholarly journals 3106 The influence of early life experience on telomere length, health, and behavior of domestic cats

2019 ◽  
Vol 3 (s1) ◽  
pp. 23-23
Author(s):  
Mikel Maria Delgado ◽  
Melissa Bain ◽  
Tony C.A.T. Buffington
Keyword(s):  
Telomere Length ◽  
Reference Gene ◽  
Early Life ◽  
Maternal Separation ◽  
Single Copy ◽  
Physical Contact ◽  
Telomere Shortening ◽  
Blood Samples ◽  
Future Studies ◽  
And Behavior

OBJECTIVES/SPECIFIC AIMS: The primary objective of this research is to determine whether being hand-reared, and deprived of early maternal interaction, will affect telomere length in orphaned kittens. The secondary goal is to examine how early maternal separation impacts the health, growth and behavior of orphaned kittens. METHODS/STUDY POPULATION: Kittens were fostered through local rescue groups and shelters. We collected blood samples from 42 orphaned kittens during the first week of their lives. Due to high mortality of this population, we obtained a second blood sample at eight weeks of age from only 30 of these kittens. We collected blood samples from 12 control kittens raised with mothers at during the first and eighth weeks of life. Blood samples are currently being processed with real time quantitative PCR (qPCR) by the Real-time PCR Research and Diagnostics Core Facility at the UC Davis School of Veterinary Medicine (SVM). This includes RNA extraction, cDNA synthesis, Reference Gene Validation, and qPCR analysis. Relative telomere length (RTL) will be calculated by comparing the average telomere abundance across three samples cells with that of a reference gene (single copy number) for each sample. The resulting T/S ratio (telomere to single copy) is proportional to the average telomere length. If T/S = 1, then telomere length in the sample and the reference are the same. RESULTS/ANTICIPATED RESULTS: Because telomeres show the fastest rate of shortening early in life, we predict that maternal separation will increase the rate of telomere shortening in kittens. We also predict that the telomeres of orphaned kittens will be shorter at both one week and eight weeks of age, compared to controls. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will increase our understanding of early life adversity, a finding that can translate to other mammals. It will inform the practice of fostering neonatal kittens, and illuminate whether these kittens might be at higher risk than mother-reared kittens for health problems (which could be investigated in future studies). If significant telomere shortening occurs between collection periods, then future studies can take more frequent blood samples to determine what stages of early development are potentially most sensitive. If differences between groups are found, this will establish a protocol for several future research projects, such as testing whether these detrimental effects can be mitigated by environmental enrichment via activation of telomerase. Telomerase is an enzyme that appears to counteract some shortening of telomeres, and is activated by several external factors, including exercise. Thus, a logical follow up study would be developing and testing age-specific and appropriate enrichments that may activate telomerase and reduce telomere loss. Physical contact, whether human, mother, or siblings, is another possible source of telomerase activation in young kittens. Future studies also could quantify the effects of different sources of physical contact on telomere shortening. Finally, a positive finding would establish a need for longitudinal studies of the effects of early weaning on feline health and behavior and whether differences in early-life telomere lengths predict health and longevity of cats.

scholarly journals Increased telomere length and mtDNA copy number induced by multi-walled carbon nanotube exposure in the workplace

2020 ◽  
Vol 394 ◽  
pp. 122569
Author(s):  
Manosij Ghosh ◽  
Lisa Janssen ◽  
Dries S. Martens ◽  
Deniz Öner ◽  
Jelle Vlaanderen ◽  
...  
Keyword(s):  
Carbon Nanotube ◽  
Telomere Length ◽  
Copy Number ◽  
Mtdna Copy Number ◽  
Multi Walled Carbon Nanotube

Telomere Length Among the Elderly and Oldest-Old

2005 ◽  
Vol 8 (5) ◽  
pp. 425-432 ◽  
Author(s):  
Claus Bischoff ◽  
Jesper Graakjaer ◽  
Hans Christian Petersen ◽  
Bernard Jeune ◽  
Vilhelm A. Bohr ◽  
...  
Keyword(s):  
Telomere Length ◽  
Oldest Old ◽  
The Elderly ◽  
Specific Difference ◽  
Cross Sectional ◽  
Telomere Shortening ◽  
Telomere Sequence ◽  
Age Dependent ◽  
The Mean ◽  
Telomere Loss

AbstractHuman chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.

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