{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:09Z","timestamp":1787028249689,"version":"build-2736575974"},"reference-count":126,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T00:00:00Z","timestamp":1484611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Geriatrics"],"abstract":"<jats:p>The clinical, pathological and biological characteristics of frailty and sarcopenia are becoming better understood and defined, including the role of systemic inflammation. It is increasingly apparent that in older adults there is a tendency for the innate immune network to shift toward a pro-inflammatory setting, often due to the presence of chronic inflammatory diseases but also associated with age alone in some individuals. Furthermore, acute inflammation tends to resolve more slowly and less completely in many elderly people. Inflammation contributes to the pathogenesis of sarcopenia and other components of the frailty syndrome. Blood levels of inflammatory cytokines and acute phase proteins, are reduced by exercise, and there is a growing body of epidemiological, observational and intervention research that indicates that regular moderate exercise improves strength, function, morbidity and mortality in middle-aged and elderly adults. There is also an increasing awareness of the potential role of drugs to ameliorate inflammation in the context of frail old age, which might be particularly useful for people who are unable to take part in exercise programs, or as adjunctive treatment for those who can. Drugs that shift the innate immune biochemical network toward an anti-inflammatory setting, such as methyl-xanthines and 4-amino quinolones, could be of value. For example, theophylline has been shown to induce a 20 percent fall in pro-inflammatory tumor necrosis factor (TNF) and 180 percent rise in anti-inflammatory interleukin-10 production by peripheral blood monocytes, and a fall of 45 percent in interferon-gamma (IF-gamma) release. Such properties could be of therapeutic benefit, particularly to re-establish a less inflamed baseline after acute episodes such as sepsis and trauma.<\/jats:p>","DOI":"10.3390\/geriatrics2010006","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T10:00:47Z","timestamp":1484733647000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Systemic Inflammation in the Genesis of Frailty and Sarcopenia: An Overview of the Preventative and Therapeutic Role of Exercise and the Potential for Drug Treatments"],"prefix":"10.3390","volume":"2","author":[{"given":"Stephen","family":"Allen","sequence":"first","affiliation":[{"name":"The Royal Bournemouth Hospital, Castle Lane East, Bournemouth, Dorset BH7 7DW, UK"},{"name":"Centre for Postgraduate Medical Education and Research, Bournemouth University, Bournemouth, Dorset BH12 5BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"ref_1","unstructured":"Definition of Frailty Syndrome. Available online: www.medicinenet.com\/script\/main\/art.asp?articlekey=26356."},{"key":"ref_2","unstructured":"BGS Guideline Fit for Frailty. Available online: www.bgs.org.uk\/index.php\/fit-for-frailty."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: Evidence for a phenotype","volume":"58","author":"Fried","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1471-2318-8-24","article-title":"A standard procedure for creating a frailty index","volume":"8","author":"Searle","year":"2008","journal-title":"BMC Geriatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/ageing\/afw148","article-title":"Sarcopenia, frailty and mortality: The evidence is growing","volume":"45","author":"Dodds","year":"2016","journal-title":"Age Ageing"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/ageing\/afq034","article-title":"Sarcopenia: European consensus on definition and diagnosis\u2014Report of the European working group on sarcopenia in older people","volume":"39","author":"Baeyens","year":"2010","journal-title":"Age Ageing"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.clnu.2009.12.004","article-title":"Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by special interest groups (SIG) \u201ccachexia-anorexia in chronic wasting diseases\u201d and \u201cnutrition in geriatrics\u201d","volume":"29","author":"Muscaritoli","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jamda.2011.01.003","article-title":"Sarcopenia: An undiagnosed condition in older adults\u2014Current consensus definition: Prevalence, etiology and consequences","volume":"12","author":"Fielding","year":"2011","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jamda.2011.04.014","article-title":"Sarcopenia with limited mobility: An international consensus","volume":"12","author":"Morley","year":"2011","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_10","first-page":"74","article-title":"The role of nutrition in frailty: An overview","volume":"5","author":"Goisser","year":"2016","journal-title":"J. Frailty Aging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bmb\/ldq008","article-title":"Sarcopenia: Characteristics, mechanisms and functional significance","volume":"95","author":"Narici","year":"2010","journal-title":"Br. Med. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0022-510X(88)90132-3","article-title":"What is the cause of ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus medialis muscle from 15\u201383-year-old men","volume":"84","author":"Lexell","year":"1988","journal-title":"J. Neurol. Sci"},{"key":"ref_13","first-page":"8798","article-title":"NMR imaging estimates of muscle volume and intramuscular fat infiltration in the thigh: Variations with muscle, gender and age","volume":"27","author":"Hogrel","year":"2015","journal-title":"Age"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1038\/ijo.2015.124","article-title":"Sarcopenic obesity and risk of new onset depressive symptoms in older adults: English longitudinal study of ageing","volume":"39","author":"Hamer","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/biof.5","article-title":"Sarcopenia of aging: Underlying cellular mechanisms and protection by calorie restriction","volume":"35","author":"Marzetti","year":"2009","journal-title":"Biofactors"},{"key":"ref_16","first-page":"177","article-title":"Clinical definition of sarcopenia","volume":"11","author":"Santilli","year":"2014","journal-title":"Clin. Cases Min. Bone Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.coi.2010.05.003","article-title":"Aging of the innate immune system","volume":"22","author":"Shaw","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18632\/aging.100531","article-title":"The role of inflammation in age-related disease","volume":"5","author":"Howcroft","year":"2013","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.ebiom.2015.09.015","article-title":"Cellular senescence and inflammatory burden as determinants of mortality in elderly people until extreme old age","volume":"2","author":"Giacconi","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_20","first-page":"130","article-title":"Exercise, inflammation and aging","volume":"3","author":"Woods","year":"2012","journal-title":"Aging Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0889-8561(02)00056-5","article-title":"Age-related inflammatory cytokines and disease","volume":"23","author":"Bruunsgaard","year":"2003","journal-title":"Immunol. Allergy Clin N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_23","first-page":"2351","article-title":"The influence of age, sex and race on the upper reference limit of serum C-reactive protein concentration","volume":"27","author":"Wener","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.arr.2008.07.002","article-title":"Molecular inflammation: Underpinnings of aging and age-related diseases","volume":"8","author":"Chung","year":"2009","journal-title":"Ageing Res. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1097\/00005768-200009000-00013","article-title":"Changes in physical activity patterns in the United States, by sex and cross-sectional age","volume":"32","author":"Caspersen","year":"2000","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a2467","DOI":"10.1136\/bmj.a2467","article-title":"Incidence of cardiovascular disease and cancer in advanced age: Prospective cohort study","volume":"337","author":"Driver","year":"2008","journal-title":"BMJ"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.2337\/dc06-0062","article-title":"Prevalence of diabetes and impaired fasting glucose in adults in the US population: NHANES survey 1999\u20132002","volume":"29","author":"Cowie","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_28","first-page":"126","article-title":"Sepsis in old age: Review of human and animal studies","volume":"5","author":"Starr","year":"2014","journal-title":"Aging Dis."},{"key":"ref_29","first-page":"487","article-title":"Dysregulated inflammation as a risk factor for pneumonia in the elderly","volume":"2","author":"Boyd","year":"2011","journal-title":"Aging Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/S1474-4422(08)70169-8","article-title":"Alzheimer\u2019s disease and vascular dementia in developing countries: Prevalence, management, and risk factors","volume":"7","author":"Kalaria","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1001\/jama.298.17.2038","article-title":"Prevalence of chronic kidney disease in the United States","volume":"298","author":"Coresh","year":"2007","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s11999-008-0625-5","article-title":"Systematic review of the prevalence of radiographic primary hip osteoarthritis","volume":"467","author":"Dagenais","year":"2009","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/ageing\/25.3.224","article-title":"Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons","volume":"25","author":"Ballou","year":"1996","journal-title":"Age Ageing"},{"key":"ref_34","first-page":"225","article-title":"Interleukin-6 and aging: Blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction","volume":"12","author":"Ershler","year":"1993","journal-title":"Lymphokine Cytokine Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/0024-3205(92)90112-3","article-title":"Increase in plasma IL-6 concentration with age in healthy subjects","volume":"51","author":"Wei","year":"1992","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0047-6374(01)00266-4","article-title":"Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women","volume":"122","author":"Ahluwalia","year":"2001","journal-title":"Mech. Ageing Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/gerona\/56.2.B81","article-title":"Interleukin-6 production does not increase with age","volume":"56","author":"Beharka","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/aje\/kwr085","article-title":"Inflammation biomarkers and risk of all-cause mortality in the RCARDS cohort","volume":"174","author":"Kabagambe","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.yexmp.2005.11.004","article-title":"Inflammation markers predicting frailty and mortality in the elderly","volume":"80","author":"DeMartinis","year":"2006","journal-title":"Exp. Mol. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1177\/0148607108324585","article-title":"Inflammation: Roles in aging and sarcopenia","volume":"32","author":"Jensen","year":"2008","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/j.1532-5415.2004.52308.x","article-title":"Inflammatory markers and incident mobility limitation in the elderly","volume":"52","author":"Penninx","year":"2004","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.psyneuen.2011.04.003","article-title":"Poorer self-related health is associated with elevated inflammatory markers among older adults","volume":"36","author":"Christian","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jamda.2013.05.009","article-title":"Proinflammatory cytokines, aging, and age-related diseases","volume":"14","author":"Michaud","year":"2013","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Golbidi, S., and Laher, I. (2013). Exercise and the aging endothelium. J. Diabetes Res.","DOI":"10.1155\/2013\/789607"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1086\/314873","article-title":"Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections","volume":"180","author":"Bruunsgaard","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1128\/CDLI.8.2.333-338.2001","article-title":"Ageing is associated with a prolonged fever in human endotoxemia","volume":"8","author":"Krabbe","year":"2001","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, J., Xia, S., Kalonis, B., Wan, W., and Sun, T. (2014). The role of oxidative stress and inflammation in cardiovascular aging. BioMed Res. Int.","DOI":"10.1155\/2014\/615312"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/gerona\/61.4.388","article-title":"Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4","volume":"61","author":"McFarlin","year":"2006","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00000441-200608000-00002","article-title":"Serum cortisol levels in patients admitted to the department of medicine: Prognostic correlations and effects of age, infection and co-morbidity","volume":"332","author":"Roash","year":"2006","journal-title":"Am. J. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1161\/01.CIR.0000115516.54550.B1","article-title":"Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women","volume":"109","author":"Johnson","year":"2004","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cca.2010.02.069","article-title":"Effect of exercise on chronic inflammation","volume":"411","author":"Beavers","year":"2010","journal-title":"Clin. Chem. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.atherosclerosis.2008.04.015","article-title":"Interleukin-18 and the risk of future cardiovascular disease among initially healthy women","volume":"202","author":"Everett","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cyto.2009.09.004","article-title":"Influences of genetic variants in interleukin-15 gene and interleukin-15 levels on coronary heart disease","volume":"49","author":"Gokkusu","year":"2010","journal-title":"Cytokine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1158\/1078-0432.CCR-08-0738","article-title":"Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence","volume":"14","author":"Caruso","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_55","first-page":"203","article-title":"Purified interleukin-1 from human monocytes stimulates acute phase protein synthesis by rodent hepatocytes in vitro","volume":"60","author":"Gauldie","year":"1987","journal-title":"Immunology"},{"key":"ref_56","first-page":"1044","article-title":"Albumin: A marker of inflammation","volume":"333","author":"Mahesh","year":"2006","journal-title":"BMJ"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.2174\/138161211798220918","article-title":"Cytokine signalling modulates blood-brain barrier function","volume":"17","author":"Pan","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Allison, D.J., and Ditor, D.S. (2014). The common inflammatory etiology of depression and cognitive impairment: A therapeutic target. J. Neuroinflamm.","DOI":"10.1186\/s12974-014-0151-1"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1017\/S1466252308001448","article-title":"Sickness behaviour, its mechanisms and significance","volume":"9","author":"Tizard","year":"2008","journal-title":"Anim. Health Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/alzrt24","article-title":"Inflammation in Alzheimer\u2019s disease: Relevance to pathogenesis and therapy","volume":"2","author":"Zotova","year":"2010","journal-title":"Alzheimers Res. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1159\/000365388","article-title":"Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: A systematic review","volume":"38","author":"Ohman","year":"2014","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/jdi.12042","article-title":"Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease","volume":"4","author":"Vinik","year":"2013","journal-title":"Diabetes Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/icb.2014.16","article-title":"From cytokine to myokine: The emerging role of interleukin-6 in metabolic regulation","volume":"92","author":"Pal","year":"2014","journal-title":"Immunol. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.bbi.2005.04.008","article-title":"Muscle-derived interleukin-6: A possible link between skeletal muscle, adipose tissue, liver and brain","volume":"19","author":"Pedersen","year":"2005","journal-title":"Brain Behav. Immun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/intimm\/dxq030","article-title":"IL-6: From its discovery to clinical applications","volume":"22","author":"Kishimoto","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.mad.2013.11.004","article-title":"Life-long endurance exercise in humans: Circulating levels of inflammatory markers and leg muscle size","volume":"134","author":"Mikkelsen","year":"2013","journal-title":"Mech. Ageing Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1023\/A:1026070911202","article-title":"Searching for the exercise factor: Is IL-6 a candidate?","volume":"24","author":"Pedersen","year":"2003","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1152\/japplphysiol.00164.2004","article-title":"The anti-inflammatory effect of exercise","volume":"98","author":"Pedersen","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/00062752-200105000-00002","article-title":"Exercise and interleukin-6","volume":"8","author":"Pedersen","year":"2001","journal-title":"Curr. Opin. Hematol."},{"key":"ref_70","first-page":"6","article-title":"Interleukin-6 in acute exercise and training; what is the biological relevance?","volume":"12","author":"Fischer","year":"2006","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.iac.2009.02.011","article-title":"Exercise, inflammation and innate immunity","volume":"29","author":"Woods","year":"2009","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.bbi.2011.02.010","article-title":"Exercise-induced myokines and their role in chronic disease","volume":"25","author":"Pedersen","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Brandt, C., and Pedersen, B.K. (2010). The role of exercise-induced myokines in muscle homeostasis and the defence against chronic diseases. J. Biomed. Biotechnol.","DOI":"10.1155\/2010\/520258"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"M999","DOI":"10.1093\/gerona\/58.11.M999","article-title":"Role of apoptosis in sarcopenia","volume":"58","author":"Leeuwenburgh","year":"2003","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_75","first-page":"1339","article-title":"Mechanisms of skeletal muscle aging: Insights from Drosophila and mammalian models","volume":"6","author":"Demontis","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.cger.2011.03.005","article-title":"Physiopathological mechanism of sarcopenia","volume":"27","author":"Walrand","year":"2011","journal-title":"Clin. Geriatr. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ekelund, U., Ward, H.A., Norat, T., Luan, J., May, A.M., Weiderpasse, E., Sharp, S.J., Overvad, K., Ostergaard, J.N., and Tjonneland, A. (2015). Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: The European Prospective Investigation into Cancer and Nutrition study (EPIC). Am. J. Clin. Nutr.","DOI":"10.3945\/ajcn.114.100065"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1056\/NEJM200105033441801","article-title":"Prevention of type 2 diabetes mellitus by changes of lifestyle among subjects with impaired glucose tolerance","volume":"344","author":"Tuomilehto","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/ageing\/afw090","article-title":"Physical activity and incidence of sarcopenia: The population-based AGES-Reykjavik study","volume":"45","author":"Mijnarends","year":"2016","journal-title":"Age Ageing"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Angevaren, M., Aufdemkampe, G., Verhaar, H.J., Aleman, A., and Vanhees, L. (2008). Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD005381.pub3"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1080\/13607861003713232","article-title":"Is exercise effective in promoting mental wellbeing in older age? A systematic review","volume":"14","author":"Windle","year":"2010","journal-title":"Aging Ment. Health"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"ii1","DOI":"10.1136\/thoraxjnl-2013-203808","article-title":"William D-C Man10, British Thoracic Society guideline on pulmonary rehabilitation in adults","volume":"68","author":"Bolton","year":"2013","journal-title":"Thorax"},{"key":"ref_83","unstructured":"NICE Guideline CG172 Myocardial Infarction\u2014Secondary Prevention. Available online: Http:\/\/www.nice.org.uk\/guidance\/cg172."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/j.1532-5415.2004.52307.x","article-title":"Physical activity, exercise and inflammatory markers in older adults","volume":"52","author":"Colbert","year":"2004","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/gerona\/55.12.M709","article-title":"Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons","volume":"55","author":"Taaffe","year":"2000","journal-title":"J. Gerontol. A Biol. Sci. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/aje\/153.3.242","article-title":"Association between physical activity and markers of inflammation in a healthy elderly population","volume":"153","author":"Geffken","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1161\/01.CIR.0000016346.14762.71","article-title":"Physical activity and hemostatic variables in elderly men","volume":"105","author":"Wannamethee","year":"2002","journal-title":"Circulation"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/gerona\/60.6.760","article-title":"Association between physical activity, physical performance and inflammatory biomarkers in an elderly population: The CHIANTI study","volume":"60","author":"Elosua","year":"2005","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1161\/CIRCULATIONAHA.112.103879","article-title":"Physical activity and inflammatory markers over 10 years: Follow-up in men and women from the Whitehall II cohort study","volume":"126","author":"Hamer","year":"2012","journal-title":"Circulation"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1093\/ajcn\/79.4.544","article-title":"Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: A randomized controlled clinical trial","volume":"79","author":"Nicklas","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3945\/ajcn.2008.26779","article-title":"Prospective study of physical fitness, adiposity and inflammatory markers in healthy middle-aged man and women","volume":"89","author":"Hamer","year":"2009","journal-title":"Am. J. Clin Nutr"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/gme.0b013e31817fcb8f","article-title":"Stronger relationship between central adiposity and C-reactive protein in older women than men","volume":"16","author":"Valentine","year":"2009","journal-title":"Menopause"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1467-842X.1997.tb01653.x","article-title":"Effects of group exercise on cognitive functioning and mood in older women","volume":"21","author":"Lord","year":"1997","journal-title":"Aust N. Z. J. Public Health"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"S504","DOI":"10.1086\/432007","article-title":"The immunopathogenesis of sepsis in elderly patients","volume":"41","author":"Opal","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"609","DOI":"10.2174\/138161210790883840","article-title":"Age-related inflammation: The contribution of different organs, tissues and systems. How to face it for therapeutic approaches","volume":"16","author":"Cevenini","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1136\/thx.2006.061002","article-title":"Theophylline for COPD","volume":"61","author":"Barnes","year":"2006","journal-title":"Thorax"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1164\/rccm.2105106","article-title":"Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease","volume":"165","author":"Culpitt","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_98","first-page":"262","article-title":"Pentoxyfylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and TNF alpha by human peripheral blood mononuclear cells","volume":"83","author":"Neuner","year":"1994","journal-title":"Immunology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S1081-1206(10)63476-X","article-title":"Anti-inflammatory effects of theophylline: Modulation of cytokine production","volume":"77","author":"Mascali","year":"1996","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8921","DOI":"10.1073\/pnas.132556899","article-title":"A molecular mechanism of the action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression","volume":"99","author":"Ito","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s00210-001-0494-x","article-title":"Theophylline inhibits NF-kappa activation and I kappa B alpha degradation in human pulmonary epithelial cells","volume":"364","author":"Ichiyami","year":"2001","journal-title":"Arch. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"Scheller","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.imr.2014.09.007","article-title":"Exercise-induced myokines in health and metabolic diseases","volume":"3","author":"So","year":"2014","journal-title":"Integr. Med. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/gerona\/glv083","article-title":"Cytokines and postoperative delirium in older patients undergoing major elective surgery","volume":"70","author":"Vasunilashorn","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.amjmed.2003.05.001","article-title":"Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study","volume":"115","author":"Roubenoff","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1523-1755.2005.00200.x","article-title":"IL-10, IL-6 and TNF-alpha: Central factors in the altered cytokine network of uraemia\u2014the good, the bad and the ugly","volume":"67","author":"Stenvinkel","year":"2005","journal-title":"Kidney Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1046\/j.1532-5415.2003.51407.x","article-title":"Insulin-like growth factor 1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study","volume":"51","author":"Payette","year":"2003","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1183\/09031936.94.07020223","article-title":"Theophylline suppresses the release of TNF alpha by blood monocytes and alveolar macrophages","volume":"7","author":"Spatafora","year":"1994","journal-title":"Eur. Respir. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1248\/bpb.18.1405","article-title":"Effect of theophylline on the production of IL-1 beta, TNF alpha and IL-8 by human peripheral blood mononuclear cells","volume":"18","author":"Yoshimura","year":"1995","journal-title":"Biol. Pharm. Bull."},{"key":"ref_110","first-page":"10","article-title":"The study of tolerability and safety of theophylline given along with formoterol plus budesonide in COPD","volume":"9","author":"Subramanian","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrmicro2745","article-title":"Modulating immunity as a therapy for bacterial infections","volume":"10","author":"Hancock","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/01.ccm.0000474919.64656.12","article-title":"Effect of the use of theophylline and sepsis outcomes","volume":"43","author":"Shih","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"492901","DOI":"10.1155\/2012\/492901","article-title":"Low dose theophylline showed an inhibitory effect on the production of IL-6 and IL-8 in primary lung fibroblasts from patients with COPD","volume":"2012","author":"Zhang","year":"2012","journal-title":"Mediat. Inflamm"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/07315724.1996.10718616","article-title":"The effect of theophylline on metabolic rate in COPD patients","volume":"15","author":"Mosire","year":"1966","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/thx.2008.103432","article-title":"Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD","volume":"64","author":"Cosio","year":"2009","journal-title":"Thorax"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2174\/187221411797265890","article-title":"Immunomodulatory properties of thalidomide analogs: Pomalidomide and lenalidomide, experimental and therapeutic applications","volume":"5","author":"Bodera","year":"2011","journal-title":"Recent Pat. Endocr. Metab. Immune Drug Discov."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.burns.2007.01.007","article-title":"Thalidomide decreases the plasma levels of IL-1 and TNF following burn injury: Is it the new drug for modulation of systemic inflammatory response","volume":"34","author":"Eski","year":"2008","journal-title":"Burns"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/jcsm.12074","article-title":"Anti-sarcopenic effects of diamino-diphenyl sulfone observed in elderly female leprosy survivors: A cross-sectional study","volume":"7","author":"Lee","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_119","first-page":"55","article-title":"Chloroquine and hydroxychloroquine equally affect TNF alpha, IL-6 and IF gamma production by peripheral blood mononuclear cells","volume":"24","author":"Dijkmans","year":"1997","journal-title":"J. Rheumatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"626.e9","DOI":"10.1016\/j.jamda.2013.04.012","article-title":"Nonsteroidal anti-inflammatory drug (NSAID) use and sarcopenia in older people: Results from the ilSIRENTE study","volume":"14","author":"Landi","year":"2013","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/S0735-1097(00)01121-9","article-title":"Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy","volume":"37","author":"Ohtsuka","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ulleryd, M.A., Bernberg, E., Yang, L.J., Bergstrom, G.M.L., and Johansson, M.E. (2014). Metoprolol reduces pro-inflammatory cytokines and atherosclerosis in ApoE\u2212\/\u2212 Mice. BioMed Res. Int.","DOI":"10.1155\/2014\/548783"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.bcp.2013.04.009","article-title":"Statins protect human endothelial cells from TNF-induced inflammation via ERK5 activation","volume":"85","author":"Wu","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2174\/1871530315666150316124019","article-title":"metformin and inflammation: Its potential beyond glucose-lowering effect","volume":"15","author":"Saisho","year":"2015","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.2337\/db15-0090","article-title":"Pleiotropic benefits of metformin: Macrophage targeting its anti-inflammatory mechanisms","volume":"64","author":"Hattori","year":"2015","journal-title":"Diabetes"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1124\/jpet.112.191759","article-title":"Sarcopenia: Pharmacology of today and tomorrow","volume":"343","author":"Brotto","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Geriatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3417\/2\/1\/6\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:26:20Z","timestamp":1760207180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3417\/2\/1\/6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,17]]},"references-count":126,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["geriatrics2010006"],"URL":"https:\/\/doi.org\/10.3390\/geriatrics2010006","relation":{},"ISSN":["2308-3417"],"issn-type":[{"value":"2308-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,17]]}}}