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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 4  |  Page : 151-155

Study on the role of inflammation in healthy aging and nutritional status in older persons


1 Department of Geriatric Medicine Madras Medical College; Professor of Medicine, ACS Medical College and Hospital, Chennai, Tamil Nadu, India
2 Associate Professor of Geriatric Medicine, Government Mohan Kumaramangalam Medical College, Salem, Tamil Nadu, India
3 Assistant Professor of Geriatric Medicine, Madras Medical College, Chennai, Tamil Nadu, India

Date of Submission17-Oct-2020
Date of Decision01-Dec-2020
Date of Acceptance09-Jan-2021
Date of Web Publication23-Feb-2021

Correspondence Address:
Dr. S Deepa
Associate Professor of Geriatric Medicine, Department of Geriatric Medicine, Government Mohan Kumaramangalam Medical College, Salem
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiag.jiag_14_20

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  Abstract 


Objective: The objective of this study is to assess the levels of inflammatory cytokines such as highly sensitive C-reactive protein (hsCRP) and interleukin (IL)-6 in healthy older persons compared to healthy younger persons. To determine the association between the nutritional status and levels of inflammatory markers in older persons. Methods: This is a single center, cross-sectional, analytical study, conducted in the Geriatric Unit of Rajiv Gandhi Government General Hospital, Madras Medical College, Chennai, India, during the period, February 2013–November 2013. Ninety healthy older persons aged 60 years and above and 90 healthy young adults aged 40 years and below were randomly selected to participate in this study. Blood samples were collected from the participants to analyze the hsCRP and IL-6 levels. Mini nutritional assessment was done in older participants to find out the nutritional status. Results: The older participants' mean age was 66.83 ± 6.1, and the mean age of the younger participants was 29.31 ± 7.4. The mean ± standard deviation of hsCRP level in healthy younger participants was 5.69 ± 3.21 and in healthy older participants was 6.05 ± 3.49. There was no significant difference in the level of inflammatory marker hsCRP between healthy younger and older participants (P = 0.476). The mean rank value of IL-6 in healthy younger participants was 84.45 and in healthy older participants was 96.55. There was no statistically significant difference in the levels of inflammatory marker IL-6 between healthy younger and older participants (P = 0.092). In this study, there was no statistically significant association between nutritional status and hsCRP (P = 0.156) and IL-6 (P = 0.286) levels in older people. Conclusion: The hsCRP and IL-6 levels were not significantly elevated in healthy older people than healthy younger adults in this study. There was no significant association between nutritional status and hsCRP and IL-6 levels in the older people in this study.

Keywords: Cytokines, high-sensitivity C-reactive protein, inflammaging, interleukin-6, mininutritional assessment, nutrition


How to cite this article:
Krishnaswamy B, Deepa S, Thangam D. Study on the role of inflammation in healthy aging and nutritional status in older persons. J Indian Acad Geriatr 2020;16:151-5

How to cite this URL:
Krishnaswamy B, Deepa S, Thangam D. Study on the role of inflammation in healthy aging and nutritional status in older persons. J Indian Acad Geriatr [serial online] 2020 [cited 2021 Apr 20];16:151-5. Available from: http://www.jiag.com/text.asp?2020/16/4/151/309998




  Introduction Top


A low grade, chronic, systemic upregulation of the inflammatory response which accompanies ageing is called inflammaging and these inflammatory changes are common to most age associated diseases. Inflammation is usually localized and self-limiting and does not produce any measurable systemic response. In severe infections and injuries, systemic activation of inflammation occurs, resulting in a measurable elevation in the acute-phase reactants and inflammatory cytokines. Aging is accompanied by a 2–4-fold increase in the inflammatory mediators and acute-phase reactants such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, highly sensitive C-reactive protein (hsCRP), and serum amyloid A.[1] Whatever the trigger may be, the final common pathway of inflammation occurs through the nuclear transcription factor, i.e., nuclear factor kappa B (NFκB). When activated, NFκB causes the expression of inflammatory mediators such as IL-6, IL-8, and monocyte chemoattractant protein-1. The increased levels of oxygen-free radicals, cytokine-secreting senescent cells, and adipocytes trigger the NFκB to produce more inflammatory mediators. Many age-associated chronic diseases also increase the levels of inflammatory markers in older persons. Many studies have shown a strong association between the levels of inflammatory markers and adverse health outcomes such as sarcopenia, frailty, disability, and death in older people.[2],[3]

Nutrition, health status, and clinical outcomes are interrelated. Many diseases have a detrimental effect on the older individual's ability to consume an adequate amount of nutrients. This is mostly seen in conditions that induce inflammatory response such as acute and chronic infections, chronic kidney disease, chronic obstructive pulmonary disease, congestive cardiac failure, malignancy, and inflammatory arthritis. It is a perceived concept that aging is associated with a dysregulated inflammatory response, as indicated by increased inflammatory cytokines. These cytokines produce signs and symptoms related to inflammation such as anorexia, weight loss, anemia, hypoalbuminemia, cachexia, and sarcopenia. Although anorexia is a contributing factor, fat and muscle loss induced by inflammation is refractory to nutritional support. Adequate nutritional supplementation will not reverse the inflammation-induced catabolism but slows the process of developing cachexia.[4] Most of the studies in humans mainly focused on the relationship between inflammation and appetite and food intake. The relationship between inflammation and nutritional status in older people has been rarely studied. Hence, we proposed a study to assess the levels of inflammatory cytokines such as hsCRP and IL-6 in healthy older persons compared to healthy younger persons and determine the association between the nutritional status and levels of inflammatory markers in older persons.


  Methods Top


This is a single center, cross-sectional, an analytical study in which we assessed the levels of inflammatory markers such as hsCRP and IL-6 in the healthy older persons compared to healthy younger persons. The present study was conducted from February 2013 to November 2013. The study was approved by the Institutional Ethical Committee of Madras Medical College, Chennai, India. We enrolled 120 older persons aged 60 and above and 110 younger adults aged 40 years and below who accompanied the Geriatric medicine outpatient department at Rajiv Gandhi Govt General Hospital, Chennai, India. Necessary information such as name, age, sex, address, and phone number was obtained from the enrolled. A detailed medical history, clinical examination, and investigations such as complete blood count, blood sugar and urea, serum creatinine, lipid profile, electrocardiogram, and a chest X-ray posteroanterior view were made in all the enrolled. Those with hypertension, diabetes, coronary artery disease, connective tissue disorders, acute and chronic infections and illnesses, and those who were on anti-inflammatory drugs were excluded from the study. One group of 90 healthy older persons aged 60 years and above and another group of 90 healthy young adults aged 40 and below were randomly selected from the enrolled persons to participate in the study. Written informed consent was obtained from all the study participants. The blood sample was collected from the participants to assess the levels of hsCRP and IL-6. hsCRP level was measured using immune turbidometry method, and IL6 level was measured using the enzyme-linked immunosorbent assay. The nutritional status of the older participants was assessed using mininutritional assessment (MNA). MNA is a validated tool in screening and evaluation of nutritional status in older people. It consists of 18 questions, and when the score is <17, the person is malnourished, if the score is 17–23.5, the person is at risk of developing malnutrition, and if it is 24–30 points, the person has normal nutritional status. It has a sensitivity of 96%, specificity of 98%, and a positive predictive value of 97%. MNA can detect the risk of malnutrition in older persons even when the albumin and body mass index (BMI) are in the normal range.[5]

Statistical analysis

Normality tests such as Kolmogorov–Smirnov and Shapiro–Wilks showed that the variables BMI and CRP followed normal distribution. Therefore, to compare the mean values between the groups, independent samples t-test was applied. To compare between BMI levels and MNA levels, one-way analysis of variance was applied. The variable IL6 does not follow normal distribution. Therefore, nonparametric tests were employed to analyze the data. To compare the mean values between the groups, the Mann–Whitney test was applied. To compare between BMI levels and MNA levels, Kruskal–Wallis test was applied. To compare the proportions between groups, the Chi-square test was applied. The analysis of the data was done using the IBM SPSS Statistics for Windows, Version 22.0, Armonk, NY: IBM Corp, Released in 2013. Significance level was fixed as 5% (α = 0.05).


  Results Top


Ninety healthy older persons and 90 healthy younger adults were randomly selected to participate in the study. Descriptive statistics (mean ± standard deviation or count/proportion) were calculated for each variable. The older participants' mean age was 66.83 ± 6.1, and the mean age of the younger participants was 29.31 ± 7.4. Fifty-three older participants and 58 younger participants were females. The younger participants have significantly higher BMI than the older participants (P = 0.004). The baseline characteristics of the study participants are tabulated in [Table 1].
Table 1: Baseline characteristics of the participants

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The levels of inflammatory markers such as hsCRP and IL-6 were measured in healthy older and younger persons – the mean ± standard deviation of hsCRP level in healthy younger participants was 5.69 ± 3.21 and in healthy older participants was 6.05 ± 3.49. There was no significant difference in the levels of inflammatory markers hsCRP between healthy younger and older participants (P = 0.476), as shown in [Table 2] and [Figure 1].
Table 2: Mean highly sensitive C-reactive protein levels between the study groups

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Figure 1: Mean value of high-sensitivity C-reactive protein between the study groups

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The variable IL-6 did not follow normal distribution. Therefore, nonparametric tests were employed to analyze the data. To compare the mean values between groups, the Mann–Whitney test was applied. There was no significant difference in the levels of IL-6 between healthy younger and older participants (P = 0.092), as shown in [Table 3] and [Figure 2].
Table 3: Mean rank of interleukin-6 levels between the study groups

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Figure 2: Mean rank value of interleukin-6 between the study groups

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We grouped older people according to the age as 60–64, 65–69, 70–74, 75–79, and 80 years and above. There was no significant association between the different age groups of older participants and levels of hsCRP (P = 0.216) and IL-6 (P = 0.435), as shown in [Table 4] and [Table 5].
Table 4: Mean highly sensitive C-reactive protein levels between age groups in older participants

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Table 5: Mean rank of interleukin-6 between age groups in older participants

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In the younger group, 32 were male, and 58 were female. In the older group, 37 were male, and 53 were female. In this study, there was no significant association between the levels of CRP and IL-6 and gender in both study groups, as shown in [Table 6] and [Table 7].
Table 6: Mean highly sensitive C-reactive protein levels among genders in both study groups

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Table 7: Mean rank of interleukin-6 levels among genders in both study groups

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BMI was calculated for the participants by the formula weight in kg divided by height in m2. The older participants were classified based on the Asian criteria as underweight (BMI <18.5), normal (BMI 18.5–22.9), overweight (BMI 23–24.9), and obese (BMI ≥25). There was no significant association between BMI and levels of hsCRP (P = 0.557) and IL-6 (P = 0.117) in the older participants, as shown in [Table 8] and [Table 9].
Table 8: Association between highly sensitive C-reactive protein levels and body mass index in older participants

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Table 9: Association between interleukin-6 levels and body mass index in older participants

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Nutritional assessment was done in older participants using MNA. Out of 90 older participants, 42 had normal nutritional status, 41 were at risk of developing malnutrition, and seven were malnourished. In this study, there was no significant association between nutritional status and hsCRP (P = 0.156) and IL-6 (P = 0.286) levels in the older people, as shown in [Table 10] and [Table 11].
Table 10: Association between highly sensitive C-reactive protein levels and mininutritional assessment in the older participants

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Table 11: Association between interleukin-6 levels and mininutritional assessment in the older participants

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  Discussion Top


This study, which included 90 healthy older persons and 90 healthy young adults, showed that the hsCRP and IL-6 levels were not significantly elevated in healthy older persons than healthy younger adults. The results of our study are consistent with the results of a few other studies.[6],[7] There was a lack of association between age and IL-6 levels in a study by Kim et al.[8] A study by Wyczalkowska-Tomasik et al analysed CRP and IL-6 levels in healthy individuals of various age groups, and found that the mean CRP and IL-6 levels in the 60-70 age group were significantly higher than that of the younger age group. They concluded in their study that healthy older people had serum levels of CRP and pro-inflammatory cytokines in the normal range, but higher than younger people, suggesting an adjustment of normal ranges in the elderly.[9] Other studies also showed an age-associated increase in the levels of inflammatory markers such as IL-6 and CRP.[10],[11] The reason for this variation in these studies is that older persons with diabetes and hypertension were included in the study, which might have altered the levels of inflammatory cytokines. Our study excluded persons with diabetes, hypertension, chronic diseases, infections, connective tissue disorders, and those on anti-inflammatory drugs that can alter the levels of inflammatory cytokines.

In this study, hsCRP and IL-6 levels were not significantly elevated between the genders in both study groups. This is in concordance with the study by Ferrucci et al.[11]

Aging is associated with an increase in total body fat and a loss in lean muscle mass. Central redistribution of fat causes increases in visceral adiposity. Adipose tissue by secreting adipokines plays an essential role in inflammation by increasing inflammatory cytokines such as IL-6 and TNF-α. Some studies have shown an association between the volume of subcutaneous adipose tissue and visceral adipose tissue with inflammatory markers such as CRP and IL-6. In these studies, to assess the volume of adipose tissue, multidetector computed tomography was used. These studies also suggested that the association of visceral fat volume to inflammation may not be accounted for by BMI and waist circumference.[12] In our study, there was no association between BMI and inflammatory markers such as IL-6 and hsCRP. Some longitudinal studies also showed that BMI ≥30 was a significant predictor of increased levels of IL-6 in the follow-up.[10] Our study was a cross-sectional study, and we measured only BMI, and we have not assessed the visceral adiposity.

Older people frequently have a poor appetite and inadequate dietary intake leading to increased risk of malnutrition.[4],[13] Studies have shown that a higher CRP level was associated with decreased appetite and food intake in patients on dialysis and in cancer patients.[14],[15],[16] IL-6 and TNF-α increases the circulating levels of leptin; an anorexigenic hormone leads to decreased appetite and food intake. Aging is associated with a state of persistently elevated pro-inflammatory cytokines. Pro-inflammatory cytokines cause catabolism of muscle proteins. Most of the studies in humans mainly focused on the relationship between inflammation and appetite and food intake. The relationship between inflammation and nutritional status in older people has rarely been studied. The purpose of this study is to determine if there is an association between inflammation and nutritional status in healthy older people. A study by Honda et al. showed that malnutrition was best predicted by hsCRP and IL-6 levels in end-stage renal disease patients.[17] A recent study by Fatyga et al. showed no significant difference in the levels of hsCRP and IL-6 in participants at risk of malnutrition and those with normal nutritional status.[18] A study by Bouillanne also revealed that CRP level was not significantly different in three classes of nutritional status.[19] In our study, there was no association between the levels of IL-6 and hsCRP and the older persons' nutritional status.

Limitations

The sample size of the study is small. The association between the inflammatory markers and nutritional status is not established in this study, since it is a cross-sectional study with few participants having malnutrition.


  Conclusion Top


In the study conducted among the healthy younger adults and healthy older persons, it was found that there was no significant difference in the levels of inflammatory markers such as IL-6 and hsCRP between the two groups. Further, it was found out that there was no association between the levels of inflammatory markers such as IL-6 and hsCRP and the nutritional state of the older participants. Inflammation, whether it has a role in the causation of diseases in the old or is merely a marker of underlying conditions, is yet to be concluded. More research needs to be done to prove a causal relationship between inflammation and aging and age-associated diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Wyczalkowska-Tomasik A, Czarkowska-Paczek B, Zielenkiewicz M, Paczek L. Inflammatory markers change with age, but do not fall beyond reported normal ranges. Arch Immunol Ther Exp (Warzs) 2016;64:249-54.  Back to cited text no. 9
    
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Zhu S, Patel KV, Bandinelli S, Ferrucci L, Guralnik JM. Predictors of interleukin-6 elevation in older adults. J Am Geriatr Soc 2009;57:1672-7.  Back to cited text no. 10
    
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Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood 2005;105:2294-9.  Back to cited text no. 11
    
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Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: The Framingham heart study. Circulation 2007;116:1234-41.  Back to cited text no. 12
    
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Van Der Pols-Vijlbrief R, Wijnhoven HA, Schaap LA, Terwee CB, Visser M. Determinants of protein-energy malnutrition in community-dwelling older adults: A systematic review of observational studies. Ageing Res Rev 2014;18:112-31.  Back to cited text no. 13
    
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Vannini FD, Antunes AA, Caramori JC, Martin LC, Barretti P. Associations between nutritional markers and inflammation in hemodialysis patients. Int Urol Nephrol 2009;41:1003-9.  Back to cited text no. 14
    
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Zabel R, Ash S, King N, Bauer J. The relationship between subjective appetite sensations, markers of inflammation and appetite in dialysis patients. J Hum Nutr Diet 2009;22:343-50.  Back to cited text no. 15
    
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Laird BJ, McMillan DC, Fayers P, Fearon K, Kaasa S, Fallon MT, et al. The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 2013;18:1050-5.  Back to cited text no. 16
    
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Honda H, Quereshi AR, Heimbürger O, Barany P, Wang K, Pecoits-Filho R, et al. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 2006;47:139-48.  Back to cited text no. 17
    
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Fatyga P, Pac A, Fedyk-Łukasik M, Grodzicki T, Skalska A. The relationship between malnutrition risk and inflammatory biomarkers in the outpatient geriatric population. Eur Geriatr Med 2020;11:383-91.  Back to cited text no. 18
    
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Bouillanne O, Golmard JL, Coussieu C, Noël M, Durand D, Piette F, et al. Leptin a new biological marker for evaluating malnutrition in elderly patients. Eur J Clin Nutr 2007;61:647-54.  Back to cited text no. 19
    


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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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