In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015-1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001). Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

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Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study

The present invention is directed to nanoparticulate compositions comprising megestrol. The megestrol particles of the composition have an effective average particle size of less than about 2000 nm.

Nanoparticulate megestrol formulations

/pdf/c-reactive-protein-levels-predict-the-incidence-of-delirium-15hfu1ydjx.pdf

C-reactive protein levels predict the incidence of delirium and recovery from it.

Background Inflammation plays a major role in both aging and chronic disease. Longitudinal studies in very old people can improve our understanding of these processes. We investigated blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and their combinations as predictors of mortality in nonagenarians. Methods This is a prospective population-based study including both community-dwelling and institutionalized nonagenarians enrolled in the Vitality 90+ Study. Altogether 285 persons participated in the baseline interview and gave blood. Information on chronic disease was drawn from health center registers. Data on mortality over 4 years were obtained from the Population Register Center. In Cox proportional hazards models, chronic disease and major risk factors were adjusted for. Results Plasma levels of IL-1ra, IL-6, and CRP were higher in persons who died during the follow-up than in those who survived. When sex, education, cardiovascular disease, diabetes, cancer, history of infections, high density lipoprotein cholesterol, Mini-Mental State Examination, body mass index, smoking status, and exercise were adjusted for, only IL-1ra was a significant predictor of mortality (hazard ratio [HR] 2.12; 95% confidence interval [CI], 1.24-3.62). Persons in the upper tertiles of both CRP and IL-1ra (HR 2.72; 95% CI, 1.25-6.00), or in the upper tertile of all three markers (HR 2.34; 95% CI, 1.23-4.61), had higher mortality than those who were not in the upper tertile in any of the markers. Conclusions IL-1ra is a powerful prognostic marker in very old people. Our results implicate its role in the complex interaction between inflammatory markers in aging and disease.

Interleukin-1 Receptor Antagonist, Interleukin-6, and C-Reactive Protein as Predictors of Mortality in Nonagenarians: The Vitality 90+ Study

BACKGROUND Recent studies have suggested that inflammation may play an important role in aging and the development of disabilities, but knowledge about its importance in the development of muscle weakness and functional disabilities in very old people is limited. This study examined associations between inflammatory markers and physical performance among nonagenarians. METHODS The population-based sample consisted of 197 women and 65 men aged 90 years. Physical performance was assessed according to the Barthel Index, the chair stand, and handgrip strength. Plasma levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and C-reactive protein (CRP) were determined. RESULTS A gender-adjusted linear regression model showed that high levels of CRP, IL-6, and IL-1Ra were significantly associated with poor handgrip strength (p = .041, p = .023, p < .001, respectively). After adjustment for diseases, smoking and physical exercise high levels of IL-6 and IL-1Ra were still significantly associated with poor hand grip strength (p = .048, p = .004, respectively). In the gender-adjusted model, high levels of CRP, IL-6, and IL-1Ra were significantly associated with a worse Barthel Index (p = .009, p = .004, p = .004, respectively). High levels of CRP and IL-6 were still significantly associated with a worse Barthel Index after adjusted for diseases, smoking and physical exercise (p = .034, p = .041, respectively). In the chair stand, no significant association with inflammatory markers was found. CONCLUSIONS Associations between high levels of inflammatory markers and worse handgrip strength as well as a worse Barthel Index result were evident among nonagenarians. However, the association with the chair stand was not significant.

/pdf/inflammatory-markers-and-physical-performance-among-1569ut4b0n.pdf

Inflammatory Markers and Physical Performance Among Nonagenarians

OBJECTIVES: To establish whether the relationship between interleukin-6 (IL-6) and plasma lipid and C-reactive protein (CRP) concentrations is different in Finnish nonagenarians than in middle-aged subjects with lower inflammatory status. DESIGN: Cross-sectional. SETTING: Observational cohort study concentrating on the oldest old. PARTICIPANTS: Nonagenarians (n = 291, mean age ± standard deviation 90 ± 1; 68 men, 223 women) who lived in the Tampere municipality in southern Finland and a middle-aged control population from the same area (n = 227, aged 44 ± 8). MEASUREMENTS: Plasma high sensitive CRP and lipid concentrations were analyzed using an automatic analyzer and IL-6 levels using enzyme-linked immunosorbent assay. RESULTS: Plasma concentrations of IL-6 (4.39 ± 5.25 vs 1.88 ± 1.98 pg/mL) and CRP (3.54 ± 4.98 vs 1.53 ± 1.91 mg/L) were significantly higher in nonagenarians than in middle-aged subjects (P<.001). In nonagenarians, plasma CRP levels increased (P<.001) and plasma total cholesterol (P=.006), low-density lipoprotein cholesterol (P=.02), and high-density lipoprotein cholesterol (P=.002) levels decreased according to IL-6 quartiles. In middle-aged subjects, similar associations were not found. CONCLUSION: The relationship between IL-6 and plasma CRP and cholesterol levels in nonagenarians with enhanced systemic inflammation differs from that of middle-aged subjects.

and Antti Hervonen Md

Papers

Interleukin-6 Modulates Plasma Cholesterol and C-Reactive Protein Concentrations in Nonagenarians