Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study.

We hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the “proinflammatory state” in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.

Background. Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people. The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population. Methods. This study is part of the “Invecchiare in Chianti” (InCHIANTI) study, a prospective population-based study of older people, aimed at identifying risk factors for late-life disability. The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy. Physical performance was assessed using walking speed, the chair-stand test, and the standing balance test. Hand-grip strength was assessed using a hand-held dynamometer. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), IL-10, IL-1β, IL-6sR, and IL-1RA were determined. Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance, scored as a continuous variable from 0 to 3, and hand-grip strength after adjustment for demographics, chronic conditions, medication use, and other biological variables. Results. CRP, IL-6, and IL1RA were significantly correlated with physical performance (r = −0.162, r = −0.251, and r = −0.127, respectively). Significant correlations with hand-grip strength were found for CRP and IL-6 (r = −0.081 and r = −0.089, respectively). After adjustment for covariates, high levels of IL-6 and IL-1RA continued to be strongly associated with worse physical performance ( p <.001 and p = 0.004, respectively). High levels of CRP ( p <.001) and IL-6 ( p <.001) were associated with low hand-grip strength. Mean adjusted physical performance scores ranged from 2.21 in the CRP < 0.59 mg/dl group to 2.07 in the CRP > 0.60 mg/dl group ( p for trend =.004), and from 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile ( p for trend <.001). This trend was also reflected in mean adjusted hand-grip strength, with a range from 28.8 kg for the CRP < 0.59 mg/dl group to 26.0 kg for the CRP > 0.60 mg/dl group ( p for trend =.001), and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile ( p for trend =.001). Conclusions. Inflammation, measured as high levels of IL-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons. These data also support the biological face validity of physical performance measures. The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention.

Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established. In 1123 persons (aged 20-98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGFbeta. Lower alpha-linolenic acid was associated with higher C-reactive protein and IL-1ra, and lower eicosapentaenoic acid was associated with higher IL-6 and lower TGFbeta. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P = 0.005), IL-1ra (P = 0.004), and TNFalpha (P = 0.040) and higher soluble IL-6r (P < 0.001), IL-10 (P = 0.024), and TGFbeta (P = 0.0012). Lower n-6 fatty acid levels were significantly associated with higher IL-1ra (P = 0.026) and lower TGFbeta (P = 0.014). The n-6 to n-3 ratio was a strong, negative correlate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates. In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNFalpha, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL-6r, IL-10, TGFbeta) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation.

The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as “sarcopenic obesity” (Roubenoff R. Ann NY Acad Sci 904: 553–557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index ≥30 kg/m². After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor ( P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity.

Aims The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. Methods and results We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of persons aged 65–95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) were measured. Complete information on potential confounders was collected using standard methods. WBC (P=0.0001), neutrophils (P<0.0001), C-reactive protein (P<0.0001), IL-1ra (P<0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18 (P<0.0001), TNF-α (P=0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P=0.004) and IL-6 (P=<0.0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and TNF-α, whereas non-significant trends were observed for WBC (P=0.1) and sIL-6r (P=0.2). Conclusion A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintiles.