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 Early maternal separation is not associated with changes in telomere length in domestic kittens (Felis catus)

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11394
Author(s):  
Mikel Delgado ◽  
C.A. Tony Buffington ◽  
Melissa Bain ◽  
Dana L. Smith ◽  
Karen Vernau
Keyword(s):  
Telomere Length ◽  
Mixed Model ◽  
Maternal Separation ◽  
Linear Mixed Model ◽  
Quantitative Polymerase Chain Reaction ◽  
Single Copy ◽  
Felis Catus ◽  
Telomere Shortening ◽  
Orphan Status ◽  
Animal Rescue

Objective Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S). Results A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F1, 76.2 = 3.35, p = 0.07), orphan status (F1, 56.5 = 0.44, p = 0.51), time point (F1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.

scholarly journals Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity

2020 ◽  
Vol 9 (8) ◽  
pp. 2669 ◽  
Author(s):  
Máximo Bernabeu-Wittel ◽  
Raquel Gómez-Díaz ◽  
Álvaro González-Molina ◽  
Sofía Vidal-Serrano ◽  
Jesús Díez-Manglano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Telomere Length ◽  
Prospective Observational Study ◽  
Oxygen Species ◽  
Oxidative Stress Markers ◽  
Blood Leukocytes ◽  
Telomere Shortening ◽  
Blood Samples ◽  
Stress Markers ◽  
Total Antioxidant

Background: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. Methods: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. Results: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening (p = 0.001) were associated to death risk and to less survival days. Conclusions: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets.

Abstract 278: Diet-Induced Leukocyte Telomere Shortening Correlates with Extent of Atherosclerosis

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
GENESIO KARERE ◽  
Shifra Birnbaum ◽  
Clint Christensen ◽  
Michael Mahaney ◽  
John VandeBerg ◽  
...  
Keyword(s):  
Telomere Length ◽  
Pearson Correlation ◽  
Single Copy ◽  
Developed Countries ◽  
Primate Model ◽  
Telomere Shortening ◽  
Atherosclerotic Lesions ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Before And After

Introduction: Cardiovascular disease, the leading cause of death in developed countries, is commonly due to atherosclerosis. Studies have demonstrated association between leukocyte telomere shortening (LTS), extent of atherosclerotic lesions and accelerated cell senescence. Further LTS is associated with dietary intake. However, efforts to link LTS, diet and extent of lesions have been unsuccessful in humans due to difficulties controlling diet in large human population studies. To begin addressing these critical issues, we controlled dietary fat (high-fat, HF) in baboons for 2yrs - a well-developed primate model of human atherosclerosis. This is the first study in primates showing correlation of LTS with both chronic HF diet and atherosclerotic lesions. Hypothesis: We hypothesized that leukocyte telomere length decreased with chronic HF diet in baboons and is correlated with extent of atherosclerotic lesions. Methods and Results: A cohort of pedigreed baboons (n=107; females=46, males=61) was fed a HF diet for 2yrs. Absolute leukocyte telomere lengths (LTL; kb/diploid genome) were quantified by qPCR before and after diet challenge. Total telomere length was calculated by computing the ratio of telomere quantity per single copy gene quantity (baboon LIPG). Mean LTL was significantly shorter after feeding baboons a HF diet for 2 yrs (paired t test, p=0.03). Baboons (n=232) maintained on a low fat diet for 2yrs showed no significant difference in LTL (p=0.47). These findings suggest that a HF diet accelerates LTS. Further we quantified the extent of atherosclerotic lesions in baboons after 2yr HF diet and found that LTL, adjusted for age and sex, were correlated with lesions in descending aorta (Pearson correlation, r=0.19; p=0.03). Interestingly this correlation was significant in females but not in males after adjusting for age (r=0.27, p=0.03). Conclusions: LTS correlates with chronic feeding with a HF diet in baboons, is significantly correlated with arterial lesions and the correlation is sex-specific. These findings suggest that LTS may be a potential biomarker of extent of atherosclerosis.

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 GAPDH Pseudogenes and the Quantification of Feline Genomic DNA Equivalents

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
A. Katrin Helfer-Hungerbuehler ◽  
Stefan Widmer ◽  
Regina Hofmann-Lehmann
Keyword(s):  
Reference Gene ◽  
Copy Number ◽  
Genomic Dna ◽  
Single Copy ◽  
Variable Number ◽  
Suitable Reference Gene ◽  
Suitable Alternative ◽  
Future Studies ◽  
Gene Assay ◽  
Suitable Reference

Quantitative real-time PCR (qPCR) is broadly used to detect and quantify nucleic acid targets. In order to determine cell copy number and genome equivalents, a suitable reference gene that is present in a defined number in the genome is needed, preferably as a single copy gene. For most organisms, a variable number of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) pseudogenes have been reported. However, it has been suggested that a single-copy of the GAPDH pseudogene is present in the feline genome and that a GAPDH assay can therefore be used to quantify feline genomic DNA (gDNA). The aim of this study was to determine whether one or more GAPDH pseudogenes are present in the feline genome and to provide a suitable alternative qPCR system for the quantification of feline cell copy number and genome equivalents. Bioinformatics and sequencing results revealed that not just one but several closely related GAPDH-like sequences were present in the cat genome. We thus identified, developed, optimized, and validated an alternative reference gene assay using feline albumin (fALB). Our data emphasize the need for an alternative reference gene, apart from the GAPDH pseudogene, for the normalization of gDNA levels. We recommend using the fALB qPCR assay for future studies.

Increased Telomere Length Is a Negative a Predicting Factor for IST in Children with Severe Aplastic Anemia?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4381-4381
Author(s):  
Katarzyna Pawelec ◽  
Marek Janiak ◽  
Michał Matysiak ◽  
Pawel Krzysztof Wlodarski
Keyword(s):  
Aplastic Anemia ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Genomic Dna ◽  
Antithymocyte Globulin ◽  
Single Copy ◽  
Single Copy Gene ◽  
Blood Samples ◽  
Copy Gene ◽  
Predicting Factor

Abstract Abstract 4381 Shortening of telomeres is observed in 1/3 of peripheral blond samples, collected from patients with severe aplastic anemia (SAA). Probably, this phenomenon is associated with poor response to immunosuppressive therapy –IST (antithymocyte globulin -ATG and cyklosporin-CSA). The aim of this study was to assess the length of telomeres in peripheral blood of children with SAA treated with antithymocyte globulin (ATG) and cyklosporin (CSA) Materials and Methods: Peripheral blood samples were collected from 13 children with confirmed SAA. Patients (9 girls and 4 boys) aged 7–19 yrs have all received rabbit ATG in a dose of 3.75 mg/kg/day for 5 days and CSA in a dose of 5mg/kg/day for 12–14 months). Remission was assessed on 180th and 360th day of treatment. Control peripheral blood samples were obtained from 12 healthy children (3 girls and 9 boys, aged 3–17 yrs), 12 healthy adultand from 4 SAA children parents. Informed consent was obtained from all adult donors and from parents of participating children. DNA extraction and qPCR Genomic DNA was extracted from whole blood using AxyPrep Blood Genomic DNA Miniprep Kit (Axygene). Telomere length was determined using the quantitive PCR (qPCR) method described by Elisa Pavesi et al (1). Briefly, two qPCR reactions were run for each DNA sample: amplification of telomere product and amplification of a single copy gene (SEP15). Each qPCR reaction contained: Power SYBR1 Green PCR Master Mix (Applied Biosystems), template DNA and primers (270nM Tel1 and 900nM Tel2 or 500nM of each SEP15 primers). Telomere/single copy gene (T/S) ratios for samples were calculated using Human reference DNA (Applied Biosystems) standard curve. Reactions were preformed in Real Time PCR CFX96 system (Biorad). Statistica software version 9.1 (StatSoft) was used for statistical analysis Results: Among 13 SAA patients telomere shortening was found in 9 children while 4 patients had significantly elongated telomeres. All of the latter ones responded poorly to IST treatment: 3 of them did not respond (NR) to IST (neither on day 180 nor on 360) and one patient had a partial remission (PR). 2 patients in the NR group were randomized to unrelated bone marrow transplantation and one had another course of IST (no unrelated donor), after which he reached a PR. All patients with elongated telomeres had normal serum adriostendion level. Telomere elongation was also found in parents compared to the control group of adults (n=12, age range 31–57). Among 9 patients with shortened telomeres, 4 achieved complete remission (CR), 1 - PR and 4 did not respond (NR) to treatment on check times points. Conclusions: Our observations indicate that SAA patients with shortened telomeres respond to immunosuppressive therapy better then those with elongated telomeres. Telomere length may be considered therefore as a predicting factor in this patients. Studies on a larger group of patients should be performed to confirm our observations. Short telomere definition –samples, which T/S value is less than the first Quartile of controls. Long telomere - samples, which T/S value is in III quartile of controls. Very long telomere - samples, which T/S value is higher than the IV Quartile of controls. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hippocampal astroglial hypertrophy in mice subjected to early life maternal deprivation

2021 ◽  
Author(s):  
Arnab Nandi ◽  
Garima Virmani ◽  
Swananda Marathe
Keyword(s):  
Immune Responses ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Stratum Radiatum ◽  
Late Adulthood ◽  
Synaptic Physiology ◽  
And Behavior

Early-life stress (ELS), including chronic deprivation of maternal care, exerts persistent life-long effects on animal physiology and behavior, and is associated with several neurodevelopmental disorders. Long-lasting changes in neuronal plasticity and electrophysiology are documented extensively in the animal models of ELS. However, the role of astroglia in the lasting effects of ELS remains elusive. Astrocytes are intricately involved in the regulation of synaptic physiology and behavior. Moreover, astrocytes play a major role in the innate and adaptive immune responses in the central nervous system (CNS). The role of immune responses and neuroinflammation in the altered brain development and persistent adverse effects of ELS are beginning to be explored. Innate immune response in the CNS is characterized by a phenomenon called astrogliosis, a process in which astrocytes undergo hypertrophy, along with changes in gene expression and function. While the immune activation and neuroinflammatory changes concomitant with ELS, or in juveniles and young adults have been reported, it is unclear whether mice subjected to ELS exhibit astrogliosis-like alterations well into late-adulthood. Here, we subjected mice to maternal separation from postnatal day 2 to day 22 and performed comprehensive morphometric analysis of hippocampal astrocytes during late-adulthood. We found that the astrocytes in the stratum radiatum region of the CA1 hippocampal subfield from maternally separated mice exhibit significant hypertrophy as late as 8 months of age, revealing the crucial changes in astrocytes that manifest long after the cessation of ELS. This study highlights the persistence of neuroinflammatory changes in mice exposed to ELS.

scholarly journals Parental responsiveness moderates the association between early-life stress and reduced telomere length

2013 ◽  
Vol 25 (3) ◽  
pp. 577-585 ◽  
Author(s):  
A. Asok ◽  
K. Bernard ◽  
T. L. Roth ◽  
J. B. Rosen ◽  
M. Dozier
Keyword(s):  
High Risk ◽  
Telomere Length ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Early Adversity ◽  
Telomere Shortening ◽  
Parental Responsiveness ◽  
Responsive Parenting ◽  
High Risk Children

AbstractEarly-life stress, such as maltreatment, institutionalization, and exposure to violence, is associated with accelerated telomere shortening. Telomere shortening may thus represent a biomarker of early adversity. Previous studies have suggested that responsive parenting may protect children from the negative biological and behavioral consequences of early adversity. This study examined the role of parental responsiveness in buffering children from telomere shortening following experiences of early-life stress. We found that high-risk children had significantly shorter telomeres than low-risk children, controlling for household income, birth weight, gender, and minority status. Further, parental responsiveness moderated the association between risk and telomere length, with more responsive parenting associated with longer telomeres only among high-risk children. These findings suggest that responsive parenting may have protective benefits on telomere shortening for young children exposed to early-life stress. Therefore, this study has important implications for early parenting interventions.

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 Population differences in the length, early-life dynamics, and heritability of telomeres among European pied flycatchers

2021 ◽  
Author(s):  
Tiia Karkkainen ◽  
Toni Laaksonen ◽  
Malcolm Burgess ◽  
Alejandro Cantarero ◽  
Jesus Martinez-Padilla ◽  
...  
Keyword(s):  
Telomere Length ◽  
Early Life ◽  
Large Scale ◽  
Later Life ◽  
Sub Saharan Africa ◽  
Pied Flycatcher ◽  
Breeding Period ◽  
Population Differences ◽  
Telomere Shortening ◽  
Shortening Rate

Telomere length and shortening rate are increasingly used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Telomere length can be heritable, but both early-life conditions and later-life stressors can create variation in telomere shortening rate. Studies on between-population telomere length and dynamics are mostly lacking, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. Pied flycatcher (Ficedula hypoleuca) is a passerine bird spending the non-breeding period in sub-Saharan Africa but breeding across Eurasia (from Spain to western Siberia). Populations show marked differences in migration distance, genetics, breeding parameters, and egg components. We studied the large-scale variation of telomere length, early-life dynamics and heritability in the pied flycatcher by comparing six European populations across a north-south gradient (Finland, Estonia, England and Spain). There were clear population differences in telomere length, with English birds having the longest telomeres, followed by Spanish and lastly by Estonian and Finnish birds. Early-life telomere shortening rate tended to vary between populations, and faster nestling growth affected telomeres more negatively in northern than southern populations. The heritability of telomere length was moderate (h2 = 0.34 - 0.40), with stronger heritability to paternal than maternal telomere length. There was also evidence indicating that the level of paternal heritability could differ between populations. While the sources of between-population differences in telomere-related biology remain to be identified (i.e. genetics, environmental factors), our study illustrates the need to expand telomere studies at the between-population level.

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