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1.  Total and Abdominal Adiposity Are Associated With Inflammation in Older Adults Using a Factor Analysis Approach 
Background.
Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. However, it is unclear if a specific combination of markers reflects the underlying inflammatory state. We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability.
Methods.
Adiponectin, CRP, IL-1ra, IL-1sRII, IL-2sRα, IL-6, IL-6sR, IL-8, IL-15, sTNFRI, sTNFRII, and TNF-α were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry.
Results.
IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP, IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not factor 1, was positively associated with 1-SD increments in waist circumference (β = 0.160 ± 0.057, p = .005), body mass index (β = 0.132 ± 0.053, p = .01), and total fat mass (β = 0.126 ± 0.053, p = .02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass. There were no significant interactions between adiposity and muscle mass or strength for either factor.
Conclusions.
Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population.
doi:10.1093/gerona/gls077
PMCID: PMC3437966  PMID: 22451470
Aging; Adiposity; Inflammation; Muscle impairment; Factor analysis
2.  Effect of exercise training on chronic inflammation 
Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.
doi:10.1016/j.cca.2010.02.069
PMCID: PMC3629815  PMID: 20188719
inflammation; exercise; cytokines; acute phase proteins; physical activity
3.  Caloric Restriction, Aerobic Exercise Training, and Soluble Lectin-like Oxidized LDL Receptor-1 Levels in Overweight and Obese Postmenopausal Women 
Background
Elevated circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) have been observed in obese persons and are reduced by weight loss. However, it is not known if combining caloric restriction (CR) with exercise training is better in reducing sLOX-1 levels than CR alone.
Objective
We examined whether the addition of aerobic exercise to a weight loss intervention differentially affects sLOX-1 levels in 61 abdominally obese postmenopausal women randomly assigned to a CR only (n=22), CR + moderate-intensity exercise (n=22), or CR + vigorous-intensity exercise (n=17) intervention for 20 weeks. The caloric deficit was ~2,800 kcal/week for all groups.
Results
The intervention groups were similar at baseline with respect to body weight, body composition, lipids, and blood pressure. However, plasma sLOX-1 levels were higher in the CR only group (99.90 ± 8.23 pg/ml) compared to both the CR + moderate-intensity exercise (69.39 ± 8.23 pg/ml, p=0.01) and CR + vigorous-intensity exercise (72.83 ± 9.36 pg/ml, p=0.03) groups. All three interventions significantly reduced body weight (~14%), body fat, and waist and hip circumferences to a similar degree. These changes were accompanied by a 23% reduction in sLOX-1 levels overall (−19.00 ± 30.08 pg/ml, p<0.0001), which did not differ among intervention groups (p=0.13). Changes in body weight, body fat, and VO2 max were not correlated with changes in sLOX-1 levels. In multiple regression analyses in all women combined, baseline sLOX-1 levels (β = − 0.70 ± 0.06, p<0.0001), age (β = 0.92 ± 0.43, p=0.03) and baseline BMI (β = 1.88 ± 0.66, p=0.006) were independent predictors of the change in sLOX-1 with weight loss.
Conclusions
Weight loss interventions of equal energy deficit have similar effects on sLOX-1 levels in overweight and obese postmenopausal women, with the addition of aerobic exercise having no added benefit when performed in conjunction with CR.
doi:10.1038/ijo.2010.199
PMCID: PMC3023845  PMID: 20856256
obesity; weight loss; caloric restriction; aerobic exercise; soluble receptor
4.  Exercise Training as a Treatment for Chronic Inflammation in the Elderly 
Persistent, sub-clinical inflammation predisposes to chronic disease, as well as the development of sarcopenia and disability, in frail elderly. Thus, the inflammatory pathway is a potential target for interventions to reduce aging-related disease and disability. This article highlights emerging data suggesting that increasing physical activity could be effective for reducing chronic inflammation in the elderly.
doi:10.1097/JES.0b013e3181b7b3d9
PMCID: PMC2789351  PMID: 19955865
aging; sarcopenia; inflammation; cytokines; physical activity
5.  Plasma Oxidized Low-density Lipoprotein Levels and Arterial Stiffness in Older Adults: the Health ABC Study 
Hypertension  2009;53(5):846-852.
Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease (CVD). Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2,295 participants (mean age, 74 yrs; 52% female; 40% black) from the Health, Aging and Body Composition study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1, 869 ± 376 cm/s; tertile 2, 901 ± 394 cm/s; tertile 3, 938 ± 415 cm/s; p=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional CVD risk factors (p=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, anti-hypertensive and antilipemic medications, and CRP the association with ox-LDL was attenuated, but remained significant (p=0.01). Results were similar when ox-LDL was expressed in absolute (mg/dL) or relative amounts (percent of LDL). Moreover, individuals in the highest ox-LDL tertile were 30-55% more likely to have high arterial stiffness, defined as aPWV > 75th percentile (p≤0.02). In conclusion, we found that among elderly persons, elevated plasma ox-LDL levels are associated with higher arterial stiffness, independent of CVD risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness.
doi:10.1161/HYPERTENSIONAHA.108.127043
PMCID: PMC2692957  PMID: 19332658
aging; epidemiology; aortic stiffness; pulse wave velocity; oxidative stress
6.  Chronic Inflammation Is Associated With Low Physical Function in Older Adults Across Multiple Comorbidities 
Background
Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status.
Methods
We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP); and anthropometric measures.
Results
Higher levels of CRP and IL-6, but not TNF-α, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results.
Conclusions
Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.
doi:10.1093/gerona/gln038
PMCID: PMC2657165  PMID: 19196644
Inflammation; Physical function; Aging; Comorbidities

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