Overweight and obesity, to a greater degree, are conditions characterized by abnormal or excessive fat accumulation that impair health and bring about psychosocial and economic difficulties. They are considered risk factors for a number of diseases, such as cardiovascular, musculoskeletal, type 2 diabetes mellitus, and some types of cancers [1, 2]. In 2016, more than one-third of adults worldwide were classified as obese or overweight, both in developed and developing countries. Of note, most of the world’s population lives in countries where overweight and obesity kill more people than being underweight [3].

The world’s population is also aging increasingly over the years. Globally, the population aged 60 or over is growing faster than all younger age groups, and it is expected that the number of older persons will double by 2050 and more than triple by 2100 [4]. Aging, often called senescence, is a natural process characterized by a gradual decline in body functions due to multiple organ dysfunctions. Collectively, these data indicate that the combination of excessive weight and aging may confer greater risks of diseases and death.

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Figure1: Excessive weight and aging are associated with marked changes in the immune system, leading to a state of chronic low-grade inflammation considered risk factors for a number of diseases, such as cardiovascular, musculoskeletal, type 2 diabetes mellitus, and some types of cancers. CXCL16 (chemokine CXCL16), BMP-2 (bone morphogenetic protein), IL-17 (interleukin-17). Figure courtesy Luiz O C Rodrigues.

The immune system is considered the most protective system of the body, as it keeps the organisms free of invaders, either internal or external. It regulates the inflammatory response, a reaction of cells/tissues after infection or injury, which is characterized by redness, heat, swelling, pain, and loss of function [5]. The immune system is intrinsically connected with other systems, such as the endocrine (composed by glands that produce hormones that regulate the metabolism, growth, and development) and neurological (a complex network of cells and messengers that record and distribute information from the brain and spinal cord to various part of the body) systems.

Therefore, immune dysfunctions have great potential to be deleterious [6]. Both excessive weight and aging are associated with marked changes in the immune system, leading to a state of chronic low-grade inflammation [7, 8]. Obese, overweight, and old individuals are more susceptible to viral, bacterial, and fungal infections [1]. The links between excessive adipose (fat) tissue accumulation and aging, along with the observation that adults with excessive weight are prematurely aged individuals, led the field researchers to postulate the term “adipaging” [9].

Cytokines are bioactive molecules produced by many different cells (e.g. in the blood and adipose tissue) that coordinate local and systemic inflammatory responses and other biological processes. As their levels are altered in different inflammatory diseases, there is enormous clinical interest in the quantification of cytokines in body samples like blood and urine as biological markers, or “biomarkers,” of disease severity, progression, or response to treatments. Obesity/overweight and senescence share alterations in the body levels of several cytokines [10]. Despite extensive research over the past decades, our understanding of the role of cytokines in obesity/overweight and aging remains limited.

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Considering the promising use of cytokines as biomarkers of chronic diseases associated with excessive weight and senescence and the link between these processes, we investigated the levels of three soluble cytokines in the blood (interleukine-17/IL-17, chemokine CXCL-16, and the bone morphogenetic protein-2/BMP-2) in middle-aged women and elderly women with overweight and obesity. We correlated these data with anthropometric parameters of the studied women, which assess the size, shape, and proportions of the human body. This study was published in the Immunity & Ageing journal in 2017 [11].

According to our data, the blood levels of CXCL-16, IL-17, and BMP-2 were higher in all obese and most of the overweight women when compared to normal weight women, independently of age. Obese women tended to have increased levels of these cytokines than overweight women. However, we observed that the focus of medical attention must start with overweight individuals because, in terms of the production of inflammatory mediators, they are very similar to the obese ones. In other words, we cannot neglect the overweight because this condition is “in an inflammatory speaking” similar to that condition (obesity) associated with different comorbidities. In our society, sometimes being overweight is partially accepted and living among us using an invisible mask. When produced in excess, CXCL-16 and IL-17 might contribute to the development of atherosclerosis, a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls that lead to cardiovascular diseases [12, 13].

BMP-2 is a potent inducer of bone formation, but it is also associated with various adverse events when in excess, for example, induction of inflammation [14]. Therefore, the overproduction of these cytokines might predispose the development of chronic diseases in the future. In addition, these cytokines were correlated in a positive manner with anthropometric parameters, especially in the elderly. This means that women who have increased CXCL-6, IL-17, and BMP-2 levels also have higher body measurements associated with fat accumulation in this period of life. It is worth noting that obese and overweight women in middle age had similar levels of IL-17 and BMP-2 as elderly women with normal weight, suggesting that having excessive weight in adult life resembles these cytokines’ profiles in senescence.

The present study provides complementary information about IL-17, CXCL-16, and BMP-2, and their potential as soluble biomarkers related to excessive weight in middle-aged and elderly women. However, they need to be further investigated by population studies that follow overweight and obese individuals as they get older. These studies will confirm if cytokines, like those measured in our study, could be useful in the preventive management of chronic inflammatory diseases associated with excessive weight and aging.

These findings are described in the article entitled CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women, recently published in the journal Immunity & Ageing.

References:

  1. Frasca D, McElhaney J. Influence of Obesity on Pneumococcus Infection Risk in the Elderly. Front Endocrinol (Lausanne). 2019;10:71. doi: 10.3389/fendo.2019.00071. PubMed PMID: 30814978; PubMed Central PMCID: PMCPMC6381016.
  2. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253. PubMed PMID: 11234459; eng.
  3. Ralston J, Brinsden H, Buse K, et al. Time for a new obesity narrative. Lancet. 2018 Oct 20;392(10156):1384-1386. doi: 10.1016/S0140-6736(18)32537-6. PubMed PMID: 30316458.
  4. United Nations DoEaSA, Population Division World Population Prospects: The 2017 Revision, Key Findings and Advance Tables 2017. Available from: https://esa.un.org/unpd/wpp/Publications/Files/WPP2017_KeyFindings.pdf
  5. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008 Jul;454(7203):428-35. doi: 10.1038/nature07201. PubMed PMID: 18650913; eng.
  6. Homo-Delarche F, Dardenne M. The neuroendocrine-immune axis. Springer Semin Immunopathol. 1993;14(3):221-38. PubMed PMID: 8094904.
  7. Xia S, Zhang X, Zheng S, et al. An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment. J Immunol Res. 2016;2016:8426874. doi: 10.1155/2016/8426874. PubMed PMID: 27493973; PubMed Central PMCID: PMCPMC4963991.
  8. Masoodi M, Kuda O, Rossmeisl M, et al. Lipid signaling in adipose tissue: Connecting inflammation & metabolism. Biochim Biophys Acta. 2014 Oct. doi: 10.1016/j.bbalip.2014.09.023. PubMed PMID: 25311170; Eng.
  9. Perez LM, Pareja-Galeano H, Sanchis-Gomar F, et al. ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J Physiol. 2016 Jun 15;594(12):3187-207. doi: 10.1113/JP271691. PubMed PMID: 26926488; PubMed Central PMCID: PMCPMC4908019.
  10. Tchkonia T, Morbeck DE, Von Zglinicki T, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010 Oct;9(5):667-84. doi: 10.1111/j.1474-9726.2010.00608.x. PubMed PMID: 20701600; PubMed Central PMCID: PMCPMC2941545.
  11. Ribeiro S, Lopes LR, Paula Costa G, et al. CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women. Immun Ageing. 2017;14:6. doi: 10.1186/s12979-017-0089-0. PubMed PMID: 28293269; PubMed Central PMCID: PMCPMC5346187.
  12. Lu X. The Impact of IL-17 in Atherosclerosis. Curr Med Chem. 2017;24(21):2345-2358. doi: 10.2174/0929867324666170419150614. PubMed PMID: 28425862.
  13. Sheikine Y, Sirsjo A. CXCL16/SR-PSOX–a friend or a foe in atherosclerosis? Atherosclerosis. 2008 Apr;197(2):487-95. doi: 10.1016/j.atherosclerosis.2007.11.034. PubMed PMID: 18191863.
  14. Nguyen V, Meyers CA, Yan N, et al. BMP-2-induced bone formation and neural inflammation. J Orthop. 2017 Jun;14(2):252-256. doi: 10.1016/j.jor.2017.03.003. PubMed PMID: 28367006; PubMed Central PMCID: PMCPMC5362134.

About The Author

Adjunct Professor, Department of Clinical Nutrition, Federal University of Ouro Preto, MG, Brazil.

Graduate in Nutrition, Adjunct Professor of the Clinical Nutrition Department of the Federal University of Ouro Preto and researcher at the Laboratory of Immunobiology of Inflammation (http://sites.ufop.br/labiin). Area of action: metabolic disorders (in particular, obesity) and inflammatory response.

Graduated in Pharmacy, laboratory technician in Genomics and professor of Clinical Microbiology. Universidade Federal de Ouro Preto (UFOP), MG, Brazil.

Luiza O. Perucci works as a laboratory technician in the Laboratory of Genomics of the Nucleus of Research on Biological Sciences and as a substitute teacher in Pharmacy School, both atUFOP. Luiza is also a member of the Laboratory of the Immunology of Inflammation (http://sites.ufop.br/labiin) and collaborates with research projects at Faculty of Pharmacy at the Federal University of Minas Gerais, MG, Brazil. She develops research concerning the inflammatory response in human diseases, mainly in preeclampsia.

Federal University of Minas Gerais (MD, Ph.D.) Brazil

Clinical Coordinator of the Neurofibromatosis Outpatient Reference Center where he develops research concerning clinical aspects of these genetic diseases (see www.amanf.org.br). Professional cartoonist.

Graduated in Physical Education and Associate Professor of Sports TrainingFederal University of Ouro Preto (UFOP), MG, Brazil.

Kelerson MC Pinto is an adjunct professor at the UFOP Sports Center and coordinates theLaboratory of Immunobiology of Inflammation (http://sites.ufop.br/labiin) and is also a member of the Laboratory of Physiology of Exercise, Biomechanics, and Performance-CEDUFOP. Kelerson develops research on the inflammatory response mainly in the area of physical activity.

Immunologist and associate professor of parasitology
Federal University of Ouro Preto (UFOP), MG, Brazil.

André Talvani (orcid.org/0000-0002-6685-6229) is an associate professor and director of the Institute of the Exact and Biological Sciences at UFOP. Prof. Talvani is a CNPq research productivity fellows and coordinates the laboratory of the immunobiology of inflammation (http://sites.ufop.br/labiin) where develops research concerning the inflammatory response in the respective backgrounds (i) parasite infection and chemotherapy, (ii) respiratory disturbances, (iii) metabolic/nutritional disorders, (iv) physical activity and (v) phototherapy.