CLOCK genetic variations are associated with age-related changes in sleep duration and brain volume

2021 ◽  
Author(s):  
Song E Kim ◽  
Soriul Kim ◽  
Hyeon Jin Kim ◽  
Regina E Y Kim ◽  
Sol Ah Kim ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Sleep Duration ◽  
Sleep Disturbances ◽  
Brain Volume ◽  
Brain Aging ◽  
Genetic Variations ◽  
Analysis Of Covariance ◽  
Imaging Data ◽  
Cross Sectional ◽  
Age Related

Abstract Background Although a connection between sleep disruption and brain aging has been documented, biological mechanisms need to be further clarified. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, CLOCK, have been linked to both aging-related sleep disturbances and neurodegenerative diseases. This study aims to investigate how CLOCK genetic variation associates with sleep duration changes and/or volumetric brain alteration. Methods This population-based cross-sectional study used data from the Korean Genome Epidemiology Study (KoGES), and analyzed sleep characteristics and genetic and brain imaging data in 2,221 subjects (mean 58.8±6.8 years, 50.2% male). Eleven single-nucleotide polymorphisms (SNPs) in CLOCK were analyzed using PLINK software v1.09 to test for their association with sleep duration and brain volume. Haplotype analysis was performed by using pair-wise linkage disequilibrium (LD) of CLOCK polymorphisms, and multivariate analysis of covariance was for statistical analysis. Results Decreased sleep duration was associated with several SNPs in CLOCK intronic regions, with the highest significance for rs10002541 (P=1.58x10 -5). Five SNPs with the highest significance (rs10002541-rs6850524-rs4580704- rs3805151-rs3749474) revealed that CGTCT was the most prevalent. In the major CGTCT haplotype, decreased sleep duration over time was associated with lower cortical volumes predominantly in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere. Conclusion CLOCK genetic variations could be involved in age-related sleep and brain volume changes.

scholarly journals Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort

2019 ◽  
Author(s):  
Maxwell L. Elliott ◽  
Daniel W. Belsky ◽  
Annchen R. Knodt ◽  
David Ireland ◽  
Tracy R. Melzer ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Birth Cohort ◽  
Brain Aging ◽  
Chronological Age ◽  
Biological Aging ◽  
Imaging Data ◽  
Cross Sectional ◽  
Cohort Differences ◽  
Age Related ◽  
The Brain

AbstractAn individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia, and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.

scholarly journals A Systematic Review on Cross-Cultural Comparative Studies of Sleep in Young Populations: The Roles of Cultural Factors

2021 ◽  
Vol 18 (4) ◽  
pp. 2005
Author(s):  
Mina Jeon ◽  
Dagmara Dimitriou ◽  
Elizabeth J. Halstead
Keyword(s):  
Cultural Values ◽  
Cultural Differences ◽  
Sleep Duration ◽  
Psychological Functioning ◽  
Sleep Disturbances ◽  
Cultural Factors ◽  
Cross Cultural ◽  
Cross Cultural Differences ◽  
Age Related ◽  
Systematic Understanding

Recent studies have shown that sleep is influenced and shaped by cultural factors, including cultural values, beliefs and practices. However, a systematic understanding of how cultural factors in countries may influence sleep duration and sleep disturbances is still lacking. Therefore, we focused on a comparison of sleep duration and disturbances in young populations between countries. We report cross-cultural differences between the child, parent and environmental factors, and their association with sleep duration and disturbances. The review is based on literature searches of seven databases published until December 2020. Studies were included if they investigated sleep duration and disturbances of individuals up to 18 years across at least two or more countries. The results of this review have shown that sleep duration and disturbances vary between countries and regions and certain factors (e.g., bedtime routines, sleeping arrangement, physical activity and psychological functioning) have been associated with sleep duration or disturbances. This review also demonstrates that certain factors which were associated with sleep duration or disturbances in one country, were not shown in other countries, suggesting a need for recommendations for age-related sleep duration and sleep interventions to consider cultural differences that influence sleep duration or disturbances in individual countries or regions.

scholarly journals Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

2012 ◽  
Vol 26 (11) ◽  
pp. 1808-1820 ◽  
Author(s):  
Lulu Mao ◽  
Robert T. Dauchy ◽  
David E. Blask ◽  
Lauren M. Slakey ◽  
Shulin Xiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Circadian Rhythm ◽  
Sleep Disturbances ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Glycogen Synthase ◽  
Human Breast ◽  
Light At Night ◽  
Mesenchymal Transition ◽  
Age Related

Abstract Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients.

scholarly journals Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Didac Vidal-Pineiro ◽  
Yunpeng Wang ◽  
Stine K Krogsrud ◽  
Inge K Amlien ◽  
William FC Baaré ◽  
...  
Keyword(s):  
Early Life ◽  
Brain Aging ◽  
Average Rate ◽  
Aging Brain ◽  
Imaging Data ◽  
Cross Sectional ◽  
Polygenic Scores ◽  
Longitudinal Imaging ◽  
Brain Age ◽  
Brain Change

Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

scholarly journals Sleep Duration and Excessive Daytime Sleepiness Are Associated with Obesity Independent of Diet and Physical Activity

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1219 ◽  
Author(s):  
Andrea Maugeri ◽  
Jose Medina-Inojosa ◽  
Sarka Kunzova ◽  
Antonella Agodi ◽  
Martina Barchitta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Sleep Duration ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Central Obesity ◽  
Sleep Disturbances ◽  
Short Sleep Duration ◽  
Cross Sectional ◽  
Short Sleep ◽  
Diet And Physical Activity

In the European Union, Czech Republic ranks 3rd and 6th for the incidence of obesity and cardiovascular diseases, respectively. Worldwide, short sleep duration and excessive daytime sleepiness (EDS) characterize obese subjects, which in turn exhibit scarce physical activity and unhealthy diet. We aimed to understand the relationship between irregular sleep patterns, obesity and lifestyle factors, such as diet and physical activity, in a vulnerable Czech population. 1482 members of the Kardiovize cohort, a random sample of the Czech urban population, were included in a cross-sectional study. Exposure variables included self-reported sleep duration and EDS, assessed by the Epworth Sleepiness Scale. Primary outcomes were BMI and waist-to-hip ratio or prevalence of obesity and central obesity. Covariates included physical activity and diet. Associations and interactions between variables were evaluated using logistic regression analyses. After adjustment for covariates, short sleep duration (<7 h) was associated with greater odds of overweight (BMI > 25; OR = 1.42; 95%CI = 1.06–1.90; p = 0.020) and obesity (BMI > 30; OR = 1.40; 95%CI = 1.02–1.94; p = 0.047), while EDS was associated with greater odds of central obesity (OR = 1.72; 95%CI = 1.06–2.79; p = 0.030), independent of diet and physical activity. However, due to the cross-sectional nature of our study, further prospective, large-scale studies are needed to evaluate the etiological link and causality between sleep disturbances and obesity.

scholarly journals Individual variations in “Brain age” relate to early life factors more than to longitudinal brain change

2021 ◽  
Author(s):  
D. Vidal-Piñeiro ◽  
Y. Wang ◽  
SK. Krogsrud ◽  
IK. Amlien ◽  
WFC. Baaré ◽  
...  
Keyword(s):  
Early Life ◽  
Brain Aging ◽  
Average Rate ◽  
Aging Brain ◽  
Individual Change ◽  
Imaging Data ◽  
Cross Sectional ◽  
Polygenic Scores ◽  
Longitudinal Imaging ◽  
Brain Age

AbstractBrain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher than expected brain age is thought partially to reflect above-average rate of brain aging. We explicitly tested this assumption in two large datasets and found no association between cross-sectional brain age and steeper brain decline measured longitudinally. Rather, brain age in adulthood was associated with early-life influences indexed by birth weight and polygenic scores. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

scholarly journals Sleep disturbances among pregnant women with history of migraines: A cross-sectional study

Cephalalgia ◽  
2015 ◽  
Vol 35 (12) ◽  
pp. 1092-1102 ◽  
Author(s):  
Chunfang Qiu ◽  
Ihunnaya O Frederick ◽  
Tanya Sorensen ◽  
Sheena K Aurora ◽  
Bizu Gelaye ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Pregnant Women ◽  
Sleep Duration ◽  
Sleep Disturbances ◽  
Cross Sectional Study ◽  
Poor Sleep ◽  
Sectional Study ◽  
Short Sleep Duration ◽  
Cross Sectional ◽  
History Of

Background Migraine is associated with sleep disturbances in men and non-pregnant women. However, relatively little is known about sleep disturbances among pregnant migraineurs. We investigated sleep disturbances among pregnant women with and without history of migraine. Methods This cross-sectional study was conducted among 1324 women who were recruited during early pregnancy. Migraine diagnoses were based on the International Classification of Headache Disorders-II criteria. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to evaluate sleep-related characteristics including sleep duration, sleep quality, excessive daytime sleepiness, and other sleep traits. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Results Migraineurs were more likely than non-migraineurs to report short sleep duration (<6.5 hours) (AOR = 1.47, 95% CI 1.07–2.02), poor sleep quality (PSQI>5) (AOR = 1.73, 95% CI 1.35–2.23), and daytime dysfunction due to sleepiness (AOR = 1.51, 95% CI 1.12–2.02). Migraineurs were also more likely than non-migraineurs to report taking sleep medication during pregnancy (AOR = 1.71, 95% CI 1.20–2.42). Associations were generally similar for migraine with or without aura. The odds of sleep disturbances were particularly elevated among pre-pregnancy overweight migraineurs. Conclusion Migraine headache and sleep disturbances are common comorbid conditions among pregnant women.

scholarly journals The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study

2003 ◽  
Vol 149 (2) ◽  
pp. 145-152 ◽  
Author(s):  
J Svartberg ◽  
M Midtby ◽  
KH Bonaa ◽  
J Sundsfjord ◽  
RM Joakimsen ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Linear Regression Analysis ◽  
Coffee Consumption ◽  
Free Testosterone ◽  
Lifestyle Factors ◽  
Analysis Of Covariance ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Cross Sectional ◽  
Age Related

OBJECTIVE: To study whether lifestyle factors and/or chronic disease are associated with the age-related decline of total and free testosterone in men, or if these factors might be associated with the variation of total and free testosterone but not with their age-related decline. DESIGN: A population-based, cross-sectional study was used. METHODS: Total testosterone and sex hormone binding globulin (SHBG) levels were analyzed and free testosterone levels were calculated in 1563 men participating in the Tromso study in 1994/1995. Anthropometric characteristics were also measured and two standardized questionnaires completed, including lifestyle factors and medical history. The data were analyzed with multiple linear regression analysis of covariance, and logistic regression. RESULTS: Total and free testosterone were inversely associated (P=0.001 and P<0.001), while SHBG was positively associated (P<0.001) with age. Body mass index (BMI) was inversely associated with total (P<0.001) and free (P=0.016) testosterone and SHBG (P<0.001). Both total and free testosterone were positively associated with tobacco consumption (P<0.001 and P=0.004) and total testosterone was positively associated with coffee consumption (P<0.001). SHBG was positively associated with smoking (P=0.004) and coffee consumption (P<0.001). Men who reported having had a stroke or having a cancer diagnosis had lower levels of total testosterone (P<0.001 and P<0.01) and free testosterone (P<0.01). CONCLUSIONS: BMI and smoking are independent contributors to the variation of total and free testosterone and SHBG levels, and coffee consumption to the variation of total testosterone and SHBG. Thus, lifestyle factors can have a direct effect on circulating levels of free endogenous sex hormones and to total levels due to the effect on SHBG levels.

scholarly journals Quantification of biological aging in young adults

2015 ◽  
Vol 112 (30) ◽  
pp. E4104-E4110 ◽  
Author(s):  
Daniel W. Belsky ◽  
Avshalom Caspi ◽  
Renate Houts ◽  
Harvey J. Cohen ◽  
David L. Corcoran ◽  
...  
Keyword(s):  
Young Adults ◽  
Brain Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Research Translation ◽  
Human Aging ◽  
Aging Research ◽  
Cross Sectional ◽  
Age Related ◽  
Organ Systems

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

scholarly journals Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness

Neurology ◽  
2019 ◽  
Vol 93 (11) ◽  
pp. e1045-e1057 ◽  
Author(s):  
Si Eun Kim ◽  
Jin San Lee ◽  
Sookyoung Woo ◽  
Seonwoo Kim ◽  
Hee Jin Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cortical Thickness ◽  
Cardiometabolic Risk ◽  
Brain Aging ◽  
Normal Weight ◽  
Cardiometabolic Risk Factors ◽  
Obese Women ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Age Related

ObjectiveTo investigate whether cardiometabolic factors were associated with age-related differences in cortical thickness in relation to sex.MethodsIn this cross-sectional study, we enrolled 1,322 cognitively normal elderly (≥65 years old) individuals (774 [58.5%] men, 548 [41.5%] women). We measured cortical thickness using a surface-based analysis. We analyzed the associations of cardiometabolic risk factors with cortical thickness using multivariate linear regression models after adjusting for possible confounders and interactions with age.ResultAmong women, hypertension (β = −1.119 to −0.024, p < 0.05) and diabetes mellitus (β = −0.920, p = 0.03) were independently associated with lower mean cortical thickness. In addition, there was an interaction effect between obesity (body mass index [BMI] ≥27.5 kg/m2) and age on cortical thickness in women (β = −0.324 to −0.010, p < 0.05), suggesting that age-related differences in cortical thickness were more prominent in obese women compared to women with normal weight. Moreover, low education level (<6 years) was correlated with lower mean cortical thickness (β = −0.053 to −0.046, p < 0.05). Conversely, among men, only being underweight (BMI ≤18.5 kg/m2, β = −2.656 to −0.073, p < 0.05) was associated with lower cortical thickness.ConclusionsOur findings suggest that cortical thickness is more vulnerable to cardiometabolic risk factors in women than in men. Therefore, sex-specific prevention strategies may be needed to protect against accelerated brain aging.

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