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 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.

scholarly journals The views of public and clinician stakeholders on risk assessment tools for post-stroke dementia: a qualitative study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025586 ◽  
Author(s):  
Eugene Tang ◽  
Catherine Exley ◽  
Christopher Price ◽  
Blossom Stephan ◽  
Louise Robinson
Keyword(s):  
Risk Assessment ◽  
Qualitative Study ◽  
Secondary Care ◽  
Assessment Tools ◽  
Stroke Patients ◽  
Post Stroke ◽  
North East ◽  
Increased Risk ◽  
Diagnosis Of Dementia

ObjectiveStroke-survivors are at increased risk of future dementia. Assessment to identify those at high risk of developing a disease using predictive scores has been utilised in different areas of medicine. A number of risk assessment scores for dementia have been developed but none has been recommended for use clinically. The aim of this qualitative study was to assess the acceptability and feasibility of using a risk assessment tool to predict post-stroke dementia.DesignQualitative semi-structured interviews were conducted and analysed thematically. The patients and carers were offered interviews at around 6 (baseline) and 12 (follow-up) months post-stroke; clinicians were interviewed once.SettingThe study was conducted in the North-East of England with stroke patients, family carers and healthcare professionals in primary and secondary care.ParticipantsThirty-nine interviews were conducted (17 clinicians and 15 stroke patients and their carers at baseline. Twelve stroke patients and their carers were interviewed at follow-up, some interviews were conducted in pairs).ResultsBarriers and facilitators to risk assessment were discussed. For the patients and carers the focus for facilitators were based on the outcomes of risk assessment for example assistance with preparation, diagnosis and for reassurance. For clinicians, facilitators were focused on the process that is, familiarity in primary care, resource availability in secondary care and collaborative care. For barriers, both groups focused on the outcome including for example, the anxiety generated from a potential diagnosis of dementia. For the patients/carers a further barrier included concerns about how it may affect their recovery. For clinicians there were concerns about limited interventions and how it would be different from standard care.ConclusionsRisk assessment for dementia post-stroke presents challenges given the ramifications of a potential diagnosis of dementia. Attention needs to be given to how information is communicated and strategies developed to support the patients and carers if risk assessment is used.

scholarly journals Shorter Telomere Length in Carriers of APOE-ε4 and High Plasma Concentration of Glucose, Glyoxal and Other Advanced Glycation End Products (AGEs)

2019 ◽  
Vol 75 (10) ◽  
pp. 1894-1898 ◽  
Author(s):  
Varinderpal S Dhillon ◽  
Permal Deo ◽  
Ann Chua ◽  
Phil Thomas ◽  
Michael Fenech
Keyword(s):  
Risk Factor ◽  
Telomere Length ◽  
Advanced Glycation End Products ◽  
Biological Aging ◽  
Advanced Glycation ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products ◽  
Ε4 Allele

Abstract Apolipoprotein-ε4 (APOE-ε4)—common variant is a major genetic risk factor for cognitive decline and Alzheimer's disease (AD). An accelerated rate of biological aging could contribute to this increased risk. Glycation of serum proteins due to excessive glucose and reactive oxygen species leads to the formation of advanced glycation end products (AGEs)—a risk factor for diabetes and AD, and decline in motor functioning in elderly adults. Aim of present study was to investigate impact of APOE-ε4 allele containing genotype and accumulation of AGEs in plasma on telomere length (TL). Results showed that TL is significantly shorter in APOE-ε4 carriers compared with non-APOE-ε4 carriers (p = .0003). Higher plasma glucose level was associated with shorter TL irrespective of APOE-ε4 allele containing genotype (r = −.26; p = .0004). With regard to AGEs, higher plasma glyoxal and fluorescent AGEs concentrations were inversely related to TL (r = −.16; p = .03; r = −.28; p = .0001), however, plasma Nε-(carboxymethyl)lysine levels didn't correlate with TL (r = −.04; p = .57). Results support the hypotheses that APOE-ε4 carriers have shorter telomeres than noncarriers and telomere erosion is increased with higher concentration of glucose, fluorescent AGEs, and glyoxal.

Closure of patent foramen ovale in “cryptogenic” stroke: Has the story come to an end?

2018 ◽  
Vol 13 (3) ◽  
pp. 240-242 ◽  
Author(s):  
Jean-Louis Mas ◽  
Gilles Chatellier
Keyword(s):  
Antiplatelet Therapy ◽  
Patent Foramen Ovale ◽  
Oral Anticoagulants ◽  
Cryptogenic Stroke ◽  
Stroke Recurrence ◽  
Foramen Ovale ◽  
Permanent Disability ◽  
Increased Risk ◽  
Procedural Complications

Contrasting with three randomized trials that failed to show any superiority of patent foramen ovale closure over antithrombotic therapy, two trials recently reported lower rates of stroke recurrence among patients assigned to patent foramen ovale closure than among those assigned to antiplatelet therapy. In addition, one of the initially negative trials concluded in favor of patent foramen ovale closure after an extended follow-up period. A better selection of patients, the use of reference treatment groups that included patients who received antiplatelet therapy alone (rather than antiplatelet drugs or oral anticoagulants, according to physician preference), and a longer follow-up of patients, may explain the divergent findings across studies. Procedural complications were reported in 1.5% to 5.9% of the patients, none of which led to permanent disability or death. Patent foramen ovale closure was associated with an increased risk of new-onset atrial fibrillation in several studies and of venous thromboembolism in one study.

Abstract TP180: Ankle-brachial Index and Recurrent Stroke Risk: a Meta-analysis

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Thomas Liman ◽  
Ja Bin Hong ◽  
Christopher Leonards ◽  
Bob Siegerink ◽  
Matthias Endres
Keyword(s):  
Recurrent Stroke ◽  
Meta Analysis ◽  
Ankle Brachial Index ◽  
Stroke Recurrence ◽  
Significant Heterogeneity ◽  
Vascular Events ◽  
Vascular Death ◽  
Atherosclerotic Burden ◽  
Increased Risk

Background and Purpose: The ankle-brachial index (ABI) is a fast, cheap, non-invasive indicator of atherosclerotic burden that may also be indicative of stroke recurrence. In this systematic review and meta-analysis, we sought to explore ABI’s merit as a marker for stroke recurrence and vascular risk by synthesizing the data currently available in the stroke literature. Methods: We searched Embase, MEDLINE, and Pubmed databases for prospective cohort studies that included consecutive stroke and/or transient ischemic attack (TIA) patients, measured ABI at baseline, and performed a follow-up assessment at least 12 months following initial stroke/TIA. The following endpoints were chosen for our analysis: (1) recurrent stroke and (2) combined vascular endpoint (recurrent vascular event or vascular death). Crude risk ratios and adjusted Cox proportional hazard ratios (HRs) were combined separately using the random-effects model. Study level characteristics (e.g. percent of cohort with a history of hypertension, average cohort age, and mean follow-up duration) were included as meta-regression covariates. Results: We included 11 studies (5374 patients). Low ABI was associated with an increased risk of recurrent stroke (pooled estimated HR 1.70, 95% CI 1.10-2.64) and vascular events or vascular death, following stroke (pooled estimated HR 2.22, 95% CI 1.67-2.97). No significant heterogeneity was observed in the meta-analysis. Conclusion: Our results confirm the prognostic value of ABI for the recurrence of stroke. It is likely that the inclusion of ABI in risk calculation models will help in improving accuracy of existing models.

scholarly journals Risk of ischaemic stroke in patients with migraine: a longitudinal follow-up study using a national sample cohort in South Korea

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e027701 ◽  
Author(s):  
Sang-Yeon Lee ◽  
Jae-Sung Lim ◽  
Dong Jun Oh ◽  
Il Gyu Kong ◽  
Hyo Geun Choi
Keyword(s):  
South Korea ◽  
Ischaemic Stroke ◽  
Statistical Significance ◽  
Young Patients ◽  
Haemorrhagic Stroke ◽  
Control Group ◽  
Follow Up Study ◽  
Increased Risk ◽  
Migraine Group

ObjectiveAccumulating evidence has supported the association between migraine and stroke, but the causative association remains unclear. We aimed to investigate the risks of different types of stroke in patients with migraine.DesignA longitudinal follow-up study.SettingData collected from a national cohort between 2002 and 2013 by the South Korea Health Insurance Review and Assessment.ParticipantsWe extracted the data from patients with migraine (n=41 585) and 1:4 matched controls (n=1 66 340) and analysed the occurrence of ischaemic and haemorrhagic strokes. The migraine group included participants treated for migraine (International Classification of Disease-10 (ICD-10): G43)≥2 times. Haemorrhagic stroke (I60-I62) and ischaemic stroke (I63) were determined based on the admission histories. The crude and adjusted HRs were calculated using Cox proportional hazard models, and the 95% CI were determined. Subgroup analyses stratified by age and sex were also performed.ResultsHigher rates of ischaemic stroke were observed in the migraine group (2.3% [964/41,585]) than in the control group (2.0% [3294/166 340], P<0.001). The adjusted HR for ischaemic stroke was 1.18 (95% CI=1.10 to 1.26) in the migraine group (P<0.001). Compared with control subjects, participants who reported migraine with aura and migraine without aura had increased adjusted HRs of 1.44 (95% CI=1.09 to 1.89) and 1.15 (95% CI=1.06 to 1.24), respectively, for ischaemic stroke, but no increased risk of haemorrhagic stroke. In our subgroup analysis, a strong association between migraine and ischaemic stroke was observed in young patients, specifically young women. The contribution of migraine to the occurrence of ischaemic stroke was also observed in middle-aged women and old women (each P<0.05). The risk of haemorrhagic stroke did not reach statistical significance in any age group.ConclusionMigraine is associated with an increased risk of ischaemic stroke, but not haemorrhagic stroke.

scholarly journals The association between telomere length and ischemic stroke risk and phenotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ezgi Yetim ◽  
Mehmet Akif Topcuoglu ◽  
Nuket Yurur Kutlay ◽  
Ajlan Tukun ◽  
Kader K. Oguz ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Telomere Length ◽  
Infarct Volume ◽  
Chronological Age ◽  
Biological Aging ◽  
Lesion Volume ◽  
Blood Leukocytes ◽  
Scale Scores ◽  
Time Of Admission

AbstractThe chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70–5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.

scholarly journals Telomere length dynamics over 10-years and related outcomes in patients with COPD

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
E. Córdoba-Lanús ◽  
S. Cazorla-Rivero ◽  
M. A. García-Bello ◽  
D. Mayato ◽  
F. Gonzalvo ◽  
...  
Keyword(s):  
Lung Function ◽  
Gas Exchange ◽  
Telomere Length ◽  
Telomere Shortening ◽  
Lung Hyperinflation ◽  
Risk Of Death ◽  
Copd Patients ◽  
Increased Risk ◽  
Over Time

Abstract Background Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. Methods Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis. Results At baseline, T/S inversely correlated with age (r = − 0.236; p < 0.001), but there was no relationship between T/S and clinical and lung function variables (p > 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p < 0.0001; KCO p = 0.042; IC/TLC p < 0.0001; 6MWD p = 0.004 and BODE index p = 0.009). Patients in the lowest tertile of T/S through the follow-up period had an increased risk of death [HR = 5.48, (1.23–24.42) p = 0.026]. Conclusions This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.

scholarly journals Androgen Derivatives Improve Blood Counts and Elongate Telomere Length in Patients with Dyskeratosis Congenita

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2585-2585 ◽  
Author(s):  
Martin Kirschner ◽  
Monica Sofia Ventura Ferreira ◽  
Anne-Sophie Bouillon ◽  
Marcin W. Wlodarski ◽  
Michaela Schwarz ◽  
...  
Keyword(s):  
Telomere Length ◽  
Peripheral Blood ◽  
Research Funding ◽  
Somatic Mutations ◽  
Bone Marrow Failure ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Treatment Start ◽  
Increased Risk

Abstract Introduction: Classical Dyskeratosis Congenita (DKC) is a systemic disorder characterized mainly by mucocutaneous features and bone marrow failure. DKC is caused by mutations affecting proper telomere maintenance leading to premature telomere shortening. Clinically, assessment of telomere length (TL) is being used for screening and diagnosis of DKC. Previous studies showed that androgen derivatives (AD) such as danazol or oxymetholone can improve blood counts and reduce transfusion frequency in patients with DKC. Reports from in vitro studies suggest that AD can increase the expression of telomerase and elongate telomeres reversing at least partially the mutation-related haploinsufficiency of the telomerase complex. However, whether telomere elongation can be observed in vivo is still controversial. Patients with DKC have an increased risk of developing solid tumors and acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Malignant transformation occurs mostly by chromosomal instability mediated by critical short telomeres and not via clonal hematopoiesis (CHIP) and eventual selection for MDS-related somatic mutations. The question whether increased telomerase activity by AD increases the risk for additional MDS-related mutations is unclear. In our study, we aimed to investigate TL and MDS-related somatic mutations in DKC patients undergoing treatment with AD. Methods and Patients: 5 patients enrolled in the Aachen Telomeropathy Registry (ATR) that underwent AD treatment were included in the analysis. All patients had molecularly confirmed DKC (4 patients having mutations in TERC, 1 patient in TERT). TERC mutated patients received danazol treatment (mean dosage 625 mg per day) while the patient with TERT mutation was treated with low dose oxymetholone (0.22mg/kg) per day. Patients were at a median age of 43.1 (range from 21.7 to 53.8) years. Median duration of treatment with AD was 14 months (3 to 29 mo) and is actually ongoing in all patients treated with danazol. Follow-up for blood counts and TL length assessment was carried out after median 14 months after treatment start with AD. TL assessment and blood counts of the patient receiving oxymetholone was carried out at the end of AD treatment after 29 months. All patients underwent next-generation sequencing (NGS) analysis using custom NGS-panel including frequent genes implicated in MDS development. Quality parameters of the NGS analysis were satisfactory (Q30>85%) and 95% of the expected area was covered at minimum 300x. To minimize risk of detecting sequencing errors, a threshold of 10 (absolute) and 5% (relative) variant allele frequency (VAF) was chosen. TL assessment of peripheral blood granulocytes and lymphocytes was carried out by Flow-FISH and all results are given in kb. Results: Analysis of the peripheral blood counts revealed a significant increase in platelets counts from mean 56/nl ±50 S.D. before treatment to 88/nl ±49 (p=0.03) during treatment. Similar results were observed for leukocyte counts increasing significantly from 3.83/µl±1.86 to 4.70/µl±2.88 (p=0.04). Hemoglobin counts showed a non-significant increase from 8.9 g/dl ±2.6 to 10.2 g/dl ±2.9 (p=0.13, all student paired t-test). Focusing on TL, lymphocyte TL increased significantly from 4.32kb±0.47 to 5.13kb ±0.57 (p=0.001). TL in the granulocyte subpopulation increased from 4.73kb±0.33 before treatment start to 6.10kb±0.50 under treatment (p=0.026). Calculated median increase in TL per months for lymphocytes and granulocytes was 0.092 kb (0.019 to 0.223 kb) and 0.166 kb (0.019kb to 0.513kb). Finally, NGS analysis for possible MDS-related mutations did not reveal any mutations before and under AD treatment. Conclusions: Based on our data in this genetically homogenous cohort of 5 patients with mutations in the telomerease genes TERC and TERT and short TL, AD significantly improve blood counts and elongate telomeres in granulocytes and lymphocytes. No MDS-related somatic mutations were observed during telomerase activation with AD. Pending longer follow up, treatment with AD seems to represent an efficient and safe therapy for patients with TERT or TERC mutations. Whether AD persistently elongate telomeres in DKC patients and how much this is dependent on the underlying DKC-related mutation requires further investigation. Disclosures Kirschner: Basilea Pharmaceutica: Other: travel support; BMS: Consultancy; Bayer: Consultancy; Roche: Consultancy. Wilop:Medizinwelten-Services GmbH: Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel grant; Bristol-Myers Squibb: Honoraria. Brümmendorf:Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Novartis: Consultancy, Research Funding; Takeda: Consultancy; Merck: Consultancy. Beier:Gilead: Other: travel support; Celgene: Other: travel support.

scholarly journals Associations of Loneliness and Social Isolation with Healthspan and Lifespan in the US Health and Retirement Study

2020 ◽  
Author(s):  
Christopher L Crowe ◽  
Benjamin W Domingue ◽  
Gloria Hu ◽  
Katherine M Keyes ◽  
Dayoon Kwon ◽  
...  
Keyword(s):  
Older Adults ◽  
Social Isolation ◽  
Healthy Aging ◽  
National Sample ◽  
Biological Aging ◽  
Health And Retirement Study ◽  
Increased Risk ◽  
The Us ◽  
Retirement Study

Background. Loneliness and social isolation are emerging public health challenges for aging populations. Methods. We followed N=11,305 US Health and Retirement Study (HRS) participants aged 50-95 from 2006-2014 to measure persistence of exposure to loneliness and social isolation. We tested associations of longitudinal loneliness and social-isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018. Results. During follow-up, 18% of older adults met criteria for loneliness and, for 6%, symptoms persisted across two or more follow-up assessments. For social isolation, these fractions were 21% and 8%. HRS participants who experienced loneliness and social isolation were at increased risk for disease, disability, and mortality. Older adults experiencing persistent loneliness were at a 59% increased hazard of mortality compared to those who were never lonely. For social isolation, the increase was 28%. Effect-sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and social isolation also exhibited physiological indications of advanced biological aging (Cohen's-d for persistent loneliness and social isolation=0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence of symptoms was associated with increased risk. Conclusion. Deficits in social connectedness prevalent in a national sample of older adults in the US were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connection to interrupt experiences of loneliness may promote healthy aging.

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