Cytokines In Older Adults Research Articles

Objectively measured prolonged sleep is associated with plasma cytokines in older adults with mild cognitive impairment.

This study aimed to determine whether objective sleep time is associated with the concentrations of various plasma cytokines in older adults with mild cognitive impairment (MCI). In total, 118 adults with MCI (66 women; mean age: 75.7 years) participated in this prospective cohort study. All participants were required to wear a wristband sensor for 7.8 days, on average, every 3 months for 1 year and undergo measurement of 27 plasma cytokines using multiplex immunoassays. After adjusting for potential confounders, the associations of total sleep time with cytokine concentrations were assessed by multiple linear regression analysis. The total sleep time was significantly correlated with plasma interleukin (IL)-9 and macrophage inflammatory protein (MIP)-1β levels (r = 0.239, p = 0.009, and r = 0.242, p = 0.008, respectively). Moreover, these associations remained significant after adjusting for covariates, including demographic characteristics, lifestyle-related diseases, and apolipoprotein E status (β = 0.272, 95% confidence interval: 0.095-0.448, p = 0.003, and β = 0.27, 95% confidence interval: 0.092-0.449, p = 0.003, respectively). Thus, this study is the first to demonstrate the association between objective prolonged sleep and higher plasma IL-9 and MIP-1β levels in older adults with MCI.

The Impact of Behavioral Lifestyle Intervention on Inflammatory Cytokines in Older Adults Living With Type 2 Diabetes: A Feasibility Study.

This study investigates the effects of a behavioral lifestyle intervention on inflammatory cytokines and frailty in older adults (≥ 65 years) with type 2 diabetes (T2D). We conducted a single-arm, 6-month intervention supplemented with diet and activity self-monitoring technology. We assessed frailty using Fried criteria and quantified inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating-factor [GM-CSF], interferon [IFN-γ], tumor necrosis factor [TNF-α]) using a multiplex assay. We used paired t-tests with significance at P < .05. We calculated the Spearman correlation and evaluated the relationship between frailty, BMI, and inflammatory cytokines. Eighteen participants completed the study (mean ± SD: 71.5 ± 5.3 years; BMI: 34 ± 6 kg/m2). At baseline, we had 4 frail, 13 pre-frail, and 1 non-frail participant. At 6 months, we observed the therapeutic effects of the intervention on frailty score, BMI, IL-2, IFN-y, and GM-CSF. The study highlights the importance of behavioral lifestyle intervention in improving inflammatory cytokines and frailty in older adults.

Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.

Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.

Meals That Differ in Nutrient Composition and Inflammatory Potential Do Not Differentially Impact Postprandial Circulating Cytokines in Older Adults above a Healthy Weight.

In this exploratory study, mixed meals specifically formulated to differ in inflammatory potential were tested to determine whether they could differentially impact circulating levels of inflammatory markers in adults above a healthy weight. Complete data were analyzed from 11 adults (6 males and 5 females) aged 54–63 years with median BMI of 30.0 (27.1–31.6) kg/m². In a crossover study design, each participant consumed an isocaloric (2.2 MJ) meal with either a low (Anti-meal), moderate (Neutr-meal), or high (Pro-meal) inflammatory potential. Fasting and postprandial blood samples were analyzed for plasma levels of IL-6, IL-1β, TNF-α, IL-10, and metabolic makers. Postprandial plasma IL-6, IL-1β, TNF-α, and IL-10 incremental areas under the curve (iAUC) were not different between the three meals (p > 0.05). There was a trend of an increase in IL-6 with time in all three meals, but no changes were obvious for the other measured cytokines. The Pro-meal induced an increased postprandial iAUC for triglycerides compared to the Anti-meal and Neutr-meal (p = 0.004 and p = 0.012, respectively). Single meals, regardless of their theoretical inflammatory potential, did not substantially shift circulating inflammatory markers, suggesting that longer-term dietary patterns are important rather than single dietary exposures in the pathology of metabolic conditions.

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

Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, are 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 multiday actigraphy, and examined their associations with 6 inflammatory markers (ie, C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α], tumor necrosis factor alpha soluble receptor II [TNF-α-sRII], interleukin-1β [IL-1β], interferon gamma [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 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 3 rest-activity characteristics was associated with an approximately 2-fold increase in the odds of having elevated inflammation (ie, having 3 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.

Classical and lectin complement pathways and markers of inflammation for investigation of susceptibility to infections among healthy older adults

BackgroundThere is increasing recognition of the significance of chronic, low-level inflammation in older adults, or “inflammaging.” Innate immune responses and host-bacterial interactions are recognized as key factors in inflammaging. Inflammatory cytokine IL-6, and complement protein C1q have been identified as biomarkers for the development of frailty and aging-related diseases. Older adults are also susceptible to infections with serotypes of Streptococcus pneumoniae that bind ficolin-2, a component of the lectin complement pathway, and low ficolin-2 levels could possibly be involved in such susceptibility.MethodsThe aim of our study was to evaluate complement pathway components and biomarkers for inflammaging among older adults in order to investigate potential innate immune mechanisms that may account for susceptibility to infections in this population. We compared inflammatory markers, as well as components/activity of the classical and lectin complement pathways between healthy older and younger adults. We hypothesized that older adults would have higher levels of inflammatory markers and C1q, and lower levels of lectin pathway components. Older (≥70 years old) and younger (19–54 years old) adults without significant smoking history or chronic medical conditions were eligible for participation. Inflammatory markers (IL-6, TNF-α, CRP), classical complement pathway activity (CH50) and protein levels (C1q, C3, C4), and lectin pathway (MBL levels/activity, CL-L1, MASP-1/2/3, MAp44, MAp19, and H/M/L-ficolin) were compared between groups.ResultsOlder adults had significantly higher mean levels of IL-6 and TNF-α. There were no significant differences in lectin pathway components between older and younger adults. Unexpectedly, mean C1q was significantly higher in the younger group in both unadjusted and adjusted analyses. There was also a significant association between race and C1q levels, but this association did not completely account for the observed differences between age groups.ConclusionsWe did not observe deficiencies in lectin pathway components to account for increased susceptibility to ficolin-binding serotypes of S. pneumoniae. Elevated levels of inflammatory cytokines in older adults are suggestive of inflammaging. However, the observed age and race-associated changes in C1q have not been previously reported in the populations included in our study. These findings are relevant to the investigation of C1q in aging-related pathology, and for its proposed role as a biomarker for frailty and disease.

Using sweat to measure cytokines in older adults compared to younger adults: A pilot study

Background/objectivesCurrent measures of cytokines involve urine, blood or saliva which have drawbacks including circadian rhythm variations and complicated collection methods. Sweat has been used to measure cytokines in young and middle-aged adults, but not older adults. We sought to determine the feasibility of using sweat to measure cytokines in older adults compared to younger adults. DesignTwo visit cross-sectional pilot study stratified by age group. SettingIndependent living facility and Johns Hopkins University both in Maryland. Participants23 community-dwelling adults aged 65 and older and 26 adults aged 18–40 were included. Those with active cancer treatment or with a known terminal illness diagnosis were excluded. MeasurementsSweat interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) were collected using a non-invasive sweat patch worn for 72h by each participant. Samples were measured with a single molecule array (SIMOA) technology for ultrasensitive, multiplexed detection of proteins. Results23 older adults and 26 younger adults with mean ages of 77±8.0years and 28±5.5years, respectively, completed the study. Both groups had high rates of compliance with patch wearing and removal. Higher concentrations of TNF-α, IL-6 and IL-10 were observed in older adults compared to younger adults, which remained significant after controlling for race, sex, body mass index, and chronic disease count (0.110±0.030 vs. 0.054±0.020pg/mL, 0.089±0.012 vs. 0.048±0.018pg/mL, and 0.124±0.029 vs. 0.067±0.025pg/mL, respectively). ConclusionThese results suggest that sweat patches are a feasible method to collect cytokine data from older adults. Preliminary group differences in cytokine measurement between older and younger groups correspond with current literature that cytokines increase with age, suggesting that sweat measurement using the sweat patch provides a new method of exploring the impact of inflammation on aging. Further research using sweat and the sweat patch is recommended.

Load-Specific Inflammation Mediating Effects of Resistance Training in Older Persons

BackgroundLittle is known about the effects of resistance training (RT) on circulating cytokines in older adults. Also, dose-response relationships remain unclear. This study investigated the impact of RT at different external loads on circulating inflammatory mediators in older community-dwelling individuals. MethodsFifty-six community-dwelling older (68 ± 5 years) volunteers were randomized to 12 weeks of supervised RT (×3/week) at either high-resistance training [8 males, 10 females, 2 × 10–15 repetitions at 80% 1 repetition maximum (RM)], low-resistance training (9 males, 10 females, 1 × 80–100 repetitions at 20% 1 RM), or mixed low-resistance training (9 males, 10 females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10–20 repetitions at 40% 1 RM). Serum was available from 51 out of 56 participants at baseline and after 12 weeks for determination of interleukin (IL)-6, IL-8, IL-10, IL-1β, soluble tumor necrosis factor receptor (sTNFR)1, granulocyte macrophage colony-stimulating factor, and IL-1 receptor antagonist (ra). ResultsTwelve weeks of RT significantly increased sTNFR1 from 2.48 ± 0.57 ng/mL to 2.58 ± 0.59 ng/mL (overall time-effect P = .033) and Log IL-8 from 0.38 ± 0.18 pg/mL to 0.53 ± 0.32 pg/mL (overall time-effect P = .007). No time X group interaction (P = .916) was observed. In males of the high-resistance training group, there was an increase in Log IL-8 (from 0.45 ± 0.16 pg/mL to 0.68 ± 0.19 pg/mL; P = .005) and IL-1ra (from 68.60 ± 24.12 pg/mL to 79.56 ± 29.07 pg/mL; P = .007). No significant changes were found for the other markers. ConclusionsOur results show that 12 weeks of supervised RT induced an overall significant increase of circulating IL-8 and sTNFR1, independently from the external load applied. We suggest that exercising until volitional fatigue is the main trigger for exercise-induced responses. However, training at high external load also increased anti-inflammatory IL-1ra in male participants, which might be beneficial in combating low-grade inflammation.

Relation of Plasma Leptin to C-Reactive Protein in Older Adults (from the Invecchiare nel Chianti Study)

Obese subjects have higher circulating levels of C-reactive protein (CRP) than normal subjects, and it has been shown that CRP per se may contribute to atherogenesis. The mechanism linking increased fat mass with high CRP levels has not been exhaustively explained. It has been suggested that adipose tissue-produced cytokines, including interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta, represent the causal link between increased body fat and high CRP levels. It has been hypothesized that the hormone leptin, released by fat cells, may stimulate CRP production independent of cytokines. This study measured circulating leptin, CRP, interleukin-6, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 in 946 community-dwelling older subjects (398 men, 548 women; age range 65 to 102 years) enrolled in a large population-based study. Confounders included demographics, functional, cognitive and affective status, diet and lifestyle, body composition, drugs, and chronic diseases. A direct association was found between leptin and CRP (p = 0.004), independent of cytokines and other possible confounders. The association was stronger in younger than in older subjects but was not influenced by gender or body mass index. In conclusion, these findings suggest that leptin may directly stimulate the production of CRP independent of fat-cell produced cytokines in older adults.

Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults.

To address the long-term physiological consequences of chronic stressors, 14 continuing or current family caregivers of Alzheimer's disease (AD) patients, 17 former AD caregivers, and 31 control subjects were compared. Continuing and former caregivers did not differ on depressive symptomatology or perceived stress; both groups were significantly more depressed and stressed than controls. Furthermore, continuing and former caregivers did not differ in the response of NK cells in vitro to recombinant interferon-gamma and recombinant interleukin-2, and both groups had a significantly poorer response to these cytokines than controls. The physiological and psychological consequences of chronic stressors may persist well beyond the cessation of the actual stressor.

Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults.

To address the long-term physiological consequences of chronic stressors, 14 continuing or current family caregivers of Alzheimer's disease (AD) patients, 17 former AD caregivers, and 31 control subjects were compared. Continuing and former caregivers did not differ on depressive symptomatology or perceived stress; both groups were significantly more depressed and stressed than controls. Furthermore, continuing and former caregivers did not differ in the response of NK cells in vitro to recombinant interferon-gamma and recombinant interleukin-2, and both groups had a significantly poorer response to these cytokines than controls. The physiological and psychological consequences of chronic stressors may persist well beyond the cessation of the actual stressor.