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

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.

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

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.56 ◽

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.

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Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length

Psychological Medicine ◽

10.1017/s0033291713001657 ◽

2013 ◽

Vol 44 (4) ◽

pp. 723-729 ◽

Cited By ~ 12

Author(s):

S. L. van Ockenburg ◽

P. de Jonge ◽

P. van der Harst ◽

J. Ormel ◽

J. G. M. Rosmalen

Keyword(s):

Telomere Length ◽

Mixed Model ◽

Linear Mixed Model ◽

Smoking Status ◽

Quantitative Polymerase Chain Reaction ◽

Accelerated Aging ◽

Biological Marker ◽

Eysenck Personality Questionnaire ◽

Telomere Attrition

BackgroundTelomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a biological marker of aging.MethodParticipants were 3432 adults (mean age 52.9 years, range 32–79). Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Neuroticism was assessed using the 12-item neuroticism scale of the Revised Eysenck Personality Questionnaire (EPQ-R) at T2 and T3. TL was measured by a monochrome multiplex quantitative polymerase chain reaction (PCR) assay at T1, T2 and T3. A linear mixed model was used to assess whether neuroticism could predict TL prospectively after adjusting for age, sex, body mass index (BMI), frequency of sports, smoking status, presence of chronic diseases and level of education.ResultsNeuroticism was a significant negative predictor of TL at follow-up (B = −0.004, p = 0.044) after adjusting for sex, age, baseline TL and various biological and lifestyle factors.ConclusionsHigh neuroticism is significantly and prospectively associated with telomere attrition independent of lifestyle and other risk factors.

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

Circulation Research ◽

10.1161/res.115.suppl_1.278 ◽

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.

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Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis

Children ◽

10.3390/children8090796 ◽

2021 ◽

Vol 8 (9) ◽

pp. 796

Author(s):

Audrey Monnin ◽

Amélie Vizeneux ◽

Nicolas Nagot ◽

Sabrina Eymard-Duvernay ◽

Nicolas Meda ◽

...

Keyword(s):

Telomere Length ◽

Quantitative Polymerase Chain Reaction ◽

Safety Data ◽

Poor Growth ◽

Telomere Shortening ◽

Motor Abilities ◽

Hiv Exposed ◽

One Year ◽

Hiv Acquisition ◽

Exposed Uninfected

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = −3.61, 95%CI: −7.08, −0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.

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Association Between Dietary Selenium Intake and Leukocyte Telomere Length in a Nationally Representative Sample of US Adults (OR11-06-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.or11-06-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Buyun Liu ◽

Yangbo Sun ◽

Guifeng Xu ◽

Shuang Rong ◽

Wei Bao

Keyword(s):

Telomere Length ◽

Representative Sample ◽

Quantitative Polymerase Chain Reaction ◽

Antioxidant Properties ◽

Biological Aging ◽

Leukocyte Telomere Length ◽

Telomere Shortening ◽

Dietary Selenium ◽

Selenium Intake ◽

Nationally Representative

Abstract Objectives DNA damage induced by oxidative stress is implicated in accelerated telomere shortening, a biomarker of biological aging. Although selenium has antioxidant properties, its impact on telomere length is largely unknown. This study aimed to examine the association between dietary selenium intake and leukocyte telomere length in a nationally representative sample of US adults. Methods We included 7409 adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Dietary selenium intake was calculated using data collected in the 24-hour dietary recall. Leukocyte telomere length was assayed using the quantitative polymerase chain reaction method. The association between selenium intake and telomere length was estimated by weighted linear regression models adjusting for demographic, socioeconomic and lifestyle factors, body mass index, supplements intake, and leukocyte cell type composition. Results The average dietary selenium intake was 109.1 mg/d (standard error [SE] 1.15). We didn't find a significant association between dietary selenium intake and telomere length in US adults. The average telomere length (SE) was 1.01 (0.02), 1.01 (0.01), and 1.04 (0.01) across increasing tertiles of dietary selenium intake. However, a significant interaction was observed for age (P = 0.02). Among individuals aged 20–44 years, the β coefficient of log-transformed telomere length, compared to lowest tertile of dietary selenium intake, was −0.041 (SE 0.012, P = 0.002) and −0.033 (SE 0.018, P = 0.07) for middle tertile and the highest tertile of selenium intake, respectively. The corresponding β coefficient was 0.009 (SE 0.016, P = 0.59) and −0.001 (SE 0.012, P = 0.95), respectively, for adults 45–64 years old, and 0.017 (SE 0.015, P = 0.28) and 0.059 (SE 0.021, P = 0.01), respectively, for those aged 65 years or older. The results were not appreciably changed even after additionally adjustment for dietary intake of vitamin A, vitamin E, and zinc. Conclusions The association between dietary selenium intake and telomere length differed significantly by age groups, indicating that higher selenium intake may prevent telomere shortening in older adults but not in younger or middle-aged adults. Further studies about the underlying mechanisms are warranted. Funding Sources NA.

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Parallel telomere shortening in multiple body tissues owing to malaria infection

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2016.1184 ◽

2016 ◽

Vol 283 (1836) ◽

pp. 20161184 ◽

Cited By ~ 33

Author(s):

Muhammad Asghar ◽

Vaidas Palinauskas ◽

Nadège Zaghdoudi-Allan ◽

Gediminas Valkiūnas ◽

Andrey Mukhin ◽

...

Keyword(s):

Telomere Length ◽

Quantitative Polymerase Chain Reaction ◽

Telomere Shortening ◽

Tissue Samples ◽

Telomere Attrition ◽

Body Tissues ◽

Increased Risk ◽

Avian Malaria Parasite ◽

Systemic Stress ◽

The Impact

Several studies have shown associations between shorter telomere length in blood and weakened immune function, susceptibility to infections, and increased risk of morbidity and mortality. Recently, we have shown that malaria accelerates telomere attrition in blood cells and shortens lifespan in birds. However, the impact of infections on telomere attrition in different body tissues within an individual is unknown. Here, we tested whether malarial infection leads to parallel telomere shortening in blood and tissue samples from different organs. We experimentally infected siskins ( Spinus spinus ) with the avian malaria parasite Plasmodium ashfordi , and used real-time quantitative polymerase chain reaction (PCR) to measure telomere length in control and experimentally infected siskins. We found that experimentally infected birds showed faster telomere attrition in blood over the course of infection compared with control individuals (repeatedly measured over 105 days post-infection (DPI)). Shorter telomeres were also found in the tissue of all six major organs investigated (liver, lungs, spleen, heart, kidney, and brain) in infected birds compared with controls at 105 DPI. To the best of our knowledge, this is the first study showing that an infectious disease results in synchronous telomere shortening in the blood and tissue cells of internal organs within individuals, implying that the infection induces systemic stress. Our results have far-reaching implications for understanding how the short-term effects of an infection can translate into long-term costs, such as organ dysfunction, degenerative diseases, and ageing.

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Stress reactivity elicits a tissue-specific reduction in telomere length in ageing zebrafish (Danio rerio)

10.1101/2020.04.17.046599 ◽

2020 ◽

Author(s):

James R. Evans ◽

Jose V. Torres-Pérez ◽

Maria Elena Miletto Petrazzini ◽

Riva Riley ◽

Caroline H. Brennan

Keyword(s):

Telomere Length ◽

Stress Reactivity ◽

Quantitative Polymerase Chain Reaction ◽

Heart Tissue ◽

Telomere Shortening ◽

Tissue Specific ◽

Age Related ◽

Specific Manner ◽

Polymerase Chain ◽

The Relationship

ABSTRACTTelomere length reflects cellular ageing. Increased telomere shortening in leukocytes is associated with a range of neurodegenerative and cardiovascular diseases, the onset and progression of which may be mediated by behavioural traits such as anxiety and stress reactivity. However, the effects of the hypothalamus-pituitary-adrenal axis stress response are shown to be tissue specific. As such, leukocyte telomere length may not give an accurate measure of the relationship between stress-reactivity and telomere length in disease relevant tissues. To test the hypothesis that stress-reactivity contributes to age-related telomere shortening in a tissue specific manner, we examined the correlation between telomere length in heart and brain tissue and stress-reactivity in a population of young (6-9 month) and ageing (18 month) zebrafish. Stress-reactivity was assessed by tank diving, a zebrafish version of the rodent open-field test, and through gene expression. Telomere length was assessed using quantitative polymerase chain reaction. We show that ageing zebrafish have shorter telomeres in both heart and brain. Telomere length is inversely related to stress-reactivity in heart but not brain of ageing individuals. These data support the hypotheses that an anxious predisposition contributes to telomere shortening in heart tissue, and by extension age-related heart disease, and that stress-reactivity contributes to age-related telomere shortening in a tissue-specific manner.

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Telomere Length Calibration from qPCR Measurement: Limitations of Current Method

Cells ◽

10.3390/cells7110183 ◽

2018 ◽

Vol 7 (11) ◽

pp. 183 ◽

Cited By ~ 8

Author(s):

Youjin Wang ◽

Sharon Savage ◽

Rotana Alsaggaf ◽

Geraldine Aubert ◽

Casey Dagnall ◽

...

Keyword(s):

Telomere Length ◽

Quantitative Polymerase Chain Reaction ◽

Current Method ◽

Single Copy ◽

Health And Nutrition ◽

Healthy Donors ◽

Data Configuration ◽

Clinical Interest ◽

Age Range

Telomere length (TL) comparisons from different methods are challenging due to differences in laboratory techniques and data configuration. This study aimed to assess the validity of converting the quantitative polymerase chain reaction (qPCR) telomere/single copy gene (T/S) ratio to TL in kilobases (kb). We developed a linear regression equation to predict TL from qPCR T/S using flow cytometry with fluorescence in situ hybridization (flow FISH) TL data from 181 healthy donors (age range = 19–53) from the National Marrow Donor Program (NMDP) biorepository. TL measurements by qPCR and flow FISH were modestly correlated (R2 = 0.56, p < 0.0001). In Bland-Altman analyses, individuals with the shortest (≤10th percentile) or longest (≥90th) flow FISH TL had an over- or under-estimated qPCR TL (bias = 0.89 and −0.77 kb, respectively). Comparisons of calculated TL from the NMDP samples and 1810 age- and sex-matched individuals from the National Health and Nutrition Examination Survey showed significant differences (median = 7.1 versus 5.8 kb, respectively, p < 0.0001). Differences in annual TL attrition were also noted (31 versus 13 bp/year, respectively, p = 0.02). Our results demonstrate that TL calculated in kb from qPCR T/S may yield biased estimates for individuals with the shortest or longest TL, those often of high clinical interest. We also showed that calculated TL in kb from qPCR data are not comparable across populations and therefore are not necessarily useful.

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Association Between Telomere Shortening and Ageing During Occupational Exposure

Journal of Medical Biochemistry ◽

10.2478/v10011-012-0005-2 ◽

2012 ◽

Vol 31 (3) ◽

pp. 211-216 ◽

Cited By ~ 7

Author(s):

Sima Eshkoor ◽

Fatemeh Jahanshiri ◽

Patimah Ismail ◽

Sabariah Rahman ◽

Saidi Moin ◽

...

Keyword(s):

Occupational Exposure ◽

Telomere Length ◽

Single Copy ◽

Accelerated Ageing ◽

Telomere Shortening ◽

Relative Telomere Length ◽

Accelerate Ageing ◽

Buccal Epithelial Cells ◽

Exposed Workers ◽

The Difference

Association Between Telomere Shortening and Ageing During Occupational ExposureTelomere length is considered as a biomarker of ageing, resulting in shortening during the process. The present investigation was an attempt to determine the relative telomere length in mechanical workshop workers. Telomere length shortening in cells during occupational exposure causes accelerated ageing. Genomic DNA was isolated from buccal epithelial cells collected from 240 individuals, comprising two groups of 120 exposed workers and 120 unexposed controls. Telomere length was measured by using real time PCR. Both telomere (T) and single copy gene (S) specific primers were used to compute the relative T/S ratio and expressed as the relative telomere length. Telomere length differed significantly between the workers and controls (p<0.05). The results showed an indirect and significant association (r=-0.356, p=0.001) between age and telomere length in the workers. This study showed that the difference in telomere length shortening was statistically significant (p<0.05) between the workers and controls. It was concluded that occupational exposure acts as a risk factor to enhance telomere length shortening and accelerate ageing.

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Analyzing discontinuities in longitudinal count data: A multilevel generalized linear mixed model.

Psychological Methods ◽

10.1037/met0000347 ◽

2020 ◽

Author(s):

James L. Peugh ◽

Sarah J. Beal ◽

Meghan E. McGrady ◽

Michael D. Toland ◽

Constance Mara

Keyword(s):

Count Data ◽

Mixed Model ◽

Linear Mixed Model ◽

Generalized Linear Mixed Model ◽

Longitudinal Count Data

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