scholarly journals Association of Leukocyte Telomere Length With Perceived Physical Fatigability

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 207-208
Author(s):  
Joseph Zmuda ◽  
Joseph Lee ◽  
Lawrence Honig ◽  
Kaare Christensen ◽  
Mary Feitosa ◽  
...  
Keyword(s):  
Telomere Length ◽  
Family Study ◽  
Functional Decline ◽  
Prognostic Indicator ◽  
Health Conditions ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Potential Marker ◽  
Two Generations

Abstract Leukocyte telomere length (LTL) is a potential marker of biological aging, but its relationship to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability. Two generations of participants (N=1,997; 309 probands, 1,688 offspring) were from the Long Life Family Study (age=73.7±10.4, range 60-108, 54.4% women). LTL was assayed at baseline and 8.0±1.1 years later perceived physical fatigability was measured using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0-50, higher scores=greater fatigability). Prevalence of greater physical fatigability (PFS scores≥15) was 41.9%. Using multivariate linear regression, one kilobase pair shorter LTL predicted higher PFS Physical scores (β=0.9, p=0.025), adjusted for family relatedness, generation (indicator for age), field center, follow-up time, sex, and follow-up body mass index, physical activity, health conditions. LTL, a promising marker of future fatigability, may allow for early identification of those at-risk for deleterious aging.

Abstract 16704: Leukocyte Telomere Length and Risk of Stroke: The Strong Heart Family Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Caroline Goode ◽  
Jinying Zhao ◽  
Richard B Devereux ◽  
Santosh Murthy ◽  
Alexander E Merkler ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Telomere Length ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Potential Biomarker ◽  
Primary Model ◽  
Strong Heart Family Study

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.

scholarly journals Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants

2020 ◽  
Vol 26 (9) ◽  
pp. 906-917
Author(s):  
Adiba Ashrafi ◽  
Stephanie Cosentino ◽  
Min S. Kang ◽  
Joseph H. Lee ◽  
Nicole Schupf ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Telomere Length ◽  
Semantic Processing ◽  
Family Study ◽  
Clinical Information ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Information Processing Speed ◽  
Long Life ◽  
Study Participants

AbstractObjective:Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.Method:Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage.Results:Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005).Conclusions:Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population.

Abstract P276: Metabolic Profiles of Biological Aging in American Indians: The Strong Heart Family Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
Jiang He ◽  
Jue Lin ◽  
Tet Matsuguchi ◽  
Elizabeth Blackburn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Telomere Length ◽  
American Indians ◽  
Multiple Testing ◽  
Family Study ◽  
Biological Aging ◽  
Metabolic Profiles ◽  
Leukocyte Telomere Length ◽  
Age Related ◽  
Strong Heart Family Study

Background: Telomere length is an emerging biomarker for cellular senescence or biological aging. Short leukocyte telomere length (LTL) has been associated with a wide range of age-related metabolic disorders such as diabetes and cardiovascular disease. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolic profiles of biological aging assessed by telomere length in human. Objective: To identify metabolic profiles of leukocyte telomere length in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003). Methods: This study included 432 SHFS participants free of cardiovascular disease and type 2 diabetes. LTL was measured by quantitative polymerase chain reaction (qPCR). Plasma metabolites were detected using an untargeted metabolomics approach by high-resolution liquid chromatography-mass spectrometry (LC/MS). The association of leukocyte telomere length with concentration of each metabolite was examined using generalized estimating equation (GEE), adjusting for age, sex, study center, body mass index, fasting glucose and fasting insulin. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: After adjusting for covariates and multiple testing, three metabolites including cytosine, selenophosphate and pentyl propanoate, were significantly associated with LTL. Of these, cytosine was positively associated with LTL (β=0.0476, 95% CI, 0.0474 to 0.0478, P=1.90х10-7), and selenophosphate (β =-0.1522, 95% CI, -0.1525 to -0.1519, P=2.48х10-8) and pentyl propanoate (β =-0.0644, 95% CI, -0.0683 to -0.0606, P=1.08х10-8) were negatively associated with LTL. Multivariate analysis demonstrated that participants with longer (top telomere tertile) and shorter (bottom telomere tertile) LTL can be clearly separated by partial least square discriminant analysis (PLS-DA) using these three metabolites. Multiple unknown compounds were also independently associated with LTL. Conclusions: This study, for the first time, identifies metabolites and metabolic profiles associated with interindividual variability in leukocyte telomere length, independent of potential confounders. Our findings provide novel insights into understanding of telomere biology and metabolic mechanisms underlying age-related disorders.

Short telomere length in blood leucocytes contributes to the presence of atherothrombotic stroke and haemorrhagic stroke and risk of post-stroke death

2013 ◽  
Vol 125 (1) ◽  
pp. 27-43 ◽  
Author(s):  
Weili Zhang ◽  
Yu Chen ◽  
Yuyao Wang ◽  
Peng Liu ◽  
Mei Zhang ◽  
...  
Keyword(s):  
Telomere Length ◽  
Haemorrhagic Stroke ◽  
Stroke Recurrence ◽  
Biological Aging ◽  
Post Stroke ◽  
Paired Samples ◽  
Potential Marker ◽  
Increased Risk ◽  
Stroke Death

Inter-individual differences in biological aging could affect susceptibility to stroke. To date, the relationship between stroke and telomere shortening remain inconclusive; and sparse data are available for haemorrhagic stroke. A Chinese case-control study was conducted, comprising 1756 cases (767 atherothrombosis, 503 lacunar infarction and 486 haemorrhagic strokes) and 1801 controls. Stroke patients were prospectively followed up for a median of 4.5 (range, 0.1–6.0) years. Individuals with shorter telomere length had a higher presence of atherothrombotic stroke {multivariate OR (odds ratio) 1.37 [95% CI (confidence interval), 1.06–1.77]; P=0.015} or haemorrhagic stroke [multivariate OR 1.48 (95% CI, 1.08–2.02); P=0.016] in comparison of the lowest to highest tertile of telomere length. Particularly, in subjects with a family history of stroke, there was a significant 2.55-fold increased presence of atherothrombotic stroke (95% CI, 1.87–3.48; Ptrend<0.0001) and a 2.33-fold increased presence of haemorrhagic stroke (95% CI, 1.62–3.36; Ptrend<0.0001). During the follow-up, 338 recurrent strokes and 312 deaths (181 from stroke or coronary heart disease and 131 from other causes) were documented. Associations with stroke recurrence were not observed in the follow-up patients, whereas atherothrombotic stroke cases with shorter telomeres had 69% increased risk of post-stroke death [relative risk, 1.69 (95% CI, 1.07–2.67); P=0.02]. Finally, we compared telomere lengths in 12 paired samples of circulating leucocytes and carotid atherosclerotic plaques from patients undergoing carotid endarterectomy; there was a positive correlation between vessel wall tissue and leucocyte telomere length. In conclusion, shorter telomere length may serve as a potential marker for the presence of atherothrombotic and haemorrhagic stroke and for the risk of post-stroke death.

scholarly journals Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study

2019 ◽  
Vol 246 ◽  
pp. 311-318 ◽  
Author(s):  
Maria Grau-Perez ◽  
Jinying Zhao ◽  
Brandon Pierce ◽  
Kevin A. Francesconi ◽  
Walter Goessler ◽  
...  
Keyword(s):  
American Indian ◽  
Telomere Length ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Strong Heart Family Study

scholarly journals Analysis of the Association Between TERC and TERT Genetic Variation and Leukocyte Telomere Length and Human Lifespan—A Follow-Up Study

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 82 ◽  
Author(s):  
Daniela Scarabino ◽  
Martina Peconi ◽  
Franca Pelliccia ◽  
Rosa Maria Corbo
Keyword(s):  
Genetic Variation ◽  
Telomere Length ◽  
Elderly Subjects ◽  
Mortality Data ◽  
Leukocyte Telomere Length ◽  
Age Classes ◽  
Follow Up Study ◽  
Human Lifespan ◽  
The Difference

We investigated the possible influence of TERC and TERT genetic variation and leukocyte telomere length (LTL) on human lifespan. Four polymorphisms of TERT and three polymorphisms of TERC were examined in a sample of elderly subjects (70–100 years). After nine years of follow-up, mortality data were collected, and sub-samples of long-lived/not long-lived were defined. TERT VNTR MNS16A L/L genotype and TERT rs2853691 A/G or G/G genotypes were found to be associated with a significantly higher risk to die before the age of 90 years, and with a significantly lower age at death. The association between lifespan and LTL at baseline was analyzed in a subsample of 163 subjects. Age at baseline was inversely associated with LTL (p < 0.0001). Mean LTL was greater in the subjects still living than in those no longer living at follow-up (0.79 T/S ± 0.09 vs 0.63 T/S ± 0.08, p < 0.0001). Comparison of age classes showed that, among the 70–79-year-olds, the difference in mean LTL between those still living and those no longer living at follow-up was greater than among the 80–90-year-olds. Our data provide evidence that shorter LTL at baseline may predict a shorter lifespan, but the reliability of LTL as a lifespan biomarker seems to be limited to a specific age (70–79 years).

scholarly journals 0330 : Fixed ranking of leukocyte telomere length in elderly people: results from 8 year follow-up of the ADELAHYDE cohort

2015 ◽  
Vol 7 (2) ◽  
pp. 144
Author(s):  
Simon Toupance ◽  
Ghassan Watfa ◽  
Cécile Lakomy ◽  
Anna Kearney-Schwartz ◽  
Carlos Labat ◽  
...  
Keyword(s):  
Telomere Length ◽  
Elderly People ◽  
Leukocyte Telomere Length

scholarly journals Quantification of the pace of biological aging in humans through a blood test: The DunedinPoAm DNA methylation algorithm

2020 ◽  
Author(s):  
DW Belsky ◽  
A Caspi ◽  
L Arseneault ◽  
A Baccarelli ◽  
D Corcoran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Functional Decline ◽  
Longitudinal Change ◽  
Biological Aging ◽  
Early Life Adversity ◽  
Progressive Decline ◽  
System Integrity ◽  
Aging Study ◽  
Point Measure

ABSTRACTBiological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed to serve as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood DNA-methylation measure that is sensitive to variation in the pace of biological aging among individuals born the same year. We first modeled longitudinal change in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in the Dunedin birth cohort. Rates of change in each biomarker were composited to form a measure of aging-related decline, termed Pace of Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace of Aging, called DunedinPoAm for Dunedin (P)ace (o)f (A)ging (m)ethylation. Validation analyses showed DunedinPoAm was associated with functional decline in the Dunedin Study and more advanced biological age in the Understanding Society Study, predicted chronic disease and mortality in the Normative Aging Study, was accelerated by early-life adversity in the E-risk Study, and DunedinPoAm prediction was disrupted by caloric restriction in the CALERIE trial. DunedinPoAm generally outperformed epigenetic clocks. Findings provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

scholarly journals Leukocyte telomere length in patients with multiple sclerosis and its association with clinical phenotypes

2020 ◽  
Author(s):  
Michael Hecker ◽  
Brit Fitzner ◽  
Kathrin Jäger ◽  
Jan Bühring ◽  
Margit Schwartz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Telomere Shortening ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Age And Sex

AbstractAging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS.We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS) and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex.The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis.Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.Research in contextEvidence before this studyThere is a growing research interest in the relationship between age and the pathophysiology and clinical presentation of multiple sclerosis (MS). Telomere shortening is a hallmark of biological aging. However, the role of telomeres in this chronic immune-mediated neurodegenerative disease has not yet been widely studied. Two research groups provided evidence that the telomeres of immune cells in the peripheral blood are shorter in patients with MS than in healthy subjects.Added value of this studyWe found that leukocytes from patients with relapsing-remitting MS (RRMS) are characterized by relatively short telomere lengths (TL). On average, we observed 18% shorter TL in the RRMS patient cohort (n=40) than in the age- and sex-matched healthy control cohort (n=60). We further analyzed the association of TL and long-term clinical outcomes. RRMS patients with shorter TL had a higher rate of converting to secondary progressive MS over a 10-year follow-up period.Implications of all the available evidenceAs we and others have shown, TL are generally shorter in MS patients and associated with disease progression, independent of age. These findings suggest a link between biological aging and the heterogeneous clinical course of MS patients. It currently remains unclear whether shortened telomeres in MS are a cause or a consequence of the pathophysiological processes. Further studies with larger patient cohorts and different cell populations will be needed to expand our knowledge of age-related disease mechanisms and the use of TL as a biomarker in MS.

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