DOCSLIB.ORG

Deregulation of IL-37 and Its Mirnas Modulators in Sarcopenic Patients

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Deregulation of IL-37 and Its Mirnas Modulators in Sarcopenic Patients La Rosa et al. J Transl Med (2021) 19:172 https://doi.org/10.1186/s12967-021-02830-5 Journal of Translational Medicine RESEARCH Open Access Deregulation of IL-37 and its miRNAs modulators in sarcopenic patients after rehabilitation Francesca La Rosa1* , Simone Agostini1, Marina Saresella1, Andrea Saul Costa1, Federica Piancone1, Rossella Miglioli2, Fabio Trecate2 and Mario Clerici1,3 Abstract Background: sarcopenia is a highly prevalent condition in elderly individuals which is characterized by loss of mus- cle mass and functions; recent results showed that it is also associated with infammation. Rehabilitation protocols for sarcopenia are designed to improve physical conditions, but very scarce data are available on their efects on infam- mation We verifed whether in sarcopenic patients the infammation is reduced by rehabilitation and investigated the biological correlates of such efect. Methods: Twenty-one sarcopenic patients undergoing a specifcally-designed rehabilitation program were enrolled in the study. Physical, cognitive and nutritional parameters, as well as the concentration of C-Reactive Protein (CRP), pro-and anti-infammatory cytokines and cytokine production-modulating miRNAs were measured at the beginning (T0) and at end (30-days; T1) of the rehabilitation. Results: Rehabilitation resulted in a signifcant improvement of physical and cognitive conditions; this was accom- panied by a signifcant reduction of CRP (p 0.04) as well as of IL-18 (p 0.008) and IL-37 (p 0.009) concentration. Notably, the concentration of miR-335-3p (p= 0.007) and miR-657, the =two known post-transcriptional= regulators of IL-37 production, was increased by the rehabilitation= protocol. Conclusions: Results herein confrm that successful rehabilitation for sarcopenia results in a reduction of the infam- matory milieu, raise the possibility that IL-37 may be a key target to monitor the rehabilitation-associated improve- ment in sarcopenia, and suggest that this cytokine could be a therapeutic target in sarcopenic patients. Keywords: Cytokines, IL-37, Infammaging, MiRNAs, Rehabilitation, Sarcopenia Background People (EWGSOP) [5] developed defnitions, diagnostic Sarcopenia is a condition characterized by a progres- criteria, categories, and stages in sarcopenia and identi- sive decline of muscle mass, quality, and strength [1, 2]. fed sedentary life as one of the main predisposing factors Te prevalence of sarcopenia among people older than for age-related muscle loss [6–8]. Notably, sarcopenia is 65 years is estimated to be as high as 15%, and 50% of also associated with infammation [9] within the so called people over the age of 80 sufer from this condition [3, infammaging process: the preferential production of 4]. Te European Working Group on Sarcopenia in Older proinfammatory cytokines during aging, possibly as a consequence of an age-related redox imbalance that acti- vates pro-infammatory signaling pathways [10]. Infam- *Correspondence: [email protected] matory markers including interleukin 6 (IL-6), C Reactive 1 IRCCS Fondazione Don Carlo Gnocchi-ONLUS, Milano, Italy Full list of author information is available at the end of the article Protein (CRP) and tumor necrosis factor-alpha (TNF-a) © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. La Rosa et al. J Transl Med (2021) 19:172 Page 2 of 8 were shown to positively correlate with sarcopenia [11]. 30 days; during this period they underwent the following However, because several factors are known to afect rehabilitative treatment: twice daily session of 40′ in the the production of infammatory proteins, it is difcult morning and 30′ in the afternoon with assisted mobiliza- to understand their potential usefulness in the diagnosis tion, progressive muscle strengthening, associated with and the monitoring of sarcopenia is difcult. More-in- progressivity of the load, standing work proprioceptive depth analyses of vast panels of immune markers, thus, postural balance, walking training frstly with an assisted could help in the identifcation of new biomarkers for way and then without. sarcopenia. Physical activity, such as aerobic exercise For each subject, Short Physical Performance Battery training, remains the most import strategy to prevent (SPPB) [23], Barthel Index [24, 25], and the Tinetti Bal- age-related muscle decline [12–16], but the observation ance Test to predict falls among individuals [26–28] were that sarcopenia is associated with infammation raised calculated before and after treatment; anthropometric the possibility that interventions to reduce age-associate measurements including age, sex, weight (kg) and height muscular degeneration could target such process [17, 18]. (cm) were measured while patients were wearing light Infammation is an extremely complex process that clothes without shoes. Te study conformed to the ethi- involves a number of diferent proteins. Interleukin 37 cal principles of the Declaration of Helsinki; all subjects (IL-37), in particular, is a cytokine with anti-infamma- gave informed and written consent according to a pro- tory properties that was shown to play a critical role in tocol approved by the local ethics committee of the Don limiting excessive infammatory responses [19, 20]. In Carlo Gnocchi Foundation–ONLUS, Milan, Italy. humans, IL-37 production is not constitutive but is rather activated by pro-infammatory stimuli, including the Comprehensive geriatric assessment, nutrition status production of IL-1β, IL-18, TNF-α, IFN-γ, as a protec- function and social behavior tive mechanism to prevent excessive infammation and At baseline all the individuals enrolled in the study under- tissue damage [21]. As is the case with all genes, IL-37 went a comprehensive geriatric multidimensional evalu- expression is modulated by microRNAs (miRNAs), short ation that included cognitive function evaluation with non-coding RNAs (about 20–24 nucleotides) involved in Mini-Mental State Examination (MMSE) [29] and Clock mRNA silencing and post-transcriptional regulation via Drawing test (CDT) (score range 0–5) [30]. Emotional their ability to bind the 3′untranslated region (3′UTR). status was evaluated via the Yesavage Geriatric Depres- Data on miRNAs-mediated IL-37 regulation are scarce: sion Scale (Yesavage GDS) [31] and comorbidity was very recent results obtained in women with a diagnosis of evaluated with Charlson Comorbidity Index (CCI) [32]. gestational diabetes mellitus showed that miR-657 modu- Functional status was assessed using A.D.L. (activitiy of lates IL-37, infuencing the infammatory response [22]. daily living or KATZ index) (bathing, dressing, toilet- In silico analysis (see mirtarbase and genecards) indi- ing, transfer, feeding, continence) and I.A.D.L (Lawton- cated that miR-335-3p can modulate the IL-37 expres- Brody instrumental activity of daily living) (telephone sion as well. use, housekeeping, laundry, medication use, transporta- In this pilot work we analyzed whether rehabilitation tion, preparing meal, shopping, handling fnances) tests programs designed to improve function in sarcopenic [33–36]. Finally, Mini-Nutritional Assessment (MNA) patients would result in a reduction of infammation. was applied to all participants to analyze the nutritional Results indicating that rehabilitation-associated improve- status [37]. ment in the parameters used to monitor sarcopenia cor- related with a signifcant reduction of IL-37 led us to Whole blood and plasma sampling and processing investigate the post-transcription miRNA-mediated About thirty milliliters of whole blood were collected in mechanism involved in IL-37 production, including miR- EDTA-containing vacutainer tubes (Becton Dickinson 657 and miR-335-3p. and Co., Rutherford, NJ, USA). Peripheral blood mono- nuclear cells (PBMCs) were separated on lymphocyte Methods separation medium (Organon Teknika Corp., Durham, Participant recruitment NC, USA), and washed twice in PBS. Leukocytes viabil- Te study was conducted between January 2019 and ity was determined using a Bio-Rad TC20 Automated September 2019 at the Palazzolo Institute, Don Gnoc- Cell Counter (Bio-Rad, Hercules, CA, USA) and cryo- chi Foundation, Milan, Italy. Twenty-one patients were preserved at − 80 °C in RPMI 1640 containing 50% fetal recruited (13 Females and 8 Males). Patients were diag- bovine serum (FBS) and 10% dimethylsulfoxide (DMSO) nosed as being afected by severe sarcopenia according until using. to the European Working Group on Sarcopenia in Older Plasma was obtained from blood collected
Load more

Recommended publications
  • Brain Inflammaging: Roles of Melatonin, Circadian Clocks
    C al & ellu ic la n r li Im C m Journal of Clinical & Cellular f u o n l o a l n o Hardeland, J Clin Cell Immunol 2018, 9:1 r g u y o J Immunology DOI: 10.4172/2155-9899.1000543 ISSN: 2155-9899 Mini Review Open Access Brain Inflammaging: Roles of Melatonin, Circadian Clocks and Sirtuins Rüdiger Hardeland* Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany *Corresponding author: Rüdiger Hardeland, Johann Friedrich Blumenbach Institute of Zoology and Anthropology, Bürgerstrasse. 50, D-37073 Göttingen, Germany, Tel: +49-551-395414; E-mail: [email protected] Received date: February 13, 2018; Accepted date: February 26, 2018; Published date: February 28, 2018 Copyright: ©2018 Hardeland R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium. Abstract Inflammaging denotes the contribution of low-grade inflammation to aging and is of particular importance in the brain as it is relevant to development and progression of neurodegeneration and mental disorders resulting thereof. Several processes are involved, such as changes by immunosenescence, release of proinflammatory cytokines by DNA-damaged cells that have developed the senescence-associated secretory phenotype, microglia activation and astrogliosis because of neuronal overexcitation, brain insulin resistance, and increased levels of amyloid-β peptides and oligomers. Melatonin and sirtuin1, which are both part of the circadian oscillator system share neuroprotective and anti-inflammatory properties. In the course of aging, the functioning of the circadian system deteriorates and levels of melatonin and sirtuin1 progressively decline.
    [Show full text]
  • Cellular Senescence: Friend Or Foe to Respiratory Viral Infections?
    Early View Perspective Cellular Senescence: Friend or Foe to Respiratory Viral Infections? William J. Kelley, Rachel L. Zemans, Daniel R. Goldstein Please cite this article as: Kelley WJ, Zemans RL, Goldstein DR. Cellular Senescence: Friend or Foe to Respiratory Viral Infections?. Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.02708-2020). This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Copyright ©ERS 2020. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. Cellular Senescence: Friend or Foe to Respiratory Viral Infections? William J. Kelley1,2,3 , Rachel L. Zemans1,2 and Daniel R. Goldstein 1,2,3 1:Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA 2:Program in Immunology, University of Michigan, Ann Arbor, MI, USA 3:Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI USA Email of corresponding author: [email protected] Address of corresponding author: NCRC B020-209W 2800 Plymouth Road Ann Arbor, MI 48104, USA Word count: 2750 Take Home Senescence associates with fibrotic lung diseases. Emerging therapies to reduce senescence may treat chronic lung diseases, but the impact of senescence during acute respiratory viral infections is unclear and requires future investigation. Abstract Cellular senescence permanently arrests the replication of various cell types and contributes to age- associated diseases.
    [Show full text]
  • Age-Related Cerebral Small Vessel Disease and Inflammaging
    Li et al. Cell Death and Disease (2020) 11:932 https://doi.org/10.1038/s41419-020-03137-x Cell Death & Disease REVIEW ARTICLE Open Access Age-related cerebral small vessel disease and inflammaging Tiemei Li1,2,YinongHuang1,3,WeiCai1,2, Xiaodong Chen1,2, Xuejiao Men1,2, Tingting Lu1,2, Aiming Wu1,2 and Zhengqi Lu 1,2 Abstract The continued increase in global life expectancy predicts a rising prevalence of age-related cerebral small vessel diseases (CSVD), which requires a better understanding of the underlying molecular mechanisms. In recent years, the concept of “inflammaging” has attracted increasing attention. It refers to the chronic sterile low-grade inflammation in elderly organisms and is involved in the development of a variety of age-related chronic diseases. Inflammaging is a long-term result of chronic physiological stimulation of the immune system, and various cellular and molecular mechanisms (e.g., cellular senescence, immunosenescence, mitochondrial dysfunction, defective autophagy, metaflammation, gut microbiota dysbiosis) are involved. With the deepening understanding of the etiological basis of age-related CSVD, inflammaging is considered to play an important role in its occurrence and development. One of the most critical pathophysiological mechanisms of CSVD is endothelium dysfunction and subsequent blood-brain barrier (BBB) leakage, which gives a clue in the identification of the disease by detecting circulating biological markers of BBB disruption. The regional analysis showed blood markers of vascular inflammation are often associated with deep perforating arteriopathy (DPA), while blood markers of systemic inflammation appear to be associated with cerebral amyloid angiopathy (CAA). Here, we discuss recent findings in the pathophysiology of inflammaging and their effects on the development of age-related CSVD.
    [Show full text]
  • Retinal Inflammaging: Pathogenesis and Prevention
    Vol 4, Issue 4, 2016 ISSN - 2321-4406 Review Article RETINAL INFLAMMAGING: PATHOGENESIS AND PREVENTION ABHA PANDIT1, DEEPTI PANDEY BAHUGUNA2, ABHAY KUMAR PANDEY3*, PANDEY BL4, S Pandit5 1Department of Medicine, Index Medical College Hospital and Research Centre, Indore, Madhya Pradesh, India. 2Consultant, Otorhinolaryngologist, Shri Laxminarayan Marwari Multispeciality Charity Hospital, Varanasi, Uttar Pradesh, India. 3Department of Physiology, Government Medical College, Banda, Uttar Pradesh, India. 4Department of Pharmacology, IMS, Banaras Hindu University, Varanasi, Uttar Pradesh, India. 5Department of Ophthalmology, Health Services, Indore, Madhya Pradesh, India. Email: [email protected] Received: 09 June 2016, Revised and Accepted: 14 June 2016 ABSTRACT Macula lutea, the yellow spot or fovea centralis in eye, serves the distinctive central vision in perceiving visual cues and contributing to task performance. Impaired visual acuity, in later years in life, compromises safety, productivity, and life quality. Carotenoid pigment content declines with cumulation of light-induced damage through aging process in the retina. The progression of resultant macular degeneration is aggravated by oxidative stress, inflammation, raised blood sugar, and vasculopathy associating aging. Senescent dry degeneration involves drusen (a compound of glycolipid and glycol-conjugate core) deposition that impairs metabolic connectivity of upper layers of retina with choroid. Degeneration of retinal pigment epithelium and photoreceptors thus results. The late more severe form of age-related macular degeneration (AMD), involves factors inducing choroidal neovascularization. Leaky neocapillaries speed degenerative process of the retina. Most age-related pathologies are initiated by metabolic disruptions and AMD shares features of systemic atherosclerosis. An aberrant tissue response to free radical stress, vasculopathy, and local ischemic underlies AMD pathogenesis.
    [Show full text]
  • Cellular Senescence and Inflammaging in the Skin Microenvironment
    International Journal of Molecular Sciences Review Cellular Senescence and Inflammaging in the Skin Microenvironment Young In Lee 1,2 , Sooyeon Choi 1, Won Seok Roh 1 , Ju Hee Lee 1,2,* and Tae-Gyun Kim 1,* 1 Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 107-11, Korea; [email protected] (Y.I.L.); [email protected] (S.C.); [email protected] (W.S.R.) 2 Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Yonsei University College of Medicine, Seoul 107-11, Korea * Correspondence: [email protected] (J.H.L.); [email protected] (T.-G.K.); Tel.: +82-2-2228-2080 (J.H.L. & T.-G.K.) Abstract: Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called “inflammaging”. Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process. Keywords: inflammaging; senescence; skin; fibroblasts; keratinocytes; melanocytes; immune cells Citation: Lee, Y.I.; Choi, S.; Roh, W.S.; Lee, J.H.; Kim, T.-G. Cellular Senescence and Inflammaging in the 1.
    [Show full text]
  • Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging Rachel Thomas1, Weikan Wang1 and Dong-Ming Su2*
    Thomas et al. Immunity & Ageing (2020) 17:2 https://doi.org/10.1186/s12979-020-0173-8 REVIEW Open Access Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging Rachel Thomas1, Weikan Wang1 and Dong-Ming Su2* Abstract Immune system aging is characterized by the paradox of immunosenescence (insufficiency) and inflammaging (over-reaction), which incorporate two sides of the same coin, resulting in immune disorder. Immunosenescence refers to disruption in the structural architecture of immune organs and dysfunction in immune responses, resulting from both aged innate and adaptive immunity. Inflammaging, described as a chronic, sterile, systemic inflammatory condition associated with advanced age, is mainly attributed to somatic cellular senescence-associated secretory phenotype (SASP) and age-related autoimmune predisposition. However, the inability to reduce senescent somatic cells (SSCs), because of immunosenescence, exacerbates inflammaging. Age-related adaptive immune system deviations, particularly altered T cell function, are derived from age-related thymic atrophy or involution, a hallmark of thymic aging. Recently, there have been major developments in understanding how age-related thymic involution contributes to inflammaging and immunosenescence at the cellular and molecular levels, including genetic and epigenetic regulation, as well as developments of many potential rejuvenation strategies. Herein, we discuss the research progress uncovering how age-related thymic involution contributes to immunosenescence and inflammaging, as well as their intersection. We also describe how T cell adaptive immunity mediates inflammaging and plays a crucial role in the progression of age-related neurological and cardiovascular diseases, as well as cancer. We then briefly outline the underlying cellular and molecular mechanisms of age-related thymic involution, and finally summarize potential rejuvenation strategies to restore aged thymic function.
    [Show full text]
  • Reversing the Immune Ageing Clock: Lifestyle Modifications And
    Biogerontology (2018) 19:481–496 https://doi.org/10.1007/s10522-018-9771-7 (0123456789().,-volV)(0123456789().,-volV) REVIEW ARTICLE Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions Niharika A. Duggal Received: 27 June 2018 / Accepted: 16 September 2018 / Published online: 29 September 2018 Ó The Author(s) 2018 Abstract It is widely accepted that ageing is Immune ageing and health accompanied by remodelling of the immune system, including reduced numbers of naı¨ve T cells, increased Over the past 250 years life expectancy has increased senescent or exhausted T cells, compromise to mono- dramatically and is still increasing at 2 years per cyte, neutrophil and natural killer cell function and an decade in most countries. Advancing age is accompa- increase in systemic inflammation. In combination nied by a compromised ability of older adults to these changes result in increased risk of infection, combat bacterial and viral infections (Gavazzi and reduced immune memory, reduced immune tolerance Krause 2002; Molony et al. 2017a, b), increased risk of and immune surveillance, with significant impacts autoimmunity (Goronzy and Weyand 2012), poor upon health in old age. More recently it has become vaccination responses (Del Giudice et al. 2017; Lord clear that the rate of decline in the immune system is 2013) and the re-emergence of latent infections to malleable and can be influenced by environmental produce conditions such as shingles (Schmader 2001). factors such as physical activity as well as pharmaco- All of this contributing towards increased morbidity logical interventions. This review discusses briefly our and mortality in older adults (Pera et al.
    [Show full text]
  • Cellular Senescence and the Senescent Secretory Phenotype: Therapeutic Opportunities
    Cellular senescence and the senescent secretory phenotype: therapeutic opportunities Tamara Tchkonia, … , Judith Campisi, James L. Kirkland J Clin Invest. 2013;123(3):966-972. https://doi.org/10.1172/JCI64098. Review Series Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions. Find the latest version: https://jci.me/64098/pdf Review series Cellular senescence and the senescent secretory phenotype: therapeutic opportunities Tamara Tchkonia,1 Yi Zhu,1 Jan van Deursen,1 Judith Campisi,2 and James L. Kirkland1 1Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA. 2Buck Institute for Research on Aging, Novato, California, USA. Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mech- anism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP).
    [Show full text]
  • Inflammaging in the Intervertebral Disc
    Article Clinical & Translational Neuroscience January–June 2018: 1–9 ª The Author(s) 2018 Inflammaging in the intervertebral disc Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2514183X18761146 journals.sagepub.com/home/ctn Aleksandra Sadowska1 , Oliver Nic Hausmann2, and Karin Wuertz-Kozak1,3,4,5 Abstract Degeneration of the intervertebral disc – triggered by ageing, mechanical stress, traumatic injury, infection, inflammation and other factors – has a significant role in the development of low back pain. Back pain not only has a high prevalence, but also a major socio-economic impact. With the ageing population, its occurrence and costs are expected to grow even more in the future. Disc degeneration is characterized by matrix breakdown, loss in proteoglycans and thus water content, disc height loss and an increase in inflammatory molecules. The accumulation of cytokines, such as interleukin (IL)-1 , IL-8 or tumor necrosis factor (TNF)- , together with age-related immune deficiency, leads to the so-called inflammaging – low-grade, chronic inflammation with a crucial role in pain development. Despite the relevance of these molecular processes, current therapies target symptoms, but not underlying causes. This review describes the biological and biomechanical changes that occur in a degenerated disc, discusses the connection between disc degen- eration and inflammaging, highlights factors that enhance the inflammatory processes in disc pathologies and suggests future research avenues. Keywords Intervertebral
    [Show full text]
  • The Role of Cytokines in Extreme Longevity
    Arch. Immunol. Ther. Exp. DOI 10.1007/s00005-015-0377-3 REVIEW Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity 1 2 3 Paola Lucia Minciullo • Antonino Catalano • Giuseppe Mandraffino • 1 2 4 2 Marco Casciaro • Andrea Crucitti • Giuseppe Maltese • Nunziata Morabito • 2 1 2 Antonino Lasco • Sebastiano Gangemi • Giorgio Basile Received: 16 June 2015 / Accepted: 2 November 2015 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2015 Abstract Longevity and aging are two sides of the same as mediators of cytokines. We believe that if inflammaging is coin, as they both derive from the interaction between a key to understand aging, anti-inflammaging may be one of genetic and environmental factors. Aging is a complex, the secrets of longevity. dynamic biological process characterized by continuous remodeling. One of the most recent theories on aging focuses Keywords Inflammaging Á Anti-inflammaging Á on immune response, and takes into consideration the acti- Cytokine Á Aging Á Longevity vation of subclinical, chronic low-grade inflammation which occurs with aging, named ‘‘inflammaging’’. Long-lived Abbreviations people, especially centenarians, seem to cope with chronic IL Interleukin subclinical inflammation through an anti-inflammatory NK Natural killer cells response, called therefore ‘‘anti-inflammaging’’. In the pre- TNF Tumor necrosis factor sent review, we have focused our attention on the contrast IFN Interferon between inflammaging and anti-inflammaging systems, by IL-18BP IL-18 binding protein evaluating the role of cytokines and their impact on extreme SNPs Single nucleotide polymorphisms longevity. Cytokines are the expression of a network IL-1Ra IL-1 receptor antagonist involving genes, polymorphisms and environment, and are Hsp Heat shock proteins involved both in inflammation and anti-inflammation.
    [Show full text]
  • Ageing Research Reviews Inflammaging As a Common Ground
    Ageing Research Reviews 56 (2019) 100980 Contents lists available at ScienceDirect Ageing Research Reviews journal homepage: www.elsevier.com/locate/arr Review Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis T Gregory Livshitsa,b,*, Alexander Kalinkovicha a Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel. b Adelson School of Medicine, Ariel University, Ariel, Israel. ARTICLE INFO ABSTRACT Keywords: Sarcopenia, obesity and their coexistence, obese sarcopenia (OBSP) as well as atherosclerosis-related cardio- Inflammaging vascular diseases (ACVDs), including chronic heart failure (CHF), are among the greatest public health concerns Obesity in the ageing population. A clear age-dependent increased prevalence of sarcopenia and OBSP has been regis- Sarcopenia tered in CHF patients, suggesting mechanistic relationships. Development of OBSP could be mediated by a Atherosclerosis crosstalk between the visceral and subcutaneous adipose tissue (AT) and the skeletal muscle under conditions of Cardiomyopathy low-grade local and systemic inflammation, inflammaging. The present review summarizes the emerging data Dysbiosis supporting the idea that inflammaging may serve as a mutual mechanism governing the development of sar- copenia, OBSP and ACVDs. In support of this hypothesis, various immune cells release pro-inflammatory mediators in the skeletal muscle and myocardium. Subsequently, the endothelial structure is disrupted, and cellular processes, such as mitochondrial activity, mitophagy, and autophagy are impaired. Inflamed myocytes lose their contractile properties, which is characteristic of sarcopenia and CHF. Inflammation may increase the risk of ACVD events in a hyperlipidemia-independent manner. Significant reduction of ACVD event rates, without the lowering of plasma lipids, following a specific targeting of key pro-inflammatory cytokines confirms a key role of inflammation in ACVD pathogenesis.
    [Show full text]
  • Inflammaging, Metabolic Syndrome and Melatonin: a Call for Treatment Studies
    Cardinali, Daniel P. ; Hardeland, Rüdiger Inflammaging, metabolic syndrome and melatonin: a call for treatment studies Preprint del documento publicado en Neuroendocrinology Vol. 104, N° 4, 2017 Este documento está disponible en la Biblioteca Digital de la Universidad Católica Argentina, repositorio institucional desarrollado por la Biblioteca Central “San Benito Abad”. Su objetivo es difundir y preservar la producción intelectual de la Institución. La Biblioteca posee la autorización de los autores y de la editorial para su divulgación en línea. Cómo citar el documento: Cardinali DP, Hardeland R. Inflammaging, metabolic syndrome and melatonin : a call for treatment studies [en línea]. Preprint del documento publicado en Neuroendocrinology 2017;104(4):982-392. doi: 10.1159/000446543. Disponible en: http://bibliotecadigital.uca.edu.ar/repositorio/investigacion/inflammaging-metabolic-syndrome-melatonin.pdf [Fecha de consulta: ….] Publicado en Neuroendocrinology 104(4):382-397; 2017 Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies Daniel P. Cardinali a, Rüdiger Hardeland b a BIOMED-UCA-CONICET and Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina b Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Berliner Str. 28, D-37073 Goettingen, Germany Running title: Melatonin and the Metabolic Syndrome Key Words: Melatonin – Metabolic syndrome – Inflammation – Diabetes – Obesity - Insulin signaling
    [Show full text]