Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Circulating Inflammatory Markers in Older Men

Abstract Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, is an important risk factor for morbidity and mortality in the aging population. It has been suggested that circadian disruption may play a role in chronic inflammation, but there has been limited study that investigated the overall profile of 24-hour rest-activity rhythms in relation to inflammation using longitudinal data. In the Outcomes of Sleep Disorders in Older Men Study, we applied the extended cosine model to derive multiple rest-activity rhythm characteristics using multi-day actigraphy, and examined their associations with six inflammatory markers (i.e., CRP, IL-6, TNF-α, TNF-α-sRII, IL-1 β, IFN-γ) measured from fasting blood. We assessed both the cross-sectional association between rest-activity rhythms and inflammatory markers measured at baseline, and the prospective association between baseline rest-activity rhythms and changes in in inflammatory markers over 3.5 years of follow up. We found that multiple rest-activity characteristics, including lower amplitude and relative amplitude, and decreased overall rhythmicity, were associated with higher levels of CRP, IL-6, TNF-α, and TNF-α-sRII, but not IL-1β and IFN-γ at baseline. Moreover, the lowest quartile of these three rest-activity characteristics was associated with an approximately two-fold increase in the odds of having elevated inflammation (i.e. having three or more markers in the highest quartile) at baseline. However, we found little evidence supporting a relationship between rest-activity rhythm characteristics and changes in inflammatory markers. Future studies should clarify the dynamic relationship between rest-activity rhythms and inflammation in different populations, and evaluate the effects of improving rest-activity profiles on inflammation and related disease outcomes.

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CROSS-SECTIONAL AND LONGITUDINAL RELATIONSHIPS BETWEEN REST-ACTIVITY RHYTHMS AND INFLAMMATION IN OLDER MEN

Innovation in Aging ◽

10.1093/geroni/igz038.1497 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S403-S403

Author(s):

Xiao Qian ◽

Qian Xiao ◽

Daniel S Evans ◽

Susan Redline ◽

Nancy Lane ◽

...

Keyword(s):

Sleep Disturbances ◽

Activity Rhythm ◽

Fold Increase ◽

Older Men ◽

Cross Sectional ◽

Sleep Study ◽

Activity Rhythms ◽

Lower Amplitude ◽

The Cross ◽

Rest Activity

Abstract Sleep disturbances and physical inactivity have been associated with chronic inflammation, an important risk factor for cognitive decline in the aging population. However most previous studies focused on the cross-sectional relationships between sleep and physical activity and inflammation. In the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study, we studied both the cross-sectional and prospective associations between characteristics of 24-hour rest-activity rhythms measured by actigraphy and inflammation index measured by multiple circulating markers. In cross-sectional analysis, a lower amplitude is associated with elevated inflammation (Odds ratio Q4 vs Q1 (95% Confidence interval): 1.65 (1.22, 2.24)). In prospective analysis, an earlier acrophase (<12:30) is associated with a two-fold increase in the risk of developing elevated inflammation over four years of follow up (2.08 (1.02, 4.23)). No individual inflammatory markers are associated with rest-activity rhythms. Our findings suggest that rest-activity rhythm characteristics predicts elevated inflammation.

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Cross-sectional and longitudinal relationships between rest-activity rhythms and circulating inflammatory markers in older men: the osteoporotic fractures in men sleep study

Sleep Medicine ◽

10.1016/j.sleep.2019.11.1178 ◽

2019 ◽

Vol 64 ◽

pp. S424-S425

Author(s):

Q. Xiao ◽

D. Evans ◽

S. Redline ◽

N. Lane ◽

S. Ancoli-Israel ◽

...

Keyword(s):

Inflammatory Markers ◽

Osteoporotic Fractures ◽

Older Men ◽

Cross Sectional ◽

Sleep Study ◽

Activity Rhythms ◽

Longitudinal Relationships ◽

Circulating Inflammatory Markers ◽

Rest Activity

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Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Metabolic Markers and Type 2 Diabetes in Older Men

10.2337/figshare.12816059 ◽

2020 ◽

Author(s):

Qian Xiao ◽

Jingyi Qian ◽

Daniel S Evans ◽

Susan Redline ◽

Nancy E. Lane ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fasting Glucose ◽

Activity Rhythm ◽

Older Men ◽

Cross Sectional ◽

Activity Rhythms ◽

The Cross ◽

Rest Activity

<a>OBJECTIVE Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes (T2D), yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.</a> RESEARCH DESIGN AND METHODS Baseline rest-activity rhythms were derived from actigraphy using extended cosine model analysis. Fasting glucose, insulin and <a>homeostasis model assessment of insulin resistance </a>(HOMA-IR) were measured from fasting blood at baseline and after ~3.5 years. T2D were defined using self-report, medication use and fasting glucose. RESULTS In the cross-sectional analysis (n=2,450), lower 24-hour amplitude:mesor ratio (i.e., mean-activity-adjusted rhythm amplitude) and reduced overall rhythmicity, were associated with higher fasting insulin and HOMA-IR (all p-trend < 0.0001), indicating increased insulin resistance. The odds of baseline T2D were significantly higher among those in the lowest quintile of amplitude (OR Q1 vs Q4 (95% CI), 1.63 (1.14, 2.30)) and late acrophase group (OR late vs normal (95% CI), 1.46 (1.04, 2.04)). In the prospective analysis (n=861), multiple rest-activity characteristics predicted a 2-3 fold increase in T2D risk, including a lower amplitude (OR Q1 vs Q4 (95% CI), 3.81 (1.45, 10.00)) and amplitude:mesor ratio (2.79 (1.10, 7.07), reduced overall rhythmicity (3.49 (1.34, 9.10)), and a late acrophase (2.44 (1.09, 5.47)). CONCLUSIONS Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident T2D.

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Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Metabolic Markers and Type 2 Diabetes in Older Men

10.2337/figshare.12816059.v1 ◽

2020 ◽

Author(s):

Qian Xiao ◽

Jingyi Qian ◽

Daniel S Evans ◽

Susan Redline ◽

Nancy E. Lane ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fasting Glucose ◽

Activity Rhythm ◽

Older Men ◽

Cross Sectional ◽

Activity Rhythms ◽

The Cross ◽

Rest Activity

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0286 Cross-Sectional and Longitudinal Relationships between Rest-Activity Rhythms and Metabolic Biomarkers in Older Men: The Osteoporotic Fractures in Men Sleep Study

SLEEP ◽

10.1093/sleep/zsz067.285 ◽

2019 ◽

Vol 42 (Supplement_1) ◽

pp. A116-A117

Author(s):

Qian Xiao ◽

Daniel S Evans ◽

Susan Redline ◽

Nancy Lane ◽

Sonia Ancoli-Israel ◽

...

Keyword(s):

Osteoporotic Fractures ◽

Older Men ◽

Cross Sectional ◽

Sleep Study ◽

Activity Rhythms ◽

Metabolic Biomarkers ◽

Longitudinal Relationships ◽

Rest Activity

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Blunted rest–activity rhythms link to higher body mass index and inflammatory markers in children

SLEEP ◽

10.1093/sleep/zsaa256 ◽

2020 ◽

Author(s):

Jingyi Qian ◽

Nuria Martinez-Lozano ◽

Asta Tvarijonaviciute ◽

Rafael Rios ◽

Frank A J L Scheer ◽

...

Keyword(s):

Sleep Duration ◽

Inflammatory Markers ◽

Activity Rhythm ◽

Activity Level ◽

Relative Amplitude ◽

Early Age ◽

Z Score ◽

Activity Rhythms ◽

Daytime Activity ◽

Rest Activity

Abstract Study Objectives Disturbances of rest–activity rhythms are associated with higher body mass index (BMI) in adults. Whether such relationship exists in children is unclear. We aimed to examine cross-sectional associations of rest–activity rhythm characteristics with BMI z-score and obesity-related inflammatory markers in school-age children. Methods Participants included 411 healthy children (mean ± SD age 10.1 ± 1.3 years, 50.8% girls) from a Mediterranean area of Spain who wore wrist accelerometers for 7 consecutive days. Metrics of rest–activity rhythm were derived using both parametric and nonparametric approaches. Obesity-related inflammatory markers were measured in saliva (n = 121). Results In a multivariable-adjusted model, higher BMI z-score is associated with less robust 24-h rest–activity rhythms as represented by lower relative amplitude (–0.16 [95% CI –0.29, –0.02] per SD, p = 0.02). The association between BMI z-score and relative amplitude persisted with additional adjustment for sleep duration, and attenuated after adjustment for daytime activity level. Less robust rest–activity rhythms were related to increased levels of several salivary pro-inflammatory markers, including C-reactive protein, which is inversely associated with relative amplitude (–32.6% [–47.8%, –12.9%] per SD), independently of BMI z-score, sleep duration, and daytime activity level. Conclusion Blunted rest–activity rhythms are associated with higher BMI z-score and salivary pro-inflammatory markers already at an early age. The association with BMI z-score seem to be independent of sleep duration, and those with pro-inflammatory markers further independent of BMI z-score and daytime activity. Novel intervention targets at an early age based on improving the strength of rest–activity rhythms may help to prevent childhood obesity and related inflammation. Clinical Trials Registration NCT02895282

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Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Metabolic Markers and Type 2 Diabetes in Older Men

Diabetes Care ◽

10.2337/dc20-0557 ◽

2020 ◽

Vol 43 (11) ◽

pp. 2702-2712

Author(s):

Qian Xiao ◽

Jingyi Qian ◽

Daniel S. Evans ◽

Susan Redline ◽

Nancy E. Lane ◽

...

Keyword(s):

Type 2 Diabetes ◽

Older Men ◽

Cross Sectional ◽

Metabolic Markers ◽

Activity Rhythms ◽

Rest Activity

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The combined effects of obesity and ageing on skeletal muscle function and tendon properties in vivo in men

Endocrine ◽

10.1007/s12020-020-02601-0 ◽

2021 ◽

Author(s):

David J. Tomlinson ◽

Robert M. Erskine ◽

Christopher I. Morse ◽

Joseph M. Pappachan ◽

Emmanuel Sanderson-Gillard ◽

...

Keyword(s):

Body Mass ◽

Older Men ◽

Normal Weight ◽

Skeletal Muscle Function ◽

Cross Sectional ◽

Tendon Stiffness ◽

Tnf Α ◽

Combined Impact ◽

Negative Relationships

Abstract Purpose We investigated the combined impact of ageing and obesity on Achilles tendon (AT) properties in vivo in men, utilizing three classification methods of obesity. Method Forty healthy, untrained men were categorised by age (young (18–49 years); older (50–80 years)), body mass index (BMI; normal weight (≥18.5–<25); overweight (≥25–<30); obese (≥30)), body fat% (normal adipose (<28%); high adiposity (≥28%)) and fat mass index (FMI; normal (3–6); excess fat (>6–9); high fat (>9). Assessment of body composition used dual-energy X-ray absorptiometry, gastrocnemius medialis (GM)/AT properties used dynamometry and ultrasonography and endocrine profiling used multiplex luminometry. Results Older men had lower total range of motion (ROM; −11%; P = 0.020), GM AT force (−29%; P < 0.001), stiffness (−18%; P = 0.041), Young’s modulus (−22%; P = 0.011) and AT stress (−28%; P < 0.001). All three methods of classifying obesity revealed obesity to be associated with lower total ROM (P = 0.014–0.039). AT cross sectional area (CSA) was larger with higher BMI (P = 0.030). However, after controlling for age, higher BMI only tended to be associated with greater tendon stiffness (P = 0.074). Interestingly, both AT CSA and stiffness were positively correlated with body mass (r = 0.644 and r = 0.520) and BMI (r = 0.541 and r = 0.493) in the young but not older adults. Finally, negative relationships were observed between AT CSA and pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Conclusions This is the first study to provide evidence of positive adaptations in tendon stiffness and size in vivo resulting from increased mass and BMI in young but not older men, irrespective of obesity classification.

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The association between rest-activity rhythms and glycemic markers: the US National Health and Nutrition Examination Survey, 2011-2014

SLEEP ◽

10.1093/sleep/zsab291 ◽

2021 ◽

Author(s):

Qian Xiao ◽

Charles E Matthews ◽

Mary Playdon ◽

Cici Bauer

Keyword(s):

National Health ◽

Multinomial Logistic Regression ◽

Oral Glucose ◽

Model Assessment ◽

Nutrition Examination Survey ◽

Activity Rhythms ◽

Health And Nutrition ◽

Lower Amplitude ◽

Glycemic Markers ◽

Rest Activity

Abstract OBJECTIVES Previous studies conducted in mostly homogeneous sociodemographic samples have reported a relationship between weakened and/or disrupted rest-activity patterns and metabolic dysfunction. This study aims to examine rest-activity rhythm characteristics in relation to glycemic markers in a large nationally-representative and diverse sample of American adults. METHODS This study used data from the National Health and Nutrition Examination Survey 2011-2014. Rest-activity characteristics were derived from extended cosine models using 24-hour actigraphy. We used multinomial logistic regression and multiple linear regression models to assess the associations with multiple glycemic markers (i.e., glycated hemoglobin, fasting glucose and insulin, homeostatic model assessment of insulin resistance, and results from the oral glucose tolerance test), and compared the results across different categories of age, gender, race/ethnicity and body-mass index. RESULTS We found that compared to those in the highest quintile of F statistic , a model-fitness measure with higher values indicating a stronger cosine-like pattern of daily activity, participants in the lowest quintile (i.e, those with the weakest rhythmicity) were 2.37 times more likely to be diabetic (OR Q1 vs. Q5 2.37 (95% CI 1.72, 3.26), p-trend <.0001). Similar patterns were observed for other rest-activity characteristics, including lower amplitude (2.44 (1.60, 3.72)), mesor (1.39 (1.01, 1.91)), and amplitude:mesor ratio (2.09 (1.46, 2.99)), and delayed acrophase (1.46 (1.07, 2.00)). Results were consistent for multiple glycemic biomarkers, and across different sociodemographic and BMI groups. CONCLUSIONS Our findings support an association between weakened and/or disrupted rest-activity rhythms and impaired glycemic control among a diverse US population.

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Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study

Acta Endocrinologica ◽

10.1530/eje-07-0038 ◽

2007 ◽

Vol 157 (4) ◽

pp. 419-426 ◽

Cited By ~ 10

Author(s):

David H St-Pierre ◽

Jean-Philippe Bastard ◽

Lise Coderre ◽

Martin Brochu ◽

Antony D Karelis ◽

...

Keyword(s):

Postmenopausal Women ◽

Inflammatory Markers ◽

Area Under The Curve ◽

Blood Lipid ◽

Cross Sectional Study ◽

Acylated Ghrelin ◽

Euglycemic Hyperinsulinemic Clamp ◽

Cross Sectional ◽

Tnf Α ◽

Maximal Reduction

Objective: Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and soluble TNF receptor 1 (sTNF-R1). Design: Cross-sectional study consisting of 50 overweight and obese postmenopausal women. Methods: AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-α, and sTNF-R1. Results: In fasting conditions, sTNF-R1 was negatively correlated with AcylG (r = −0.48, P < 0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (r = −0.44, P = 0.002) and positively with TNF-α (r = 0.38, P = 0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (r = −0.35, P = 0.02 and r = −0.34, P = 0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (r = −0.29, P < 0.05) and positively with TNF-α (r = 0.36, P = 0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-α. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG. Conclusion: These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-α system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity.

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