scholarly journals Telomere length determinants in childhood

2020 ◽  
Vol 58 (2) ◽  
pp. 162-177 ◽  
Author(s):  
Vesna Gorenjak ◽  
Alexandros M. Petrelis ◽  
Maria G. Stathopoulou ◽  
Sophie Visvikis-Siest
Keyword(s):  
Telomere Length ◽  
Environmental Conditions ◽  
Early Adulthood ◽  
Child Growth ◽  
Review Article ◽  
Intrauterine Development ◽  
Pathological Conditions ◽  
Telomere Biology ◽  
Cellular Turnover ◽  
Telomere Dynamics

AbstractTelomere length (TL) is a dynamic marker that reflects genetic predispositions together with the environmental conditions of an individual. It is closely related to longevity and a number of pathological conditions. Even though the extent of telomere research in children is limited compared to that of adults, there have been a substantial number of studies providing first insights into child telomere biology and determinants. Recent discoveries revealed evidence that TL is, to a great extent, determined already in childhood and that environmental conditions in adulthood have less impact than first believed. Studies have demonstrated that large inter-individual differences in TL are present among newborns and are determined by diverse factors that influence intrauterine development. The first years of child growth are associated with high cellular turnover, which results in fast shortening of telomeres. The rate of telomere loss becomes stable in early adulthood. In this review article we summarise the existing knowledge on telomere dynamics during the first years of childhood, highlighting the conditions that affect newborn TL. We also warn about the knowledge gaps that should be filled to fully understand the regulation of telomeres, in order to implement them as biomarkers for use in diagnostics or treatment.

scholarly journals Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes

2020 ◽  
Vol 66 (4) ◽  
pp. 35-44
Author(s):  
Ekaterina N. Dudinskaya ◽  
Olga N. Tkacheva ◽  
Natalia V. Brailova ◽  
Irina D. Strazhesko ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Carbohydrate Metabolism ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
The Mean ◽  
Telomere Biology

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

MYOSTATIN - A MODERN UNDERSTANDING OF THE PHYSIOLOGICAL ROLE AND SIGNIFICANCE IN THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES

2021 ◽  
pp. 701-706
Author(s):  
А.А. Газданова ◽  
В.Г. Кукес ◽  
О.К. Парфенова ◽  
Н.Г. Сидоров ◽  
А.В. Перков ◽  
...  
Keyword(s):  
Muscle Growth ◽  
Physiological Role ◽  
Review Article ◽  
Negative Regulator ◽  
Transforming Growth Factors ◽  
Endogenous Factors ◽  
Pathological Conditions ◽  
Physiological Properties ◽  
The Family

Миостатин - белок, принадлежащий к классу миокинов, семейству трансформирующих факторов роста β (TGF-β). В обзорной статье, анализирующей данные литературы, показана ключевая роль миостатина в развитии старческой саркопении и кахексии при различных патологических состояниях, таких как рак, ХСН, ХБП, ХОБЛ и др. В статье рассматривается структура миостатина, подробная схема синтеза и его активации, механизм действия как негативного регулятора роста и дифференцировки мышц при этих патологических состояниях. Выделены основные физиологические свойства и клиническое значение. Рассмотрены экзогенные и эндогенные факторы, регулирующие экспрессию миостатина, и возможные механизмы их действия. Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

scholarly journals Interplays between pre- and post-natal environments affect early-life mortality, body mass and telomere dynamics in the wild

2020 ◽  
Vol 224 (1) ◽  
pp. jeb231290
Author(s):  
Tiia Kärkkäinen ◽  
Pauliina Teerikorpi ◽  
Wiebke Schuett ◽  
Antoine Stier ◽  
Toni Laaksonen
Keyword(s):  
Telomere Length ◽  
Early Life ◽  
Maternal Investment ◽  
Interactive Effects ◽  
Hatching Order ◽  
Hatching Synchrony ◽  
Asynchronous Hatching ◽  
In The Wild ◽  
Developmental Conditions ◽  
Telomere Dynamics

ABSTRACTEarly-life conditions are crucial determinants of phenotype and fitness. The effects of pre- and post-natal conditions on fitness prospects have been widely studied but their interactive effects have received less attention. In birds, asynchronous hatching creates challenging developmental conditions for the last-hatched chicks, but differential allocation in last-laid eggs might help to compensate this initial handicap. The relative importance and potential interaction between pre- and post-hatching developmental conditions for different fitness components remains mostly unknown. We manipulated hatching order in wild pied flycatchers (Ficedula hypoleuca), creating three groups: natural asynchrony (last-laid eggs hatching last), reversed asynchrony (last-laid eggs hatching first) and hatching synchrony (all eggs hatching at once). We examined the effects of these manipulations on early-life survival, growth and telomere length, a potential cellular biomarker of fitness prospects. Mortality was mostly affected by hatching order, with last-hatched chicks being more likely to die. Early-life telomere dynamics and growth were influenced by the interplays between laying and hatching order. Last-laid but first-hatched chicks were heavier but had shorter telomeres 5 days after hatching than their siblings, indicating rapid early growth with potential adverse consequences on telomere length. Synchronous chicks did not suffer any apparent cost of hatching synchronously. Impaired phenotypes only occurred when reversing the natural hatching order (i.e. developmental mismatch), suggesting that maternal investment in last-laid eggs might indeed counterbalance the initial handicap of last-hatched chicks. Our experimental study thus highlights that potential interplays between pre- and post-natal environments are likely to shape fitness prospects in the wild.

scholarly journals Mitochondrial donation in translational medicine; from imagination to reality

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hesam Saghaei Bagheri ◽  
Farhad Bani ◽  
Savas Tasoglu ◽  
Amir Zarebkohan ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Translational Medicine ◽  
Specific Activity ◽  
Current Knowledge ◽  
Review Article ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Pathological Conditions ◽  
Mitochondrial Transfer ◽  
Mitochondrial Donation

Abstract The existence of active crosstalk between cells in a paracrine and juxtacrine manner dictates specific activity under physiological and pathological conditions. Upon juxtacrine interaction between the cells, various types of signaling molecules and organelles are regularly transmitted in response to changes in the microenvironment. To date, it has been well-established that numerous parallel cellular mechanisms participate in the mitochondrial transfer to modulate metabolic needs in the target cells. Since the conception of stem cells activity in the restoration of tissues’ function, it has been elucidated that these cells possess a unique capacity to deliver the mitochondrial package to the juxtaposed cells. The existence of mitochondrial donation potentiates the capacity of modulation in the distinct cells to achieve better therapeutic effects. This review article aims to scrutinize the current knowledge regarding the stem cell’s mitochondrial transfer capacity and their regenerative potential.

scholarly journals Understanding the foot’s functional anatomy in physiological and pathological conditions: the calcaneopedal unit concept

2019 ◽  
Vol 13 (2) ◽  
pp. 134-146 ◽  
Author(s):  
I. Ghanem ◽  
A. Massaad ◽  
A. Assi ◽  
M. Rizkallah ◽  
A. J. Bizdikian ◽  
...  
Keyword(s):  
Functional Anatomy ◽  
Sparse Data ◽  
Standing Position ◽  
Review Article ◽  
Foot Deformities ◽  
Pathological Conditions ◽  
Orthopaedic Literature ◽  
Foot Anatomy

Background A thorough review of the available orthopaedic literature shows significant controversies, inconsistencies and sparse data regarding the terminology used to describe foot deformities. This lack of consensus on terminology creates confusion in professional discussions of foot anatomy, pathoanatomy and treatment of deformities. The controversies apply to joint movements as well as static relationships between the bones. Description The calcaneopedal unit (CPU) is a specific anatomical and physiological entity, represented by the entire foot excepted the talus. The calcaneus, midfoot and forefoot are solidly bound by three strong ligaments that create a unit that articulates with the talus. The movement of the CPU is complex, as it rotates under the talus, around the axis of Henke that coincides with the talo-calcaneal ligament of Farabeuf. This calcaneopedal unit is deformable. It is compared with a twisted plate, able to adapt to many physiological situations in standing position, in order to acheive a plantigrade position. Moreover, the calcaneopedal unit and the talo-tibiofibular complex are interdependent; rotation of the latter produces morphologic modifications inside the former and vice versa. Purpose This paper is a review article of this concept and of its physiopathological applications.

scholarly journals Migration and stress during reproduction govern telomere dynamics in a seabird

2014 ◽  
Vol 10 (1) ◽  
pp. 20130889 ◽  
Author(s):  
Jannik Schultner ◽  
Børge Moe ◽  
Olivier Chastel ◽  
Claus Bech ◽  
Alexander S. Kitaysky
Keyword(s):  
Life History ◽  
Telomere Length ◽  
Physiological State ◽  
Telomere Shortening ◽  
Rissa Tridactyla ◽  
Life History Stages ◽  
Before And After ◽  
Migratory Patterns ◽  
Telomere Dynamics ◽  
Winter Migration

Changes in telomere length are believed to reflect changes in physiological state and life expectancy in animals. However, much remains unknown about the determinants of telomere dynamics in wild populations, and specifically the influence of conditions during highly mobile life-history stages, for example migration. We tested whether telomere dynamics were associated with migratory behaviour and/or with stress during reproduction in free-living seabirds. We induced short-term stress during reproduction in chick-rearing, black-legged kittiwakes ( Rissa tridactyla ), tracked winter migration with geolocators and measured telomere length before and after winter migration. We found that time spent at wintering grounds correlated with reduced telomere loss, while stress during reproduction accelerated telomere shortening. Our results suggest that different life-history stages interact to influence telomere length, and that migratory patterns may be important determinants of variation in an individual's telomere dynamics.

scholarly journals Maternal Folate Concentration in Early Pregnancy and Newborn Telomere Length

2015 ◽  
Vol 66 (4) ◽  
pp. 202-208 ◽  
Author(s):  
Sonja Entringer ◽  
Elissa S. Epel ◽  
Jue Lin ◽  
Elizabeth H. Blackburn ◽  
Claudia Buss ◽  
...  
Keyword(s):  
Telomere Length ◽  
Developmental Plasticity ◽  
Mononuclear Cells ◽  
First Trimester ◽  
Serum Folate ◽  
Dna Integrity ◽  
Cell Physiology ◽  
Prospective Longitudinal Study ◽  
Telomere Biology ◽  
Prospective Longitudinal

Background/Aims: Telomere biology plays a fundamental role in genomic integrity and cell physiology. The newborn setting of telomere length (TL) likely has important implications for telomere dynamics over the lifespan; however, its determinants are poorly understood. Folate is essential for DNA integrity. The maternal compartment is the only source of folate for the developing fetus. We, therefore, tested the hypothesis that variation in maternal folate during pregnancy is associated with newborn TL. Methods: A prospective, longitudinal study was conducted in 119 mother-newborn dyads. Eligible mothers were enrolled at 9.5 (SD ±2.1) weeks gestation and followed through birth. Concentrations of maternal serum folate were measured in the first trimester of pregnancy. Newborn telomere length was measured in cord blood mononuclear cells (CBMC). Results: After accounting for the effects of other established determinants of newborn TL, each 10 ng/ml increase in maternal total folate was associated with a 5.8% increase in median TL (p = 0.03). The median TL in newborns of mother in the lowest quartile of total folate levels was approximately 10% shorter than that of newborns of mothers in the highest folate quartile. Conclusions: Our findings suggest that fetal TL exhibits developmental plasticity, and provide evidence that maternal nutrition may exert a ‘programming' effect on this system.

Rapid Telomere Loss in Hematopoietic Cells Associated with Development of t-MDS after Autologous Transplantation for Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2644-2644
Author(s):  
Sujata Chakraborty ◽  
C.-L. Sun ◽  
L. Francisco ◽  
A. Komiya ◽  
H. Damasco ◽  
...  
Keyword(s):  
Telomere Length ◽  
Hodgkin Lymphoma ◽  
Hematopoietic Cells ◽  
Myeloid Cells ◽  
Hematopoietic Cell ◽  
Initial Increase ◽  
Hematopoietic Stem ◽  
Telomere Regulation ◽  
Telomere Dynamics ◽  
Over Time

Abstract Therapy-related MDS (t-MDS) is a lethal complication of autologous hematopoietic cell transplantation (HCT) for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Although t-MDS is known to result from damage to hematopoietic stem cells (HSC) from genotoxic cancer treatment, the sequential cellular and molecular changes leading to its development are not known. To better understand t-MDS pathogenesis we are conducting a prospective study of a cohort of patients undergoing autologous HCT for HL and NHL. Patients are followed longitudinally from pre-HCT to 5 yrs post-HCT, with serial collection of marrow and blood samples. We investigated whether development of t-MDS after HCT was associated with altered telomere dynamics in hematopoietic cells. Telomeres are non-coding sequences at ends of chromosomes. Telomere shortening may be associated with genetic instability and myeloid leukemogenesis, and could predispose to t-MDS after HCT. Telomere length was measured in peripheral blood (PB) samples from 8 patients from the cohort who developed t-MDS after HCT and 24 matched controls who did not develop t-MDS (3 controls per case: matched for primary diagnosis, age at HCT, race and length of follow-up). Samples were analyzed pre-HCT and at d100, 6 months, 1 yr and then annually post-HCT till development of t-MDS. PB cells were mixed with equal numbers of 1301 cells, as internal controls, and hybridized with a telomere PNA-FITC probe. Relative telomere length (RTL) values (ratio of telomere signal of PB sample and control 1301 cells) were determined by flow cytometry (FlowFISH). RTL values of lymphoid and myeloid cells, identified by scatter properties, were separately analyzed. The median PBSC CD34+ count (106/kg) for cases was 4.9 (2.6–17.4) and controls was 5.2 (2.1–33.5). Differences in RTL were seen at several time points in t-MDS cases and controls for total cell, lymphoid and myeloid cells, but were most marked in the myeloid cells. Patients developing t-MDS showed reduced RTL pre-HCT (myeloid RTL: cases=18.2±4.8, controls=27.2±2.8); an increase in RTL at d 100 (myeloid RTL for cases=31.4±4.6, controls=19.6±2.5, p=0.04); and progressive reduction in RTL subsequently (myeloid RTL at 3 years: cases= 9.7±4.1, controls=22.0±2.2). An increase in RTL from pre-BMT to d 100 was seen in t-MDS patients (+16.0) but not in controls (−8.2) (p=0.004). A fixed effect growth curve model fitted to the data from d100 to 3 years to examine the rate of change in RTLs over time revealed a sharp decline in RTL for cases (β per 100 days = −1.93 for myeloid cells), but no change in RTL over time for controls (β = 0.07) (p = 0.02). In summary, we observed severely altered telomere dynamics in hematopoietic cells from patients who develop t-MDS post-HCT, with an initial increase in telomere length followed by a very sharp rate of telomere attrition till development of t-MDS. The initial increase in telomere length may reflect a need for increased recruitment of fresh HSC, with longer telomeres, to achieve hematopoietic recovery post-HCT. Subsequent rapid attrition of telomere length may reflect increased hematopoietic cell proliferation associated with ineffective hematopoiesis characteristic of MDS or represent altered telomere regulation in damaged HSC. Altered telomere regulation and reduced telomere length may contribute to leukemic transformation of HSC in t-MDS.

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