Abstract
-
Cancer is a symptom of violations of controlled biological circadian rhythms.
Living long is a biological process characterized by progressive alterations in tissue/organ function, often associated with increased risk of chronic diseases. Among major theories of aging are retardation of immune response dynamics, increased free radicals (oxido-redox imbalance) and increased genetic mutations. These age-associated biological changes cause minor or major readjustments of organs systems known as biological senescent and immunosenescent. In this chapter, the focus will be to discuss that these changes are interdependent processes and persistent or unresolved inflammation (oxidative stress) is a common denominator increasing the risk of nearly all age-associated chronic illnesses and site-specific cancers. Attempts were made to demonstrate the interrelationships between unresolved inflammation and the induction of immune response shifts in immune-responsive and immune-privileged tissues in initiation and progression of major chronic illnesses. Evaluation of scattered data on aging process suggests that in general, longevity is a biologically intrinsic process characterized by steady and progressive declines in the integrity and function of organs/tissues. However, the rate of susceptibility and severity to illnesses vary among individuals due to complex combination of interactions and heterogeneities between intrinsic and extrinsic factors that would determine the biology of aging. Strategies for reducing oxidative stress or correcting the balance between Yin and Yang response profiles of acute inflammation may prove to be important targets for delaying or preventing the onset of disabling illnesses and reducing the cost of sick-care.
We have confused illness with the process of aging, which can be thoroughly healthy. Illness is not a necessary part of aging!
Dr. Charles Eugster, 94-year-old World Master Rowing Champion.
This is a preview of subscription content, log in via an institution to check access.
References
Komiya K, Ishii H, Kadota J. Healthcare-associated pneumonia and aspiration pneumonia. Aging Dis. 2014;6:27–37.
Hedlund J. Community-acquired pneumonia requiring hospitalisation. Factors of importance for the short-and long term prognosis. Scand J Infect Dis. 1995;97(Suppl):1–60.
Swenson CE, Sadikot RT. Achromobacter respiratory infections. Ann Am Thorac Soc. 2015;12:252–8.
Komiya K, Ishii H, Kushima H, Sato S, Kimura H, et al. Physicians’ attitudes toward the definition of “death from age-related physical debility” in deceased elderly with aspiration pneumonia. Geriatr Gerontol Int. 2013;13:586–90.
Bruce AM, Spencer JM. Prevalence of community-acquired methicillin-resistant Staphylococcus Aureus in a private dermatology office. J Drugs Dermatol. 2008;7:751–5.
Mpenge MA, MacGowan AP. Ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia. Ther Clin Risk Manag. 2015;11:565–79. doi:10.2147/TCRM.S75412. eCollection 2015
Ewig S, Welte T, Chastre J, Torres A. Rethinking the concepts of community-acquired and health-care-associated pneumonia. Lancet Infect Dis. 2010;10:279–87.
Health Protection Agency Surveillance of Healthcare Associated Infections Report. 2008. [Accessed April 29, 2014]. Available from: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1216193833496.
Torok E, Moran E, Cooke F. Oxford handbook of infectious diseases and microbiology. Oxford: Oxford University Press; 2009.
Attridge RT, Frei CR. Health care-associated pneumonia: an evidence-based review. Am J Med. 2011;124:689–97.
Chalmers JD, Taylor JK, Singanayagam A, Fleming GB, Akram AR, et al. Epidemiology, antibiotic therapy, and clinical outcomes in health care-associated pneumonia: a UK cohort study. Clin Infect Dis. 2011;53:107–13.
DHHS. DHHS report: Health United States with special feature on prescription drugs. Washington, DC: DHHS; 2013.
Riquelme R, Torres A, El-Ebiary M, de la Bellacasa JP, Estruch R, Mensa J, Fernández-Solá J, Hernández C, Rodriguez-Roisin R. Community-acquired pneumonia in the elderly: a multivariate analysis of risk and prognostic factors. Am J Respir Crit Care Med. 1996;154:1450–5.
Sader HS, Farrell DJ, Jones RN. Antimicrobial susceptibility of gram-positive cocci isolated from skin and skin-structure infections in European medical centres. Int J Antimicrob Agents. 2010;36:28–32.
Terracciano A, Löckenhoff CE, Zonderman AB, Ferrucci L, Costa PT. Personality predictors of longevity: activity, emotional stability, and conscientiousness. Psychosom Med. 2008;70:621–7.
Boucher H, Miller LG, Razonable RR. Serious infections caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2010;51(Suppl 2):S183–97.
Baik I, Curhan GC, Rimm EB, Bendich A, Willett WC, Fawzi WW. A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women. Arch Intern Med. 2000;160:3082–8. Diet
Davis K, Stremikis K, Schoen C, Squires D. Mirror, Mirror on the Wall, 2014 Update: How the U.S. Health Care System Compares Internationally, The Commonwealth Fund, June 2014.
McNulty J, Khera N. Financial hardship-an unwanted consequence of cancer treatment. Curr Hematol Malig Rep. 2015;26:205–12. [Epub ahead of print]
Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 2004;52:80–5.
Khatami M. Cancer research and therapy: scam of century – promote immunity [Yin-Yang], 2016; ISBN-10:153043100X;ISBN-13:978–1530431007; Amazon-Createspace p1–166, http://www.createspace.com/6123573.
Khatami M. Chronic inflammation: synergistic interactions of recruiting macrophages (TAMs) eosinophils (Eos) with host mast cells (MCs) and tumorigenesis un CALTs. MCSF, suitable biomarker for cancer diagnosis! Cancers (Basel). 2014;6:297–322.
Khatami M. Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity: a common denominator mapping chronic diseases. Cell Biochem Biophys. 2009;55:55–79.
Khatami M. Unresolved inflammation and cancer: loss of natural immune surveillance as the correct ‘target’ for therapy! Seeing the ‘elephant’ in the light of logic. Cell Biochem Biophys. 2012;62:501–9.
Khatami M. Inflammation, aging and cancer: Friend or foe? In: Khatami M, editor. Inflammation, Chronic Diseases and Cancer-Cell and Molecular Biology, Immunology and Clinical Bases. Rejeka, Croatia: InTech Publishing., [ISBN 978-953-51-0102; 2012. p. 3–30.
Khatami M. Unresolved inflammation: ‘immune tsunami’ or erosion of integrity in immune-privileged and immune-responsive tissues and acute and chronic inflammatory diseases or cancer. Expert Opin Biol Ther. 2011;11:1419–32.
Williams GC. Pleiotropy, natural selection and the evolution of senescence. Evolution. 1957;11:398–411.
Burnet M: Cancer: a biological approach. The processes of control. Br Med J.. 1957.
Lee RD. Rethinking the evolutionary theory of aging: transfers, not births, shape senescence in social species. Proc Natl Acad Sci (USA). 2003;100:9637–42.
Khatami M. ‘Yin and Yang’ in inflammation: duality in innate immune cell function and tumorigenesis. Expert Opin Biol Ther. 2008;8:1461–71.
Hakim FT, Flomerfelt FA, Boyiadzis M, Gress RE. Aging, immunity and cancer. Current Opin Immunol. 2004;18:151–8.
Knight JA. The biochemistry of aging. Adv Clin Chem. 2000;35:1–62.
Fleg JL, Morrell CH, Bos AG, Brant LJ, Talbot LA, Wright JG, et al. Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation. 2005;112:674–82.
Franceschi C, Bonafè M, Valensin S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000;18:1717–20.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.
Baggio G, Donazzan S, Monti D, Mari D, Martini S, Gabelli C, Dalla Vestra M, Previato L, Guido M, Pigozzo S, Cortella I, Crepaldi G, Franceschi C. Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors. FASEB J. 1998;12:433–7.
Kipling D, Davis T, Ostler EJ, Faragher RG. What can progeroid syndromes tell about human aging? Science. 2004;305:1426–31.
Brod SA. Unregulated inflammation shortens human functional longevity. Inflamm Res. 2000;49:561–70.
Bruunsgaard H. The clinical impact of systemic low-level inflammation in elderly populations. With special reference to cardiovascular disease, dementia and mortality. Dan Med Bull. 2006;53:285–309.
Quaglino D, Ginaldi L, Furia N, De Martinis M. The effect of age on hemopoiesis. Aging (Milano). 1996;8:1–12.
McGlauchlen KS, Vogel LA. Ineffective humoral immunity in the elderly. Microbes Infect. 2003;5:1279–84.
Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6:508–19.
Meyer KC. Lung infection and aging. Ageing Res Rev. 2004;3:55–67.
Croce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol. 2007;14:55–61.
Blagosklonny MV. Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle. 2006;5:2087–102.
Rafi A, Castle SC, Uyemura K, Makinodan T. Immune dysfunction in the elderly and its reversal by antihistamines. Biomedicine & Pharmacology. 2003;57:246–50.
Ignarro LJ, Balestrieri ML, Napoli C. Nutrition, physical activity, and cardiovascular disease: an update. Cardiovasc Res. 2007;73:326–40.
Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C. Molecular inflammation: Underpinning of aging and age-related diseases. Ageing Res Rev. 2008;8:18–30.
Arking R. The Biology of Aging: Observarion and principles. 2nd ed. Sunderland, MA, USA: Sinauer Associates Inc.; 1998. p. 153–250.
Khatami M. Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. Am J Ther. 2005;12:117–26.
Culmsee C, Landshamer S. Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res. 2006;3:269–83.
Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, Franceschi C, Passeri M. The immune system in extreme longevity. Exp Gerontol. 2008;43:61–5.
Ginaldi L, DiBenedetto MC, DeMartinis M. Osteoporosis inflammation and ageing. Immun Ageing. 2005;2:14. doi:10.1186/1742-4933-2-14.
Keibel A, Singh V, Sharma MC. Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des. 2009;15:1949–55.
Davalos AR, Coppe JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010;29:273–83.
Sohal RS, Orr WC. The redox stress hypothesis of aging. Free Radic Biol Med. 2012;52:539–55.
Huppertz B, Ghosh D, Sengupta J. An integrative view on the physiology of human early placental villi. Prog Biophys Mol Biol. 2014;114:33–48.
Dunlop K, Cedrone M, Staples JF, Regnault TR. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity. Forum Nutr. 2015;7:1202–16.
Moreno E, Rhiner C. Darwin’s multicellularity: from neurotrophic theories and cell competition to fitness fingerprints. Curr Opin Cell Biol. 2014;31:16–22.
Moreno E, Basler K. Morata G: cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416:755–9.
Virchow R. Cellular pathology. London: Churchill; 1860.
De Loof A, De Haes W, Boerjan B, Schoofs L. The fading electricity theory of aging: the missing biophysical principal? Aging Res Rev. 2013;12:58–66.
Lucia U. The Gouy-Stodola theorem in bioenergetic analysis of living systems (irreversibility in bioenergetics of living systems). Energies. 2014;7:5717–39.
Guzmán-Gutiérrez E, Arroyo P, Salsoso R, Fuenzalida B, Sáez T, Leiva A, Pardo F, Sobrevia L. Role of insulin and adenosine in the human placenta microvascular and macrovascular endothelial cell dysfunction in gestational diabetes mellitus. Microcirculation. 2014;21:26–37.
Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.
Harman D. The biologic clock: the mitochondria? J Am Geriatr Soc. 1972;20:145–7.
Mittledorf JJ. Adaptive aging in the context of evolutionary theory. Biochemistry (Mosc). 2012;77:716–25.
Weinert BT, Timiras PS. Invited review: theories of aging. J Appl Physiol. 2003;95:1706–16.
Arellanes-Licea E, Caldelas I, De Ita-Pérez D, Díaz-Muñoz M. The circadian timing system: a recent addition in the physiological mechanisms underlying pathological and aging processes. Aging Dis. 2014;5:406–18. doi:10.14336/AD.2014.0500406. eCollection 2014
Nader N, Chrousos GP, Kino T. Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J. 2009;23:1572–83.
Vielhaber E, Eide E, Rivers A, Gao ZH, Virshup DM. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon. Mol Cell Biol. 2000;13:4888–99.
Jones DP. Redox theory of aging. Redox Biol. 2015;5:71–8.
Chung HY, Kim HJ, Kim KW, Choi JS, Yu BP. Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction. Microsc Res Tech. 2002;59:264–72.
Hardeland R. Melatonin and the theories of aging: a critical appraisal of melatonin’s role in antiaging mechanisms. J Pineal Res. 2013;55:325–56.
Rustin P, von Kleist-Retzow JC, Vajo Z, Rotig A, Munnich A. Detective mitochondria, free radicals, cell death-reality or myth-ochrondria. Mech Age Develop. 2000;114:201–6. http://www.britannica.com/EBchecked/topic/271624/Horace
Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H. Trends in oxidative aging theories. Free Radic Biol Med. 2007;43:477–503.
Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003;299:1346–51.
Lapointe J, Hekimi S. When a theory of aging ages badly. Cell Mol Life Sci. 2010;67:1–8.
Vitale G, Salvioli S, Franceschi C. Oxidative stress and the ageing endocrine system. Nat Rev Endocrinol. 2013;9:228–40.
Khatami M. Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint? Perspective. Clin Trans Med. 2016;5:35. doi:10.1186/s40169-016-0108-3. Epub 2016 Aug 23
Khalyavkin AV, Krut’ko VN. Early thymus involution--manifestation of an aging program or a program of Development? Biochemistry (Mosc). 2015 Dec;80(12):1622–5. doi:10.1134/S0006297915120111.
Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998;78:547–81.
Margulis L. Symbiosis and evolution. Sci Am. 1971;225:48–57.
Beckman JS, Koppenol WH. Nitric oxide, superoxide and peroxynitrite: The good, the bad, and the ugly. Am. J. Physiol. (Cell Physiol.). 1996;271:C1424–37.
McCann SM, Mastronardi C, de Laurentiis A, Rettori V. The nitric oxide theory of aging revisited. Ann N Y Acad Sci. 2005;1057:64–84.
Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 4th ed. Oxford: Oxford University Press; 2007.
Liu X, Miller MJS, Joshi MS, Thomas DD, Lancaster JR Jr. Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes. Proc Natl Acad Sci U S A. 1998;95:2175–9.
Madej E, Folkes LK, Wardman P, Czapski G, Goldstein S. Thiyl radicals react with nitric oxide to form S-nitrosothiols with rate constants near the diffusion-controlled limit. Free Radic Biol Med. 2008;44:2013–8.
Eiserich JP, Butler J, Van Der Vliet A, Cross CE, Halliwell B. Nitric oxide rapidly scavenges tyrosine and tryptophan radicals. Biochem J. 1995;310:745–9.
Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun. 1993;18:195–9.
Zorov DB, Plotnikov EY, Silachev DN, Zorova LD, Pevzner IB, Zorov SD, Babenko VA, Jankauskas SS, Popkov VA, Savina PS. Microbiota and mitobiota. Putting an equal sign between mitochondria and bacteria. Biochemistry (Mosc). 2014;79:1017–31.
Klass M, Nguyen PN, Dechavigny A. Age-correlated changes in the DNA template in the nematode Caenorhabditis elegans. Mech Ageing Dev. 1983;22:253–63.
Gems D, Doonan R. Antioxidant defense and aging in C. elegans: is the oxidative damage theory of aging wrong? Cell Cycle. 2009;8:1681–7.
Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol. Rev. 2010;90:859–904.
Yamaza H, Chiba T, Higami Y, Shimokawa I. Lifespan extension by caloric restriction: an aspect of energy metabolism. Microsc Res Tech. 2002;59:325–30.
Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915–22.
Kim CI. Treatment: nutrition alimentotherapy. Geriatrics. Seoul: Seoul National University Press; 1997. p. 122–31. Diet
DeBoer S, Olson FK, Schultz C, Starkson S, Wiitanen EM. Geriatric nutrition. In: Nelson JK, Mozness KE, Jensen MD, Gastineau CF, editors. Diet manual. 7th ed. St. Louis: Mosby; 1994. p. 58–70.
Harrington LA, Harley CB. Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev. 1988;43:71–8.
Feng J, Bussière F, Hekimi S. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell. 2001;1:633–44.
Doonan R, McElwee JJ, Matthijssens F, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 2008;22:3236–41.
Brys K, Castelein N, Matthijssens F, Vanfleteren JR, Braeckman BP. Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans. BMC Biol. 2010;8:91. doi:10.1186/1741-7007-8-91.
Yasuda K, Adachi H, Fujiwara Y, Ishii N. Protein carbonyl accumulation in aging dauer formation-defective (daf) mutants of Caenorhabditis elegans. J Gerontol A. 1999;54:B47–51.
Minniti AN, Cataldo R, Trigo C, et al. Methionine sulfoxide reductase a expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans. Aging Cell. 2009;8:690–705.
Honda Y, Honda S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 1999;13:1385–93.
Petriv OI, Rachubinski RA. Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem. 2004;279:19996–20001.
Back P, Braeckman BP, Matthijssens F. ROS in aging Caenorhabditis elegans: damage or signaling? Oxidative Med Cell Longev. 2012;608478:2012. doi:10.1155/2012/608478. Epub 2012 Aug 15.
Jee C, Vanoaica L, Lee J, Park BJ, Ahnn J. Thioredoxin is related to life span regulation and oxidative stress response in Caenorhabditis elegans. Genes Cells. 2005;10(12):1203–10.
Hernández-García D, Wood CD, Castro-Obregón S, Covarrubias L. Reactive oxygen species: a radical role in development? Free Radic Biol Med. 2010;49:130–43.
Melov S, Lithgow GJ, Fischer DR, Tedesco PM, Johnson TE. Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans. Nucleic Acids Res. 1995;23:1419–25.
Honda Y, Tanaka M, Honda S. Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans. Exp Gerontol. 2008;43:520–9.
Bokov A, Chaudhuri A, Richardson A. The role of oxidative damage and stress in aging. Mech Ageing Dev. 2004;125:811–26.
Matthijssens F, Back P, Braeckman BP, Vanfleteren JR. Prooxidant activity of the superoxide dismutase (SOD)-mimetic EUK-8 in proliferating and growth-arrested Escherichia coli cells. Free Radic Biol Med. 2008;45:708–15.
Hebert DN, Molinari M. In and out of the ER: protein folding, quality control, degradation, and related human diseases. Physiol Rev. 2007;87:1377–408.
Taub J, Lau JF, Ma C, et al. A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature. 1999;399:162–6.
Van Raamsdonk JM, Hekimi S. Reactive oxygen species and aging in Caenorhabditis elegans: causal or casual relationship? Antioxid Redox Signal. 2010;13:1911–53.
Toldo S, Seropian IM, Mezzaroma E, Van Tassell BW, Salloum FN, Lewis EC, et al. Alpha-1 antitrypsin inhibits caspase-1 and protects from acute myocardial ischemia-reperfusion injury. J Mol Cell Cardiol. 2011;51:244–51.
Orrenius S, Gogvadze V, Zhivotovsky B. Calcium and mitochondria in the regulation of cell death. Biochem Biophys Res Commun. 2015;460:72–81.
Orrenius S. Reactive oxygen species in mitochondria-mediated cell death. Drug Metab Rev. 2007;39:443–55.
Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis. 2007;12:913–22.
Apel K, Hirt H. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol. 2004;55:373–99.
Cetrullo S, D’Adamo S, Tantini B, Borzi RM, Flamigni F. mTOR, AMPK, and Sirt1: key players in metabolic stress management. Crit Rev Eukaryot Gene Expr. 2015;25:59–75.
Wataya-Kaneda M. Mammalian target of rapamycin and tuberous sclerosis complex. J Dermatol Sci. 2015;S0923-1811(15):00154–1.
Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene. 2006;25:6347–60.
Albert V, Hall MN. mTOR signaling in cellular and organismal energetics. Curr Opin Cell Biol. 2014;33C:55–66.
Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010;40:310–22.
Lakowski B, Hekimi S. The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci USA. 1998;95(22):13091–6.
Bishop NA, Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature. 2007;447(7144):545–9.
Miller RA. The aging immune system: primer and prospectus. Science. 1996;273:70–4.
Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, Cesari M, Nourhashemi F. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877–82.
Makinodan T, Kay MM. Age influence on the immune system. Adv Immunol. 1980;29:287–330.
Qi Q, Zhang DW, Weyand CM, Goronzy JJ. Mechanisms shaping the naïve T cell repertoire in the elderly thymic involution or peripheral homeostatic proliferation? Exp Gerontol. 2014;54:71–4.
Appay V, Sauce D. Naive T cells: the crux of cellular immune aging? Exp Gerontol. 2014;54:90–3.
Ghia P, Melchers F, Rolink AG. Age-dependent changes in B lymphocyte development in man and mouse. Exp Gerontol. 2000;35:159–65.
Chen H, Zheng X, Zheng Y. Lamin-B in systemic inflammation, tissue homeostasis, and aging. Nucleus. 2015;15:1–4.
Fulop T, Larbi A, Kotb R, de Angelis F, Pawelec G. Aging, immunity, and cancer. Discov Med. 2011;61:537–50.
Blaseser A, McGlauchlen K, Vogel LA. Aged B lymphocytes retain their ability to express surface markers but are dysfunctional in their proliferative capacity during early activation event. Immun Ageing. 2008;5:5–15. doi:10.1186/1742-4933-5-15.
Powers DC, Belshe RB. Effect of age on cytotoxic T lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine. J Infect Dis. 1993;167:584–92.
Allain TJ, Dhesi J. Hypovitaminosis D in older adults. Gerontology. 2003;49:273–8.
Sawyer DT. Oxygen chemistry. New York: Oxford University Press; 1991.
Borel P, Caillaud D, Cano NJ. Vitamin d bioavailability: state of the art. Crit Rev Food Sci Nutr. 2015;55:1193–205.
Thompson P, Khatami M, Baglole CJ, Sun J, Harris SA, Moon EY, et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015;36(Suppl 1):S232–53. doi:10.1093/carcin/bgv038.
Inoue H, Hisamoto N, An JH, et al. The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Gene Dev. 2005;19:2278–83.
Cross AR, Segal AW. The NADPH oxidase of professional phagocytes—prototype of the NOX electron transport chain systems. Biochim Biophys Acta. 2004;1657:1–22.
Cochemé HM, Quin C, McQuaker SJ, et al. Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab. 2011;13:340–50.
Mishina NM, Tyurin-Kuzmin PA, Markvicheva KN, et al. Does cellular hydrogen peroxide diffuse or act locally? Antioxid Redox Signal. 2011;14:1–7.
Kim SG, Buel GR, Blenis J. Nutrient regulation of the mTOR complex 1 signaling pathway. Mol Cells. 2013;35:463–73.
Edeas M. Strategies to target mitochondria and oxidative stress by antioxidants: key points and perspectives. Pharm Res. 2011;28:2771–9.
Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gelinas C, Fan Y, Nelson DA, Jin S, White E. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10:51–64.
Krtolica A, Campisi J. Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol. 2002;34:1401–14.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49:1603–16.
McCord JM, Edeas MA. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother. 2005;59:139–42.
Stone JR, Yang S. Hydrogen Peroxide: a signaling messenger. Antiox Redox Signaling. 2006;8:243–70.
Ungvari Z, Labinskyy N, Mukhopadhyay P, et al. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol. 2009;297:H1876–81.
Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother. 2004;58:39–46.
Kroemer G. Autophagy: a druggable process that is deregulated in aging and human disease. J Clin Invest. 2015;125:1–4. doi:10.1172/JCI78652. Epub 2015 Jan 2
Galluzzi L, Zamzami N, de La Motte RT, Lemaire C, Brenner C, Kroemer G. Methods for the assessment of mitochondrial membrane permeabilization in apoptosis. Apoptosis. 2007;12:803–13.
Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;273(5271):59–63.
Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M, Kroemer G. Mitochondrial gateways to cancer. Mol Asp Med. 2010;31:1–20.
Pedersen PL. Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res. 1978;22:190–274.
Kiebish MA, Han X, Cheng H, Chuang JH, Seyfried TN. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res. 2008;49:2545–456.
Cloonan SM, Choi AMK. Mitochondria: commanders of innate immunity and disease? Curr Opin Immunol. 2012;24:32–40.
Takahashi E, Sato M. Anaerobic respiration sustains mitochondrial membrane potential in a prolyl hydroxylase pathway-activated cancer cell line in a hypoxic microenvironment. Am J Physiol Cell Physiol. 2014;306:C334–42.
Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hasimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11:37–51.
Frezza C, Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Sem Cancer Bio. 2009;l19:4–11.
Zhang XV, Martin ST. Driving parts of Krebs Cycle in reverse through mineral photochemistry. J Am Chem Soc. 2006;128:16032–3.
Poyton RO, Ball KA, Castello PR. Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab. 2009;20:332–40.
Sharma G, Sharma AR, Seo EM, Nam JS. Genetic polymorphism in extracellular regulators of Wnt signaling pathway. Biomed Res Int. 2015;2015:847529.
Lovering RC, Camon EB, Blake JA, Diehl AD. Access to immunology through the gene ontology. Immunology. 2008;125:154–60.
Collins LV, Hajizadeh S, Holme E, Jonsson I-M, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J Leukoc Biol. 2004;75:995–1000. doi:10.1189/jlb.0703328.
Landis GN, Tower J. Superoxide dismutase evolution and life span regulation. Mech Ageing Dev. 2005;126:365–79.
De Magalhaes JP, Wuttke D, Wood SH, Plank M, Vora C. Genome-environment interactions that modulate aging: powerful targets for drug discovery. Pharmacol Rev. 2012;64:88–101.
Vijg J, Hasty P. Aging and p53: getting it straight. A commentary on a recent paper by Gentry and Venkatachalam. Aging Cell. 2005;4:335–8.
Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789–99.
Fukada S, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, et al. Genetic background affects properties of satellite cells and mdx phenotypes. Am J Pathol. 2010;176:2414–24.
Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. 1999;96:701–12.
Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97:527–638.
Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C, et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 2007;447:686–90.
Nagata S, Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995;16:39–43.
Alves H, Munoz-Najar U, De Wit J, Renard AJ, Hoeijmakers JH, Sedivy JM, et al. A link between the accumulation of DNA damage and loss of multi-potency of human mesenchymal stromal cells. J Cell Mol Med. 2010;14:2729–38.
Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A. 2012;109:10522–7.
Jinnah HA, de Gregorio L, Harris JC, Nyhan WL, O’Neill JP. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res. 2000;463:309–26.
Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.
Slagboom PE, Droog S, Boomsma DI. Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet. 1994;55:876–82.
Armanios M. Syndromes of telomere shortening. Ann Rev Genomics HumGenet. 2009;10:45–61.
Noebels J. Pathway-driven discovery of epilepsy genes. Nat Neurosci. 2015;18:344–50.
Greider CW. Telomeres and senescence: the history, the experiment, the future. Curr Biol. 1998;8:R178–81.
Savage SA, Bertuch AA. The genetics and clinical manifestations of telomere biology disorders. Genet Med. 2010;12:753–64.
Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353–65.
Diaz de LA, Cronkhite JT, Katzenstein AL, Godwin JD, Raghu G, Glazer CS, Rosenblatt RL, Girod CE, Garrity ER, Xing C, Garcia CK. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010;5:e10680.
Son NH, Murray S, Yanovski J, Hodes RJ, Weng N. Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol. 2000;165:1191–6.
Gadalla SM, Cawthon R, Giri N, Alter BP, Savage SA. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. Aging (Albany, NY). 2010;2:867–74.
Hiyama E, Hiyama K. Telomere and telomerase in stem cells. Br J Cancer. 2007;96:1020–4.
Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med. 2006;12:1133–8.
Weng NP. Telomeres and immune competency. Curr Opin Immunol. 2012;24:470–5.
Weng NP, Levine BL, June CH, Hodes RJ. Human naive and memory T lymphocytes differ in telomeric length and replicative potential. Proc Natl Acad Sci U S A. 1995;92:11091–4.
Chou JP, Effros RB. Tcell replicative senescence in human aging. Curr Pharm Des. 2013;19(9):1680–98.
Wong JM, Collins K. Telomere maintenance and disease. Lancet. 2003;362:983–8.
Bjornson CR, Cheung TH, Liu L, Tripathi PV, Steeper KM, Rando TA. Notch signaling is necessary to maintain quiescence in adult muscle stem cells. Stem Cells. 2012;30:232–42.
Sharpless NE, DePinho RA. Telomeres, stem cells senescence and cancer. J Clin Invest. 2004;113:160–8.
Bohr VA, Anson RM. DNA damage, mutation and fine structure DNA repair in aging. Mutat Res. 1995;338:25–34.
Medová M, Aebersold DM, Zimmer Y. The molecular crosstalk between the MET receptor tyrosine kinase and the DNA damage response-biological and clinical aspects. Cancers. 2014;6:1–27.
Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CA. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature. 2014;505:641–7.
Huang Q, Lan F, Wang X, Yu Y, Quyang X, Zheng F, et al. IL-1beta-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9. Mol Cancer. 2014;13:18. doi:10.1186/1476-4598-13-18.
Ebert MP, Fei G, Kahmann S, et al. Increased beta-catenin mRNA levels and mutational alterations of the APC and beta-catenin gene are present in intestinal-type gastric cancer. Carcinogenesis. 2002;23:87–91.
Resende C, Ristimaki A, Machado JC. Genetic and epigenetic alteration in gastric carcinogenesis. Helicobacter. 2010;15:34–9.
Vogiatzi P, Vindigni C, Roviello F, Renieri A, Giordano A. Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis. J Cell Physiol. 2007;211:287–95.
Marimuthu A, Jacob HK, Jakharia A, et al. Gene expression profiling of gastric cancer. J Proteomics Bioinform. 2011;4:74–82.
Pasini FS, Zilberstein B, Snitcovsky I, et al. A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma. J Gastroenterol. 2013;49(11):1453–66.
Liu N, Liu X, Zhou N, Wu Q, Zhou L, Li Q. Gene expression profiling and bioinformatics analysis of gastric carcinoma. Exp Mol Pathol. 2014;96(3):361–6.
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.
Jinawath N, Furukawa Y, Hasegawa S, et al. Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray. Oncogene. 2004;23:6830–44.
Hasegawa S, Furukawa Y, Li M, et al. Genome-wide analysis of gene expression in intestinal-type gastric cancers using a complementary DNA microarray representing 23, 040 genes. Cancer Res. 2002;62:7012–7.
Dallaire A, Garand C, Paquel ER, et al. Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis eleganswrn-1 reveals the importance of this microRNA in accelerated aging. Aging (Albany NY). 2012;4:636–47.
Honeywell DR, Cabrita MA, Zhao H, Dimitroulakos J, Addison CL. miR-105 inhibits prostate tumour growth by suppressing CDK6 levels. PLoS One. 2013;8:e70515.
Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.
Hsu SD, Lin FM, Wu WY, et al. miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 2011;39(Database issue):D163–9.
Zahn JM, Poosala S, Owen AB, et al. AGEMAP: a gene expression database for aging in mice. PLoS Genet. 2007;3:e201.
Card DA, Hebbar PB, Li L, et al. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol Cell Biol. 2008;28(20):6426–38.
Sirotkin AV, Laukova M, Ovcharenko D, Brenaut P, Mlyncek M. Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. J Cell Physiol. 2010;223:49–56.
Gaur A, Jewell DA, Liang Y, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.
Li CP, Huang TS, Chao Y, Chang FY, Whang-Peng J, Lee SD. Advantages of assaying telomerase activity in ascites for diagnosis of digestive tract malignancies. World J Gastroenterol. 2004;10:2468–71.
Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3:459–65.
Hingorani SR, Tuveson DA. Ras redux: rethinking how and where Ras acts. Curr Opin Genet Dev. 2003;13:6–13.
Kirma N, Luthra R, Jones J, Liu Y-G, Nair HB, Mandava U, Tekmal RR. Overexpression of the colony-stimulating factor (CSF-1) and/or its receptor c-fms in mammary glands of transgenic mice results in hyperplasia and tumor formation. Cancer Res. 2004;64:4162–70.
Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ. Increasing complexity of Ras signaling. Oncogene. 1998;17:1395–413.
Vaziri H, Benchimol S. From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging. Exp Gerontol. 1996;31:295–301.
Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell. 2002;109:335–46.
Thomson JM, Gaucher EA, Burgan MF, De Kee DW, Li T, Aris JP, Benner SA. Resurrecting ancestral alcohol dehydrogenases from yeast. Nat Genet. 2005;37:630–5.
Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1 a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002;71:198–203.
Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genetics. 2009;10:704–14.
Otero M, Plumb DA, Tsuchimochi K, et al. E74-like factor 3 (ELF3) impacts on matrix metalloproteinase 13 (MMP13) transcriptional control in articular chondrocytes under proinflammatory stress. J Biol Chem. 2012;287:3559–72.
Gayen JR, Zhang K, RamachandraRao SP, et al. Role of reactive oxygen species in hyperadrenergic hypertension: biochemical, physiological, and pharmacological evidence from targeted ablation of the chromogranin a (Chga) gene. Circ Cardiovasc Genet. 2010;3:414–25.
Xiao F, Zuo Z, Cai G, Kang S, Gao X. Li T: miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 2009;37(Database issue):D105–10.
Wang D, Yan L, Hu Q, et al. IMA: an R package for high-throughput analysis of Illumina’s 450K Infinium methylation data. Bioinformatics. 2012;28:729–30.
Saeed AI, Sharov V, White J, et al. TM4: a free, open-source system for microarray data management and analysis. BioTechniques. 2003;34:374–8.
Engwerda CR, Handwerger BS, Fox BS. Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol. 1994;152:3740–7.
Linton PJ, Haynes L, Klinman NR, Swain SL. Antigen-independent changes in naïve CD4+ T cells with aging. J Exp Med. 1996;184:1891–900.
Haynes L, Eaton SM, Burns EM, Rincon M, Swain SL. Inflammatory cytokines overcome age-related defects in CD4+ T cell responses in vivo. J Immunol. 2004;172:5194–9.
McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A, Ewen C, Kane KP, Bleackley RC. T cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006;176:6333–9.
Simi A, Ibáñez CF. Assembly and activation of neurotrophic factor receptor complexes. Dev Neurobiol. 2010;70:323–31.
Deng Y, Jing Y, Campbell AE, Gravenstein S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol. 2004;172:3437–46.
Vissinga C, Hertogh-Huijbregts A, Rozing J, Nagelkerken L. Analysis of the age-related decline in alloreactivity of CD4+ and CD8+ T cells in CBA/RIJ mice. Mech Ageing Dev. 1990;51:179–94.
Schmucker DL, Daniels CK, Wang RK, Smith K. Mucosal immune response to cholera toxin in ageing rats. I Antibody and antibody-containing cell response. Immunology. 1988;64:691–5.
Jones SC, Clise-Dwyer K, Huston G, Dibble J, Eaton S, Haynes L, Swain SL. Impact of post-thymic cellular longevity on the development of age-associated CD4+ T cell defects. J Immunol. 2008;180:4465–75.
Blaeser A, Panwar A, Vogel LA. Humoral immunity and aging: intrinsic B cell defects. Curr Trends Immunol. 2007;8:61–7.
Johnson KM, Owen K, Witte PL. Aging and developmental transitions in the B cell lineage. Int Immunol. 2002;14:1313–23.
Zheng B, Han S, Takahashi Y, Kelsoe G. Immunosenescence and germinal center reaction. Immunol Rev. 1997;160:63–77.
Ruffolo RR Jr. Fundamentals of receptor theory: basics for shock research. Circ Shock. 1992;37:176–84.
Hibberd C, Yau JL, Seckl JR. Glucocorticoids and the ageing hippocampus. J Anat. 2000;197(Pt 4):553–62.
Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes. 2012;61:1315–22.
Martin FM, Bydlon G, Friedman JS. SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress. Antioxid Redox Signal. 2006;8:1217–25.
Vaishnaw AK, Toubi E, Ohsako S, Drappa J, Buys S, Estrada J, Sitarz A, Zemel L, Chu JL, Elkon KB. The spectrum of apoptotic defects and clinical manifestations, including systemic lupus erythematosus, in humans with CD95 (Fas/APO-1) mutations. Arthritis Rheum. 1999;42:1833–42.
Chung HY, Lee EK, Choi YJ, et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011;90:830–40.
Ryan KA, Smith MF Jr, Sanders MK, Ernst PB. Reactive oxygen and nitrogen species differentially regulate toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression. Infect Immun. 2004;72(4):2123–30.
Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014;20:648–54. doi:10.1038/nm.3517.
Pérez VI, Bokov A, Van Remmen H, et al. Is the oxidative stress theory of aging dead? Biochim Biophys Acta. 2009;1790:1005–14.
Kuhns DB, Nelson EL, Alvord WG, Gallin JI. Fibrinogen induces IL-8 synthesis in human neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine or leukotriene B(4). J Immunol. 2001;167:2869–78. doi:10.4049/jimmunol.167.5.2869.
Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol. 2001;167:2887–94. doi:10.4049/jimmunol.167.5.2887.
Dostert C, Pétrilli V, van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320:674–7.
Song H, Price PW, Cerny J. Age-related changes in antibody repertoire: contribution from T cells. Immunol Rev. 1997;160:55–62.
Hitchler MJ, Domann FE. An epigenetic perspective on the free radical theory of development. Free Radic Biol Med. 2007;43:1023–36.
Kim C, Kang D, Lee EK, Lee JS. Long noncoding RNAs and RNA-binding proteins in oxidative stress, cellular senescence, and age-related diseases. Oxidative Med Cell Longev. 2017;2017:2062384. https://doi.org/10.1155/2017/2062384. Epub 2017 July 25.
Marshak-Rothstein A, Rifkin IR. Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease. Annu Rev Immunol. 2007;25:419–41. doi:10.1146/annurev.immunol.22.012703.104514.
Blagosklonny MV. Aging: ROS or TOR. Cell Cycle. 2008;7:3344–54.
Levine RL, Stadtman ER. Oxidative modification of proteins during aging. Exper Gerontol. 2001;36:1495–502.
Hawkins S, Wiswell R. Rate and mechanism of maximal oxygen consumption decline with aging: implications for exercise training. Sports Med. 2003;33:877–88.
Campisi J, Andersen JK, Kapahi P, Melov S. Cellular senescence: a link between cancer and age-related degenerative disease? Sem Cancer Biol. 2011;21:354–9.
Tower J. Programmed cell death in aging. Ageing Res Rev. 2015;23:90–100. doi:10.1016/j.arr.2015.04.002. Epub 2015 Apr 8
Goldstein BJ, Mahadev K, Wu X. Redox paradox: insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets. Diabetes. 2005;54:311–21.
Remillard CV, Yuan JX. Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol. 2004;286:L49–67.
Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001;30:1191–212.
Elchuri S, Oberley TD, Qi W, et al. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005;24:367–80.
Croteau DL, Bohr VA. Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem. 1997;272:25409–12.
Melov S, Ravenscroft J, Malik S, et al. Extension of life-span with superoxide dismutase/catalase mimetics. Science. 2000;289:1567–9.
Gehrke N, Mertens C, Zillinger T, Wenzel J, Bald T, Zahn S, et al. Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity. 2013;39:482–95. doi:10.1016/j.immuni.2013.08.004.
Gutscher M, Sobotta MC, Wabnitz GH, et al. Proximity-based protein thiol oxidation by H2O2-scavenging peroxidases. J Biol Chem. 2009;284(46):31532–40.
Bulcao C, Ferreira SR, Giuffrida FM, Ribeiro-Filho FF. The new adipose tissue and adipocytokines. Curr Diabetes Rev. 2006;2:19–28.
Jabaut J, Ckless K. Inflammation, immunity and redox signaling. In: Khatami M, editor. Inflammation, chronic diseases and cancer. Cell and molecular biology, immunology and clinical bases. Rijeka: InTech; 2012. p. 145–60.
Fischetti F, Tedesco F. Cross-talk between the complement system and endothelial cells in physiologic conditions and vascular diseases. Autoimmunity. 2006;39:417–28. doi:10.1080/08916930600739712.
Aprahamian T. Autoimmunity, atherosclerosis and apoptic cell clearance. In: Khatami M, editor. Inflammation, chronic diseases and cancer. Cell and molecular biology, immunology and clinical bases. Rijeka: InTech; 2012. p. 75–96.
Meur YL, Tesch GH, Hill PA, Mu W, Foti R, Nikolic-Paterson DJ, Atkins RC. Monocyte proliferation outside the bone marrow has also been demonstrated in vitro studies using monocytes extracted from peripheral blood and glomeruli. J Leukocyte Biology. 2002;72:530–7.
Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515–96.
Finkelman FD, Shea-Donohue T, Morris SC, Gildea L, Strait R, Madden KB, Schopf L, Urban JF Jr. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol Rev. 2004;201:139–55.
Balkwill F. Cancer and the chemokine network. Nat Rev Cancer. 2004;4:540–50.
Machado ER, Ueta MT, Lourenço EV, Anibal FF, Sorgi CA, Soares EG, et al. Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis. J Immunol. 2005;175:3892–9.
Rossi DJ, Jamieson CH, Weissman IL. Stem cells and the pathways to aging and cancer. Cell. 2008;132:681–96.
Krishnamurthy J, Sharpless NE. Stem cells and the rate of living. Cell Stem Cell. 2007;1:9–11.
Van Zant G, Liang Y. The role of stem cells in aging. Exp Hematol. 2003;31:659–72.
Collins CA, Zammit PS, Ruiz AP, Morgan JE, Partridge TA. A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells. 2007;25:885–94.
Fukada S, Ma Y, Uezumi A. Adult stem cell and mesenchymal progenitor theories of aging. Front Cell Dev Biol. 2014;2:10. doi:10.3389/fcell. 2014.00010. eCollection 2014
Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–84.
Hartman M, Piliponsky AM, Temkin V, Levischaffer F. Human peripheral blood eosinophils express stem cell factor. Blood. 2001;97:1086–91.
Lama VN, Smith L, Badri L, Flint A, Andrei AC, Murray S, et al. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest. 2007;117:989–96.
Biteau B, Jasper H. EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development. 2011;138:1045–55.
Cheung TH, Rando TA. Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol. 2013;14:329–40.
Yuzankina Y, Asare A, Brown EJ. Replicative stress, stem cells and aging. Mech Aging Dev. 2008;129:460–6.
Nishimura EK. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res. 2011;24:401–10.
Nishimura EK, Granter SR, Fisher DE. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science. 2005;307:720–4.
Morikawa S, Mabuchi Y, Niibe K, Suzuki S, Nagoshi N, Sunabori T, et al. Development of mesenchymal stem cells partially originate from the neural crest. Biochem Biophys Res Commun. 2009;379:1114–9.
Brennan TV, Lin L, Huang X, Cardona DM, Li Z, Dredge K, et al. Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD following allogeneic stem cell transplantation. Blood. 2012;120:2899–908. doi:10.1182/blood-2011-07-368720.
Nowarski R, Gagliani N, Huber S, Flavell RA. Innate immune cells in inflammation and cancer. Cancer Immunol Res. 2013;1:77–84. doi:10.1158/2326-6066.CIR-13-0081.
DiCarlo E, Forni G, Lollini PL, Colombo MP, Modesti A, Musiani P. The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood. 2001;97:339–45.
Sigal LJ, Crotty S, Andino R, Rock KL. Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature. 1999;398:77–80.
D’Amico G, Frascaroli G, Bianchi G, Transidico P, Doni A, Vecchi A, Sozzani S, Allavena P, Mantovani A. Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys. Nat Immunol. 2000;1:387–91.
Lloyd CM, Hawrylowicz CM. Regulatory T cells in asthma. Immunity. 2009;31:438–49.
Werling D, Hope JC, Howard CJ, Jungi TW. Differential production of cytokines, reactive oxygen and nitrogen by bovine macrophages and dendritic cells stimulated with toll-like receptor agonists. Immunology. 2004;111:41–52.
Daly C, Dube C, Rollins BJ. Chemokine influences on adaptive immunity and malignancies of the immune system. Emst Schering Res Found Workshop. 2004;45:11–30.
Hadler-Olsen E, Winberg JO, Uhlin-Hansen L. Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol. 2013;34:2041–51.
Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006;33:369–85.
Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22:633–40.
Rajagopalan S. HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction. Cell Mol Immunol. 2014;11:460–6. doi:10.1038/cmi.2014.53. Epub 2014 Jul 7
Cooper MA, Fehniger TA, Fuchs A, Colonna M, Caligiuri MA. NK cell and DC interactions. Trends Immunol. 2004;25:47–52.
Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood. 1990;76:2421–38.
Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986;136:4480–6.
Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R. Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res. 2009;21:201–9.
Lanier LL. NK cell recognition. Annu Rev Immunol. 2005;23:225–74.
Caligiuri MA, Zmuidzinas A, Manley TJ, Levine H, Smith KA, Ritz J. Functional consequences of interleukin 2 receptor expression on resting human lymphocytes: identification of a novel natural killer cell subset with high affinity receptors. J Exp Med. 1990;171:1509–26.
Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, et al. Activation of NK cell cytotoxicity. Mol Immunol. 2005;42:501–10.
Zwirner NW, Fuertes MB, Girart MV, Domaica CI, Rossi LE. Cytokine-driven regulation of NK cell functions in tumor immunity: role of the MICA-NKG2D system. Cytokine Growth Factor Rev. 2007;18:159–70.
Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R, Morelli L, et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med. 1999;190:1505–16.
Balch CM, Tilden AB, Dougherty PA, Cloud GA, Abo T. Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients. Am Surg. 1983;198:192–9.
DiPenta JM, Johnson JG, Murphy RJ. Natural killer cells and exercise training in the elderly: a review. Can J Appl Physiol. 2004;29:419–43.
Shephard RJ, Shek PN. Cancer, immune function, and physical activity. Can J Appl Physiol. 1995;20:1–25.
Haaland DA, Sabljic TF, Baribeau DA, Mukovozov IM, Hart LE. Is regular exercise a friend or foe of the aging immune system? A systematic review. Clin J Sport Med. 2008;18:539–48. doi:10.1097/JSM.0b013e3181865eec.
Albers R, Antoine JM, Bourdet-Sicard R, Calder PC, Gleeson M, Lesourd B, Samartín S, Sanderson IR, Van Loo J, Vas Dias FW, Watzl B. Markers to measure immunomodulation in human nutrition intervention studies. Br J Nutr. 2005;94:452–81.
Ince N, de la Monte SM, Wands JR. Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation. Cancer Res. 2000;60:1261–6.
Perica K, Varela JC, Oelke M, Schneck J. Adoptive T cell immunotherapy for cancer. Rambam Maimonides Med J. 2015;6:e0004. doi:10.5041/RMMJ.10179. eCollection 2015
Gaber T, Strehl C, Sawitzki B, Hoff P, Buttgereit F. Cellular energy metabolism in T-lymphocytes. Intl Rev of Immunol. 2015;34:34–49. doi:10.3109/08830185.2014.956358.
Fulop T Jr, Larbi A, Dupuis G, Pawelec G. Ageing, autoimmunity and arthritis: perturbations of TCR signal transduction pathways with ageing- a biochemical paradigm for the ageing immune system. Arthritis Res Ther. 2003;5:290–302.
Aspinall R. Age-related changes in the function of T cells. Microsc Res Tech. 2003;62:508–13.
Ait-Oufella H, Salomon BL, Potteaux S, Robertson A-KL, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12:178–80.
Zhou X, Nicoletti A, Elhage R, Hansson GK. Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation. 2000;102:2919–22.
Hammad H, Plantinga M, Deswarte K, Pouliot P, Willart MA, Kool M, Muskens F, Lambrecht BN. Inflammatory dendritic cells–not basophils–are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med. 2010;207:2097–111.
Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.
Herrero C, Sebastian C, Marques L, Comalada M, Xaus J, Valledor AF, Lioberas J, Celada A. Immunosenescence of macrophages: reduced MHC class II gene expression. Exp Gerontol. 2002;37:389–94.
Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203:1273–82.
Mckinnon JG, Hoover SK, Inge TH, Bear HD. Activation and expansion of cytotoxic T lymphocytes from tumor-draining lymph nodes. Cancer Immunol Immunother. 1990;32:38–44.
Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 2000;404:407–11.
Hsieh FH, Lam BK, Penrose JF, Austen KF, Boyce JA. T helper cell type 2 cytokines coordinately regulate immunoglobulin E-dependent cysteinyl leukotriene production by human cord blood-derived mast cell: profound induction of leukotriene C(4) synthase expression by interleukin 4. J Exp Med. 2001;193:123–33.
Serelli-Lee V, Ling KL, Ho C, et al. Persistent Helicobacter pylori specific Th17 responses in patients with past H. pylori infection are associated with elevated gastric mucosal IL-1beta. PLoS One. 2012;7(6):e39199.
Fu TM, Ulmer JB, Caulfield MJ, Deck RR, Friedman A, Wang S, Liu X, Donnelly JJ, Liu MA. Priming of cytotoxic T lymphocytes by DNA vaccines: requirement for professional antigen presenting cells and evidence for antigen transfer from myocytes. Mol Med. 1997;3:362–71.
Rafi A, Castle SC, Uyemura K, Makinodan T. Immune dysfunction in the elderly and its reversal by antihistamines. Biomed Pharmacoth. 2003;57:246–50.
Yang K, Chi H. AMPK helps T cell survive nutrient starvation. Immunity. 2015;42:4–6.
Khor SC, Abdul Karim N, Ngah WZ, Yusof YA, Makpol S. Vitamin E in sarcopenia: current evidences on its role in prevention and treatment. Oxidative Med Cell Longev. 2014;2014:914853. doi:10.1155/2014/914853. Epub 2014 Jul 6
Kim J, Wilson JM, Lee S. Dietary implications on mechanisms of sarcopenia: roles of protein, amino acids and antioxidants. J Nutrit Biochem. 2010;21:1–13.
Gashev AA, Chatterjee V. Aged lymphatic contractility: recent answers and new questions. Lymphat Res Biol. 2013;11:2–13.
Choi YS, Baumgarth N. Dual role for B-1a cells in immunity to influenza virus infection. J Exp Med. 2008;205:3053–64.
Matsumura Y, Abe M, Makimura K. Commensal fungi are involved in antigen-specific antibody production in the elderly. Brit J Med Medical Res. 2015;5:1562–70. Article no.BJMMR.2015.176–ISSN: 2231-0614
Perry HM, Bender TP, McNamara CA. B cell subsets in atherosclerosis. Front Immunol. 2012;3:373.
Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520. doi:10.3389/fimmu.2014.00520.
Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, Pennington JE, Wherry JC. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. JAMA. 1995;273:934–41.
Schroeder HW Jr. The evolution and development of the antibody repertoire. Front Immunol. 2015; doi:10.3389/fimmu.2015.00033.
Daugherty A, Puré E, Delfel-Butteiger D, Chen S, Leferovich J, Roselaar SE, Rader DJ. The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E−/− mice. J Clin Invest. 1997;100:1575–80.
Blaeser A, McGlauchlen K, Vogel LA. Aged-B lymphocytes retain their ability to express surface markers but are dysfunctional in their proliferative capability during early activation events. Immun Ageing. 2008;5:15. doi:10.1186/1742-4933-5-15.
Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010;327:291–5. doi:10.1126/science.1183021.
Major AS, Fazio S, Linton MF. B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol. 2002;22:1892–8.
Tsiantoulas D, Diehl CJ, Witztum JL, Christoph J. Binder B cells and humoral immunity in atherosclerosis. Circ Res. 2014;114:1743–56.
Howard WA, Gibson KL, Dunn-Walters DK. Antibody quality in old age. Rejuvenation Res. 2006;9:117–25.
Dailey RW, Eun SY, Russell CE, Vogel LA. B cells of aged mice show decreased expansion in response to antigen, but are normal in effector function. Cell Immunol. 2001;214:99–109.
Neyt K, Perros F, Geurtsvan-Kessel CH, Hammad H, Lambrecht BN. Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol. 2012;33:297–305.
Linterman MA. How T follicular helper cells and the germinal centre response change with age. Immunol Cell Biol. 2014;92:72–9.
Good-Jacobson KL, Shlomchik MJ. Plasticity and heterogeneity in the generation of memory B cells and long-lived plasma cells: the influence of germinal center interactions and dynamics. J Immunol. 2010;185:3117–25. doi:10.4049/jimmunol.1001155.
Tseng CW, Liu GY. Expanding roles of neutrophils in aging hosts. Curr Opin Immunol. 2014;29:43–8.
De Larco JE, Wuertz BRK, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumor releasing interleukin -8. Clin Cancer Res. 2004;10:4895–900.
Jackaman C, Nelson DJ. Are macrophages, myeloid derived suppressor cells and neutrophils mediators of local suppression in healthy and cancerous tissues in aging hosts. Exp Gerontol. 2014;54:53–7.
Teranishi A, Akada S, Saito S, Hatake K, Morikawa H. Macrophage cology-stimulating factor restored chemotherapy-induced granulocyte dysfunction: role of IL-8 production by monocytes. Int Immunopharmacol. 2002;2:83–94.
Rijken F, Bruijzeel-Koomen CA. Photoaged skin: the role of neutrophils, preventive measures and potential pharmacological targets. Clin Pharmacol Ther. 2010;89:120–4.
Gomez-Cambronero J, Kantonen S. A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling. J Leukoc Biol. 2014;96:779–84.
Ohbayashi H, Shimokata K. Matrix metalloproteinase-9 and airway remodeling in asthma. Curr Drug Targets Inflamm Allergy. 2005;4:177–81.
Ibusuki K, Sakiyama T, Kanmura S, Maeda T, Iwashita Y, Nasu Y, Sasaki F, Taguchi H, Hashimoto S, Numata M, Uto H, Tsubouchi H, Ido A. Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2 receptor and ERK1/2 signaling pathways. Int J Mol Med. 2015;35:1603–9. doi:10.3892/ijmm.2015.2156. Epub 2015 Mar 26
Ribatti D, Crivellato E. Mast cell ontology: an historical overview. Immunol Lett. 2014;159:11–4. doi:10.1016/j.imlet.2014.02.003. Epub 2014 Feb 14
Shakoory B, Fitzgerald SM, Lee SA, Chi DS, Krishnawamy G. The role of human mast cell-derived cytokines in eosinophil biology. J Interferon Cytokine Res. 2004;24:271–81.
Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, Asadi S, Vasiadi M, Weng Z, Miniati A, Kalogeromitros D. Mast cells and inflammation. Biochim Biophys Acta. 2012;1822:21–33. doi:10.1016/j.bbadis.2010.12.014.
Valent P, Bettelheim P. Cell surface structures on human basophils and mast cells: biochemical and functional characterization. Adv Immunol. 1992;52:333–423.
Valent P, Schernthaner GH, Sperr WR, Fritsch G, Agis H, Willheim M, Buhring HJ, Orfao A, Escribano L. Variable expression of activation-linked surface antigens on human mast cells in health and disease. Immunol Rev. 2001;179:74–81.
Schwartz LB. The mast cell. In: Kaplan AP, editor. Allergy, vol. 1. Edingurgh: Churchil Livingston; 1985. p. 53–92.
Tomita M, Matsuzaki Y, Onitsuka T. Correlation between mast cells and survival rates in patients with pulmonary adenocarcinoma. Lung Cancer. 1999;26:103–8.
Brightling CE, Bradding P, Pavord ID, Wardlaw AJ. New insights into the role of the mast cell in asthma. Clin Exp Allergy. 2003;33:550–6.
Renauld J-C. New insights into the role of cytokines in asthma. J Clin Pathol. 2001;54:577–89.
Kelley JL, Chi DS, Abou-Auda W, Smith JK, Krishnaswamy G. The molecular role of mast cells in atherosclerotic cardiovascular disease. Mol Med Today. 2000;6:304–8.
Barcante JMP, Barcante TA, Peconick AP, Pereira LJ, Lima WS. Parasitic infections and inflammatory diseases. In: Khatami M, editor. Inflammation, chronic diseases and cancer. Cell and molecular biology, immunology and clinical bases. Rijeka: InTech; 2012. p. 205–18.
Le Meur Y, Tesch GH, Hill PA, Mu W, Foti R, Nikolic-Paterson DJ, Atkins RC. Macrophage accumulation at a site of renal inflammation is dependent on the M-CSF/c-fms pathway. J Leukocyte Biol. 2002;72:530–7.
Lambrecht BN, Hammad H. Death at the airway epithelium in asthma. Cell Res. 2013;23:588–9.
Khatami M, Donnelly JJ, John T, Rockey JH. Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin. Arch Ophthalmol. 1984;102:1683–8.
Khatami M, Donnelly JJ, Rockey JH. Induction and down-regulation of conjunctival type-1 hypersensitivity reactions in guinea pigs sensitized topically with fluoresceinyl ovalbumin. Ophthalmic Res. 1985;17:139–47.
El-Malky M, Maruyama H, Hirabayashi Y, Shimada S, Yoshida A, Amano T, et al. Intraepithelial infiltration of eosinophils and their contribution to the elimination of adult intestinal nematode, Strongyloides venezuelensis in mice. Parasitol Int. 2003;52:71–910.
Austen KF, Boyce JA. Mast cell lineage development and phenotypic regulation. Leuk Res. 2001;25:511–8.
Tobin MJ. Chronic obstructive disease, pollution, pulmonary vascular disease, transplantation, pleural disease, and lung cancer. Am J Respir Crit Care Med. 2000;164:1789.
Galli SJ, Maurer M, Lantz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol. 1999;11:53–9.
Galli SJ. Biology of disease: new insights into ‘the riddle of mast cells’; microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Investig. 1990;62:5–33.
Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011;12:1035–44.
Walls AF, Roberts JA, Godfrey RC, Church MK, Holgate ST. Histochemical heterogeneity of human mast cells: disease-related differences in mast cell subsets recovered by bronchoalveolar lavage. Intl Arch Allergy Appl Immunol. 1990;92:233–41.
Burnet FM. The probable relationship of some or all mast cells to the T-cell system. Cell Immunol. 1977;30:358–60.
Palomares O. The role of regulatory T cells in IgE-mediated food allergy. J Investig Allergol Clin Immunol. 2013;23(6):371–82. quiz 2 p preceding 382
Helleboid L, Khatami M, Wei Z-G, Rockey JH. Histamine and prostacyclin: primary and secondary release in allergic conjunctivitis. Invest Ophthalmol Vis Sci. 1991;32:2281–9.
Rockey JH, Donnelly JJ, John T, Khatami M, Schwartzman RM, Stromberg BE, Bianco AE, Soulsby EJL. IgE antibodies in ocular immunopathology. In: O’Conner GR, Chandler JW, editors. Advances in immunology and immunopathology of the eye. New York: Masson; 1985. p. 199–202.
Ribatti D, Nico B, Ranieri G, Specchia G, Vacca A. The role of angiogenesis in human non-hodgkin lymphomas. Neoplasia. 2013;15:231–8.
Ribati D. The crucial role of mast cells in blood-brain barrier alterations. Exp Cell Res. 2015; doi:10.1016/j.yexcr.2015.05.013. pii: S0014–4827(15)00193–7. [Epub ahead of print]
Ribatti D. Mast cells as therapeutic target in cancer. Eur J Pharmacol. 2015; doi:10.1016/j.ejphar.2015.02.056. pii: S0014-2999(15)00356-8. [Epub ahead of print]
Ribatti D, Ranieri G. Tryptase, a novel angiogenic factor stored in mast cell graules. Exp Cell Res. 2015;332:157–62. doi:10.1016/j.yexcr.2014.11.014. Epub 2014 Dec 3
Vesterinen E, Oukkala E, Timonen T, Aromaa A. Cancer incident among 78000 asmatic patients. Intl J Epidemiol. 1993;22:976–82.
Huovinen E, Kapiro J, Vesterinen E, Koshenvuo M. Mortality of adults with asthma: a prospective cohort study. Thorax. 1997;52:49–54.
Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Onitsuka T. Distribution of mast cells in mediastinal lymph nodes from lung cancer patients. World J Surg Oncol. 2003;1:25.
Khatami M. Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunological challenges in cancer therapy. Clin Cancer Res. 2005;11:1349–51.
Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, Roberts JC, Medhurst AD, Chessell IP. Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain. Pain. 2008;138:61–9. doi:10.1016/j.pain.2007.11.006. Epub 2007 Dec 31
Ammendola M, Marech I, Sammarco G, Zuccalà V, Luposella M, Zizzo N, et al. Infiltrating mast cells correlate with angiogenesis in bone metastases from gastric cancer patients. Int J Mol Sci. 2015;16(2):3237–50. doi:10.3390/ijms160232372015.
Baylin SB, Abeloff MD, Wieman KC, Tomford JW, Ettinger DS. Elevated histaminase (diaminase) activity in small-cell carcinoma of the lung. N Engl J Med. 1975;293:1286–90.
Dvorak A, Seder R, Paul W, Morgan E, Galli S. Effects of interleukin-3 with or without the c-kit ligand, stem cell factor, on the survival and cytoplasmic granule formation of mouse basophils and mast cells in vitro. Am J Pathol. 1994;11:160–70.
Bijanzadeh M, Ramachandra NB, Mahesh PA, Savitha MR, Vijayakumar GS, Kumar P, et al. Soluble intercellular adhesion molecule-1 and E-selectin in patients with asthma exacerbation. Lung. 2009;187:315–20.
Bot I, de Jager SC, Zernecke A, Lindstedt KA, van Berkel TJ, Weber C, Biessen EA. Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice. Circulation. 2007;115:2516–25.
Chatterjee V, Gashev AA. Aging-associated shifts in functional status of mast cells located by adult and aged mesenteric lymphatic vessels. Am J Physiol Heart Circ Physiol. 2012;303:H693–702.
Grimbaldeston MA, Metz M, Yu M, Tsai M, Galli SJ. Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses. Curr Opinion Immunol. 2006;18:751–60.
Gunin AG, Kornilov NK, Vasilieva OV, Petrov VV. Age-related changes in proliferation, the numbers of mast cells, eosinophils, and cd45-positive cells in human dermis. J Gerontol Biol Sci Med Sci. 2011;66:385–92.
Okayama Y, Benyon RC, Rees PH, Lowman MA, Hillier K, Church MK. Inhibition profiles of sodium cromoglycate and nedocromil sodium on mediator release from mast cells of human skin, lung, tonsil, adenoid and intestine. Clin Exp Allergy. 1992;22:401–9.
Gong J, Yang NS, Croft M, Weng IC, Sun L, Liu FT, Chen SS. The antigen presentation function of bone marrow-derived mast cells is spatiotemporally restricted to a subset expressing high levels of cell surface FcepsilonRI and MHC II. BMC Immunol. 2010;11:34. doi:10.1186/1471-2172-11-34.
Cundell DR, Mickle KE. Developing the perfect antihistamine for use in allergic conditions: a voyage in H1 selectivity. eBook, Frontiers in Clinical Drug Research-Anti Allergy Agents. 2016.
Agrawal A, Agrawal S, Gupta S. Dendritic cells in human aging. Exp Gerontol. 2007;42:421–6.
Gosset P, Bureau F, Angeli V, Pichavant M, Faveeuw C, Tonnel AB, Trottein F. Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells. J Immunol. 2003;170:4943–52.
Inaba K, Turley S, Yamaide F, Iyoda T, Mahnke K, Inaba M, et al. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med. 1998;188:2163–73.
Spies B, Hochrein H, Vabulas M, Huster K, Busch DH, Schmitz F, Heit A, Wagner H. Vaccination with plasmid DNA activates dendritic cells via toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice. J Immunol. 2003;171:5908–12.
Khatami M. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society? Clin Trans Med. 2016;5(1):46. Epub 2016 Dec 5
Lambrecht BN, Hammad H. Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Annu Rev Immunol. 2012;30:243–70.
Bobryshev YV. Dendritic cells and their role in atherogenesis. Lab Investig. 2010;90:970–84.
Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I. Activation of lysosomal function during dendritic cell maturation. Science. 2003;299:1400–3.
Uyemura K, Castle SC, Makinodan T. The frail elderly: role of dendritic cells in the susceptibility of infection. Mech Ageing Dev. 2002;123:955–62.
Romagnoli G, Nisini R, Chiani P, Mariotti S, Teloni R, Cassone A, Torosantucci A. The interaction of human dendritic cells with yeast and germ-tube forms of Candida Albicans leads to efficient fungal processing, dendritic cell maturation, and acquisition of a Th1 response-promoting function. J Leukoc Biol. 2004;75:117–26. Epub 2003 Oct 2
Reid SD, Penna G, Adorini L. The control of T cell responses by dendritic cell subsets. Curr Opin Immunol. 2000;12:114–21.
Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med. 2002;195:327–33.
Jonuleit H, Schmitt E, Steinbrink K, Henk AH. Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol. 2001;22:394–400.
Paschen A, Dittmar KE, Grenningloh R, Rohde M, Schadendorf D, Domann E, Chakraborty T, Weiss S. Human dendritic cells infected by Listeria monocytogenes: induction of maturation, requirements for phagolysosomal escape and antigen presentation capacity Eur. J Immunol. 2000;30:3447–56.
Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yhia S, Briere F, Zlotni A, Lebecque S, Caux C. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med. 1998;188:373–86.
Hirsch S, Austyn JM, Gordon S. Expression of the macrophage-specific antigen F4/80 during differentiation of mouse bone marrow cells in culture. J Exp Med. 1981;11:713–25. doi:10.1084/jem.154.3.713.
Sanghera JS, Weinstein SL, Aluwalia M, Girn J, Pelech SL. Activation of multiple proline-directed kinases by bacterial lipopolysaccharide in murine macrophages. J Immunol. 1996;156:4457–65.
Montovani A, Ming WJ, Balotta C, Abdeljalil B, Bottazzi B. Origin and regulation of tumor-associated macrophages: the role of tumor-derived chemotactic factor. Biochim Biophys Acta. 1986;865:59–67.
Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2005;5:953–64. doi:10.1038/nri1733.
Bae YS, Lee JH, Choi SH, Kim S, Almazan F, Witztum JL, Miller YI. Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res. 2009;104:210–8.
Mantovani A, Schioppa T, Biswas SK, Marchesi F, Allavena P, Sica A. Tumor-associated macrophages and dendritic cells as prototypic type II polarized myeloid populations. Tumori. 2003;89(5):459–68.
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.
Fadok VA, de Cathelineau A, Daleke DL, Henson PM, Bratton DL. Loss of phospholipids asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cell by macrophages and fibroblasts. J Biol Chem. 2001;276:1071–7.
Al-Sarireh B, Eremin O. Tumour-associated macrophages (TAMs): disordered function, immune suppression and progressive tumour growth. J R Coll Surg Edinb. 2000;45:1–16.
Stranks AJ, Hansen AL, Panse I, Mortensen M, Ferguson DJP, Puleston DJ, Shenderov K, Watson AS, Veldhoen M, Phadwal K, Cerundolo V, Simon AK. Autophagy controls acquisition of aging features in macrophages. J Innate Immun. 2015;7:375–91. doi:10.1159/000370112.
Weitzman SA, Gordon LI. Inflammation and cancer: role of phagocytic-generated oxidants in carcinogenesis. Blood. 1990;76:655–63.
Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol. 2002;20:395–425.
Zhu L, Zhao Q, Yang T, Ding W, Zhao Y. Cellular metabolism and macrophage functional polarization. Int Rev Immunol. 2015;34:82–100.
Herbeuval JP, Lelievre E, Lambert C, Dy M, Genin C. Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6. J Immunol. 2004;172(7):4630–6.
Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol. 1992;140:301–16.
Barton GM. A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008;118:413–20.
Schumann J. The impact of macrophage membrane lipid composition on innate immune response mechanisms. In: Khatami M, editor. Inflammation, chronic diseases and cancer; cell and molecular biology, immunology and clinical bases. Rijeka: Intech Publishing; 2012. p. 31–52.
Guilliams M, Lambrecht BN, Hammad H. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 2013;6:464–73.
Folkman J. Angiogenesis. Ann Rev Med. 2006;57:1–18.
Wagner DD, Frenette PS. The vessel wall and its interactions. Blood. 2008;111:5271–81.
Saghiri MA, Asatourian A, Orangi J, Sorenson CM, Sheibani N. Functional role of inorganic trace elements in angiogenesis-Part I: N, Fe, Se, P, Au, and Ca. Crit Rev Oncol Hematol. 2015; doi:10.1016/j.critrevonc.2015.05.010. pii: S1040-8428(15)00099-2. [Epub ahead of print]
Benito-Martin A, Di Giannatale A, Ceder S, Peinado H. The new deal: a potential role for secreted vesicles in innate immunity and tumor progression. Front Immunol. 2015;24 doi:10.3389/fimmu.2015.00066.
Oliver G. Lymphatic vasculature development. Nat Rev Immunol. 2004;4:35–45.
Ozerdem U, Stallcup WB. Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis. 2003;6:241–9. doi:10.1023/b:agen.0000021401.58039.a9.
Jackson SP. The growing complexity of platelet aggregation. Blood. 2007;109:5087–95.
Williamson K, Stringer SE, Alexander MY. Endothelial progenitor cells enter the aging arena. Front Physiol. 2012;3:30. doi:10.3389/fphys.2012.00030.
Ribeiro AL, Okamoto OK. Combined effects of pericytes in the tumor microenvironment. Stem Cells Int. 2015;2015:868475.
Liao D, Johnson RS. Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 2007;26:281–90.
Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci. 2008;13:3532–48.
Feuerstein G, Rabinovici R, Leor J, Winkler JD, Vonhof S. Platelet-activating factor and cardiac diseases: therapeutic potential for PAF inhibitors. J Lipid Mediat Cell Signal. 1997;15:255–84.
Cognasse F, Hamzeh H, Chavarin P, Acquart S, Genin C, Garraud O. Evidence of toll-like receptor molecules on human platelets. Immunol Cell Biol. 2005;83:196–8.
Andonegui G, Kerfoot SM, YK MN, Ebbert KV, Patel KD, Kubes P. Platelets express functional toll-like receptor-4. Blood. 2005;106:2417–23.
Fong KP, Barry C, Tran AN, Traxler EA, Wannemacher KM, Tang HY, Speicher KD, Blair IA, Speicher DW, Grosser T, Brass LF. Deciphering the human platelet sheddome. Blood. 2011;117:e15.
Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91:4–15.
Garraud O, Hamzeh-Cognasse H, Cognasse F. Platelets and cytokines: how and why? Transfus Clin Biol. 2012;19:104–8.
Shahabuddin S, Ponath P, Schleimer RP. Migration of eosinophils across endothelial cell monolayers: interactions among IL-5, endothelial-activating cytokines, and C-C chemokines. J Immunol. 2000;164:3847–54.
Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.
Mabeta P, Pepper MS. Hemangiomas – current therapeutic strategies. Int J Dev Biol. 2011;55(4–5):431–7. doi:10.1387/ijdb.103221pm.
Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, et al. Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell. 2012;149:1298–313.
Pathak AP, Hochfeld WE, Goodman SL, Pepper MS. Circulating and imaging markers for angiogenesis. 2008;11:321–35.
Wilson JF. Angiogenesis therapy moves beyond cancer: Ann Intern Med. 2004;141:165–8.
D’Alessio P. Aging and the endothelium. Exp Gerontol. 2004;39:165–71.
Garraud O, Hamzeh-Cognasse H, Pozzetto B, Cavaillon J-M, Cognasse F. Bench-to-bedside review: platelets and active immune functions – new clues for immunopathology? Critical Care. 2013;17:–236. doi:10.1186/cc12716.
Saze Z, Schuler PJ, Hong C-S, Cheng D, Jackson EK, Whiteside TL. Adenosine production by human B cells and B cell-mediated suppression of activated T cells. Blood. 2013;122:9–18.
Deaglio S, Dwyer K, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257–65.
Eltzschig HK, Thompson LF, Karhausen J, Cotta RJ, Ibla JC, Robson SC, et al. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood. 2004;104:3986–92.
Eltzschig HK. Adenosine: an old drug newly discovered. Anesthesiology. 2009;111:904–1510.
Roberts V, Stagg J, Dwyer KM. The role of ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation. Front Immunol. 2014;5:64. eCollection 2014
Karshovska E, Weber C, Von Hundelshausen P. Platelet chemokines in health and disease. Thromb Haemost. 2013;110:894–902.
Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109:1354–8.
Hiratsuka S, Maru Y, Okada A, Seiki M, Noda T, Shibuya M. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res. 2001;61:1207–13.
Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280:C1358–66.
Veale DJ, Maple C. Cell adhesion molecules in rheumatoid arthritis. Drugs Aging. 1996;9:87–92.
Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204–12.
Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269:23757–63.
George J, Goldstein E, Abashidze S, Deutsch V, Shmilovich H, Finkelste A, Herz I, Miller H, Keren G. Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation. Eur Heart J. 2004;25:1003–8.
Harris AL, Zhang H, Moghaddam A, Fox S, Scott P, Pattison A, Gatter K, Stratford L, Bicknell R. Breast cancer angiogenesis- new approaches to therapy via antiangiogenesis, hypoxic activated drugs, and vascular targeting. Breast Cancer Res. 1996;38:97–108.
Napoli C, Ignarro LJ. Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch Pharm Res. 2009;32:1103–8. doi:10.1007/s12272-009-1801-1. Epub 2009.
Napoli C, Hayashi T, Cacciatore F, Casamassimi A, Casini C, Al-Omran M, Ignarro LJ. Endothelial progenitor cells as therapeutic agents in the microcirculation: an update. Atherosclerosis. 2011;215:9–22.
Arnett TR, Gibbons DC, Utting JC, Orriss IR, Hoebertz A, Rosendaal M, Meghji S. Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol. 2003;196:2–8.
Lamoreaux WJ, Fitzgerald ME, Reiner A, Hasty KA, Charles ST. Vascular endothelial growth factor increases release of gelatinase a and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc Res. 1998;55:29–42.
Meldrum DR. Tumor necrosis factor in the heart. Am J Phys. 1998;274:R577–95.
Gille J, Swerlick RA, Lawley TJ, Caughman SW. Differential regulation of vascular cell adhesion molecule-1 gene transcription by tumor necrosis factor alpha and interleukin-1 alpha in dermal microvascular endothelial cells. Blood. 1996;87:211–7.
Lee KH, Lawley TJ, Xu YL, Swerlick RA. VCAM-1-, ELAM-1-, and ICAM-1-independent adhesion of melanoma cells to cultured human dermal microvascular endothelial cells. J Invest Dermatol. 1992;98:79–85.
Zdrojewicz Z, Pachura E, Pachura P. The thymus: a forgotten, but very important organ. Adv Clin Exp Med. 2016;25(2):369–75. doi:10.17219/acem/58802.
Chaudhry MS, Velardi E, Dudakov JA, van den Brink MR. Thymus: the next (re)generation. Immunol Rev. 2016;271(1):56–71. doi:10.1111/imr.12418.
Sepp NT, Gille J, Li LJ, Caughman SW, Lawley TJ, Swerlick RA. A factor in human plasma permits persistent expression of E-selectin by human endothelial cells. J Invest Dermatol. 1994;102:445–50.
Rutkowski MJ, Sughrue ME, Kane AJ, Ahn BJ, Fang S, Parsa AT. The complement cascade as a mediator of tissue growth and regeneration. Inflamm Res. 2010;59:897–905.
LaRocca TJ, Stivison EA, Hod EA, Spitalnik SL, Cowan PJ, Randis TM, Ratner AJ. Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes. MBio. 2014;5:e01251–14.
del Fresno C, Gomez-Garcia L, Caveda L, et al. Nitric oxide activates the expression of IRAK-M via the release of TNF-alpha in human monocytes. Nitric Oxide. 2004;10:213–20.
Weinstein SL, Gold MR, DeFranco AL. Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages. Proc Natl Acad Sci. 1991;88:4148–52.
Hawiger J, Hawiger A, Timmons S. Endotoxin-sensitive membrane component of human platelets. Nature. 1975;256:125–7.
Keaney JF, Hare JM, Balligand JL, Loscalzo J, Smith TW, Colucci WS. Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation. Am J Physiol. 1996;271(Heart Circ. Physiol. 40):H2646–52.
Chen ZS, Pohl J, Lawley TJ, Swerlick RA. Human microvascular endothelial cells adhere to thrombospondin-1 via an RGD/CSVTCG domain independent mechanism. J Invest Dermatol. 1996;106:215–20.
Swerlick RA, Lawley TJ. Role of microvascular endothelial cells in inflammation. J Invest Dermatol. 1993;100:111S–5S.
Olsen KR, Donald JA. Nervous control of circulation: the role of gasotransmitters, NO, CO and H2S. Acta Histochem. 2009;111:244–56.
Giulivi C, Kato K, Cooper CE. Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol. 2006;291:C1225–31.
Taylor CT, Moncada S. Nitric oxide, cytochrome c oxidase, and the cellular response to hypoxia. Arterioscler Thromb Vasc Biol. 2010;30:643–7.
Siddiq A, Aminova LR, Ratan RR. Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress. Neurochem Res. 2007;32:931–46.
Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology. 2009;24:97–106.
Inoue Y, Hatta Y, Takeuchi J, Kosugi S, Miura I. Successful treatment of refractory acute GVHD complicated by severe intestinal transplant-associated thrombotic microangiopathy using recombinant thrombomodulin. Thromb Res. 2011;127:603–4.
Metzen E, Zhou J, Jelkmann W, Fandrey J, Brune B. Nitric oxide impairs normoxic degradation of HIF-1α by inhibition of prolyl hydroxylases. Mol Biol Cell. 2003;14:3470–81.
Li F, Sonveaux P, Rabbani ZN, Liu S, Yan B, Huang Q, Vujaskovic Z, Dewhirst MW, Li C-Y. Regulation of HIF-1α stability through S-nitrosylation. Mol Cell. 2007;26:63–74.
Kim-Shapiro DB, Gladwin MT, Patel RP, Hogg N. The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation. J Inorg Biochem. 2005;99:237–46.
Pierucci M, Galati S, Valentino M, Di Matteo V, Benigno A, Pitruzzella A, Muscat R, Di Giovanni G. Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson’s disease and other motor disorders. CNS Neurol Disord Drug Targets. 2011;10:777–91.
Amento EP, Ehsani N, Palmer H, Libby P. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1991;11:1223–30.
Li L, Moore PK. An overview of the biological significance of endogenous gases: new roles for old molecules. Biochem Soc Trans. 2007;35:1138–41.
Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991;43:109–41.
Meldrum DR, Gambone JC, Morris MA, Esposito K, Giugliano D, Ignarro LJ. Lifestyle and metabolic approaches to maximizing erectile and vascular health. Int J Impot Res. 2012;24:61–8. doi:10.1038/ijir.2011.51. Epub 2011 Nov 10
Fukuto JM, Ignarro LJ. In vivo aspects of nitric oxide (NO) chemistry: does peroxynitrite (−OONO) play a major role in cytotoxicity? Acc Chem Res. 1997;30:149–52.
Pryor WA, Houk KN, Foote CS, Fukuto JM, Ignarro LJ, Squadrito GL, Davies KJA. Free radical biology and medicine, it’s a gas, man. Am J Physiol Regulatory Int Com Physiol. 2006;291:491–511.
Forman HJ, Fukuto J, Torres M. Redox signaling-chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am J Physiol Cell Physiol. 2004;287:C246–56.
Reiter RJ, Tan DX, Qi W, Manchester LC, Karbownik M, Calvo JR. Pharmacology and physiology of melatonin in the reduction of oxidative stress in vivo. Biol Signals Recept. 2000;9:160–71.
Paolocci N, Jackson MI, Lopez BE, Miranda K, Tocchetti CG, Wink DA, Hobbs AJ, Fukuto JM. The pharmacology of nitroxyl (HNO) and its therapeutic potential: not just the janus face of NO. Pharmacol Ther. 2007;113:442–58.
Bickar D, Bonaventura C, Bonaventura J. Carbon monoxide-driven reduction of ferric heme and heme proteins. J Biol Chem. 1984;259:10777–83.
Valentine WN, Toohey JI, Paglia DE, Nakatani M, Brockway RA. Modification of erythrocyte enzyme activities by persulfides and methanethiol: possible regulatory role. Proc Natl Acad Sci U S A. 1987;84:1394–8.
Taoka S, Banerjee R. Characterization of NO binding to human cystathionine β-synthase: possible implications of the effects of CO and NO binding to the human enzyme. J Inorg Biochem. 2001;87:245–51.
Lahoute C, Herbin O, Mallat Z, Tedgui A. Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets. Nat Rev Cardiol. 2011;8:348–58.
Berthet J, Damien P, Hamzeh-Cognasse H, Arthaud CA, Eyraud MA, Zeni F, Pozzetto B, McNicol A, Garraud O, Cognasse F. Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokine secretion. Clin Immunol. 2012;145:189–200.
Hamzeh-Cognasse H, Damien P, Chabert A, Pozzetto B, Cognasse F, Garraud O. Platelets and infections – complex interactions with bacteria. Front Immunol. 2015; doi:10.3389/fimmu.2015.00082.
Garraud O, Hamzeh-Cognasse H, Pozzetto B, Cavaillon JM, Cognasse F. Bench-to-bedside review: platelets and active immune functions – new clues for immunopathology? Crit Care. 2013;17:236. doi:10.1186/cc12716.
Haaland HD, Holmsen H. Potentiation by adrenaline of agonist-induced responses in normal human platelets in vitro. Platelets. 2011;22:328–37.
Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ. Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaII bbeta3 outside-in integrin signaling in human platelets. Blood. 2008;112:2780–6.
Fracchia KM, Walsh CM. Metabolic mysteries of the inflammatory response: T cell polarization and plasticity. Intl Rev of Immunol. 2015;34:3–18.
Gagliani N, Hu B, Huber S, Elinav E, Flavell RA. The fire within: microbes inflame tumors. Cell. 2014;157:776–83. doi:10.1016/j.cell.2014.03.006.
Burnham V, Thornton J. Luteinizing Hormone as a key player in the cognitive decline of Alzheimer’s disease. Horm Behav. 2015; doi:10.1016/j.yhbeh.2015.05.010. pii: S0018-506X(15)00091-4. [Epub ahead of print]
Ferreira ST, Clarke JR, Bomfim TR, De Felice FG. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement. 2014;10(Suppl):S76–83. doi:10.1016/j.jalz.2013.12.010.
Searcy DG, Whitehead JP, Maroney MJ. Interaction of Cu, Zn superoxide dismutase with hydrogen sulfide. Arch Biochem Biophys. 1995;318:251–63.
Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429:417–23.
Smaili SS, Pereira GJ, Costa MM, Rocha KK, Rodrigues L, do Carmo LG, Hirata H, Hsu YT. The role of calcium stores in apoptosis and autophagy. Curr Mol Med. 2013;13:252–65.
Hauser CJ, Sursal T, Rodriguez EK, Appleton PT, Zhang Q, Itagaki K. Mitochondrial damage associated molecular patterns from femoral reamings activate neutrophils through formyl peptide receptors and P44/42 MAP kinase. J Orthop Trauma. 2010;24:534–8. doi:10.1097/BOT.0b013e3181ec4991.
Shirihai OS, Song M, Dorn GW 2nd. How mitochondrial dynamism orchestrates mitophagy. Circ Res. 2015;116:1835–49.
Durcan TM, Fon EA. The three ‘P’s of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 2015;29:989–99.
Dela F, Helge JW. Insulin resistance and mitochondrial function in skeletal muscle. Int J Biochem Cell Biol. 2013;45:11–5.
Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015;14:58–74. doi:10.1038/nrd4467.
Tintignac LA, Brenner HR, Rüegg MA. Mechanisms regulating neuromuscular junction development and function and causes of muscle wasting. Physiol Rev. 2015;95:809–52. doi:10.1152/physrev.00033.2014.
Cruz-Jentoft AJ, Landi F, Schneider SM, Zuniga C, Arai H, Boirie Y, Chen LK, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43:748–59.
Denison HJ, Cooper C, Sayer AA, Robinson SM. Prevention and optimal management of sarcopenia: a review of combined exercise and nutrition interventions to improve muscle outcomes in older people. Clin Interv Aging. 2015;10:859–69. doi:10.2147/CIA.S55842. eCollection 2015
Sayer AA, Dennison EM, Syddall HE, Gilbody HJ, Phillips DI, Cooper C. Type 2 diabetes, muscle strength, and impaired physical function: the tip of the iceberg? Diabetes Care. 2005;28:2541–2.
Batsis JA, Mackenzie TA, Barre LK, Lopez-Jimenez F, Bartels SJ. Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III. Eur J Clin Nutr. 2014;68:1001–7.
Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 2010;8(12):e1000556.
Salminen A, Kaarniranta K, Kauppinen A. Inflammaging disturbed interplay between autophagy and inflammasomes. Aging. 2012;4:166–75.
Oláhová M, Taylor SR, Khazaipoul S, et al. A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Proc Natl Acad Sci. 2008;105:19839–44.
Warburg O. On respiratory impairment in cancer cells. Science. 1956;124:269–70.
Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.
Warburg O. Ueber den stoffwechsel der tumoren. London: Constable; 1930.
Warburg O. Iron, the oxygen-carrier of respiration-ferment. Science. 1925;61:575–82.
Palsson-McDermott EM, O’Neill LAJ. The Warburg effect then and now: from cancer to inflammatory diseases. BioEssays. 2013;35:965–73.
Racker E. Bioenergetics and the problem of tumor growth. Am Sci. 1972;60:56–63.
Lionaki E, Markaki M, Palikaras K, Tavernarakis N. Mitochondria, autophagy and age-associated neurodegenerative diseases: new insights into a complex interplay. Biochim Biophys Acta. 2015; doi:10.1016/j.bbabio.2015.04.010. pii: S0005-2728 (15)00068-7. [Epub ahead of print] Review
Shen HM, Mizushima N. At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy. Trends Biochem Sci. 2014;39:61–71. http://dx.doi.org/10.1016/j.tibs.2013.12.001 24369758
Lu H, Li G, Liu L, Feng L, Wang X, Jin H. Regulation and function of mitophagy in development and cancer. Autophagy. 2013;9:1720–36. doi:10.4161/auto.26550. Epub 2013 Sep 26
Kongara S, Karantza V. The interplay between autophagy and ROS in tumorigenesis. Front Oncol. 2012;2:171. doi:10.3389/fonc.2012.00171. eCollection 2012
Marzetti E, Csiszar A, Dutta D, Balagopal G, Calvani R, Leeuwenburgh C. Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics. Am J Physiol Heart Circ Physiol. 2013;305:H459–76. doi:10.1152/ajpheart.00936.2012. Epub 2013.
Höhn A, Grune T. Lipofuscin: formation, effects and role of macroautophagy. Redox Biol. 2013;11:140–4.
Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Codogno P, Debnath J, Gewirtz DA, Karantza V, Kimmelman A, Kimmelman A, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34:856–80. doi:10.15252/embj.201490784. Epub 2015 Feb 23
Sasaki K, Yoshida H. Organelle autoregulation-stress responses in the ER, Golgi, mitochondria and lysosome. J Biochem. 2015;157:185–95. doi:10.1093/jb/mvv010. Epub 2015 Feb 4
Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK. Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun. 2013;4:2300.
Vessoni AT, Filippi-Chiela EC, Menck CF, Lenz G. Autophagy and genomic integrity. Cell Death Differ. 2013;20:1444–54.
Sridhar S, Botbol Y, Macian F, Cuervo AM. Autophagy and disease: always two sides to a problem. J Pathol. 2012;226:255–73.
Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol. 2009;182:4046–55.
Roberts EW, Deonarine A, Jones JO, Denton AE, Feig C, Lyons SK, et al. Depletion of stromal cells expressing fibroblast activation protein-alpha from skeletal muscle and bone marrow results in cachexia and anemia. J Exp Med. 2013;210:1137–51.
Iverson SL, Orrenius S. The cardiolipin-cytochrome c interaction and the mitochondrial regulation of apoptosis. Arch Biochem Biophys. 2004;423:37–46.
Mangalmurti NS, Chatterjee S, Cheng G, Andersen E, Mohammed A, Siegel DL, Schmidt AM, Albelda SM, Lee JS. Advanced glycation end products on stored red blood cells increase endothelial reactive oxygen species generation through interaction with receptor for advanced glycation end products. Transfusion. 2010;50:2353–61.
Crabtree HG. Observations on the carbohydrate metabolism of tumours. Biochem J. 1929;23(3):536–45.
Krebs H. The Pasteur effect and the relations between respiration and fermentation. Essays Biochem. 1972;8:1–34.
Buchanan BB, Arnon DI. A reverse KREBS cycle in photosynthesis: consensus at last. Photosynth Res. 1990;24:47–53.
Kim JW, Dang CV. Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res. 2006;66:8927–30.
Edens WA, Sharling L, Cheng G, et al. Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J Cell Biol. 2001;154:879–91.
Wang W, Fang H, Groom L, et al. Superoxide flashes in single mitochondria. Cell. 2008;134:279–90.
Kaminskyy V, Zhivotovsky B. Proteases in autophagy. Biochim Biophys Acta. 2012;1824:44–50.
Novikoff AB, Essner E. Cytolysomes and mitochondrial degeneration. J Cell Biol. 1962;15:140–6. http://dx.doi.org/10.1083/jcb.15.1.140 13939127
Young AR, Narita M, Narita M. Cell senescence as both a dynamic and a static phenotype. Methods Mol Biol. 2013;965:1–13. doi:10.1007/978-1-62703-239-1_1.
Ayaz O, Howlett SE. Testosterone modulates cardiac contraction and calcium homeostasis: cellular and molecular mechanisms. Biol Sex Differ. 2015;6:9. doi:10.1186/s13293-015-0027-9. eCollection.
Morimoto RI, Driessen AJ, Hegde RS, Langer T. The life of proteins: the good, the mostly good and the ugly. Nat Struct Mol Biol. 2011;18:1–4. doi:10.1038/nsmb0111-1.
Ycaza Herrera A, Mather M. Actions and interactions of estradiol and glucocorticoids in cognition and the brain: implications for aging women. Neurosci Biobehav Rev. 2015;55:36–52. doi:10.1016/j.neubiorev.2015.04.005.
Halil M, Cemal Kizilarslanoglu M, Emin Kuyumcu M, Yesil Y, Cruz Jentoft AJ. Cognitive aspects of frailty: mechanisms behind the link between frailty and cognitive impairment. J Nutr Health Aging. 2015;19:276–83. doi:10.1007/s12603-014-0535-z.
Plas DR, Thompson CB. Cell metabolism in the regulation of programmed cell death. Trends Endocrinol Metab. 2002;13:75–8.
Meng R, Tang HY, Westfall J, et al. Crosstalk between integrin αvβ3 and estrogen receptor-α is involved in thyroid hormone-induced proliferation in human lung cancer cells. PLoS One. 2011;6:e27547.
De Loof A, Marchal E, Rivera-Perez C, Noriega FG, Schoofs L. Farnesol-like endogenous sesquiterpenoids in vertebrates: the probable but overlooked functional “inbrome” anti-aging counterpart of juvenile hormone of insects? Front Endocrinol. 2015;5(Article 222):1–10.
Davis FB, Lin HY, Shih A, et al. Acting via a cell surface receptor, thyroid hormone is a growth factor for glioma cells. Cancer Res. 2006;66:7270–5.
Farwell AP, Dubord-Tomasetti SA, Pietrzykowski AZ, Stachelek SJ, Leonard JL. Regulation of cerebellar neuronal migration and neurite outgrowth by thyroxine and 3, 3′, 5′-triiodothyronine. Brain Res Dev Brain Res. 2005;154:121–35.
Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. 2014;74:1195–207. doi:10.1007/s40265-014-0259-8.
Cohen K, Ellis M, Khoury S, Davis PJ, Hercbergs A, Ashur-Fabian O. Thyroid hormone is a MAPK-dependent growth factors for human myeloma cells acting via αvβ3 integrin. Mol Cancer Res. 2011;9:1385–94.
Barbieri M, Bonafè M, Franceschi C, Paolisso G. Insulin/IGFI-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab. 2003;285:E1064–71.
Gust DA, Wilson ME, Stocker T, Conrad S, Plotsky PM, Gordon TP. Activity of the hypothalamic-pituitary-adrenal axis is altered by aging and exposure to social stress in female rhesus monkeys. J Clin Endocronol Metab. 2000;85:2556–63.
Attanasio R, Gust DA, Wilson ME, Meeker T, Gordon TP. Immunomodulatory effects of estrogen and progesterone replacement in a nonhuman primate model. J Clin Immunol. 2002;22:263–9.
Kolovou GD, Kolovou V, Mavrogeni S. We are ageing. Biomed Res Int. 2014;808307:2014. doi:10.1155/2014/808307. Epub 2014 Jun 22
Van Poznak CH. Bone health in adults treated with endocrine therapy for early breast or prostate cancer. Am Soc Clin Oncol Educ Book. 2015;35:e567–74. doi:10.14694/EdBook_AM.2015.35.e567.
Lithgow GJ, Miller RA. Determination of aging rate by coordinated resistance to multiple forms of stress. In: Guarente L, Partridge L, Wallace DC, editors. Molecular biology of aging. New York: Cold Spring Harbor Laboratory Press; 2008. p. 427–81.
Kumar V. Innate immune system in sepsis immunopathogenesis and its modulation as a future therapeutic approach. In: Khatami M, editor. Inflammatory diseases; immunopathology, clinical and pharmacological bases. Rijeka: Intech Publishing; 2012. p. 27–56.
Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res Rev. 2011;10:205–15.
Buskirk ER, Hodgson JL. Age and aerobic power: the rate of change in men and women. Fed Proc. 1987;46:1824–9.
Evans MC, Buchanan BB, Arnon DI. A new ferredoxin-dependent carbon reduction cycle in a photosynthetic bacterium. Proc Natl Acad Sci U S A. 1966;55:928–934. , 2001. PMC 224252. doi:10.1073/pnas. 55.4.928.
Kim JW, Dang CV. Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 2005;30:142–50.
Ralser M, Wamelink MM, Kowald A, et al. Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol. 2007;6:article (10).
Kervinen K, Savolainen MJ, Salokannel J, et al. Apolipoprotein E and B polymorphisms—longevity factors assessed in nonagenarians. Atherosclerosis. 1994;105:89–95.
Macauley SH, Stanley M, Caesar EE, Yamada SA, Raichle ME, Perez R, Mahan TM, Sutphen CL, Holtzman DM. Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. J Clin Investig. 2015; doi:10.1172/JCI79742.
Sugden MC, Holness MJ. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003;284:E855–62.
Fitzgerald MD, Tanaka H, Tran ZV, Seals DR. Age-related declines in maximal aerobic capacity in regularly exercising vs. sedentary women: a meta-analysis. J Appl Physiol (1985). 1997;83:160–5.
Amir S, Hartvigsen K, Gonen A, Leibundgut G, Que X, Jensen-Jarolim E, Wagner O, Tsimikas S, Witztum JL, Binder CJ. Peptide mimotopes of malondialdehyde epitopes for clinical applications in cardiovascular disease. J Lipid Res. 2012;53:1316–26.
Newsholme P, de Bittencourt PI Jr. The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease. Curr Opin Clin Nutr Metab Care. 2014;17:295–305.
Edney EB, Gill RW. Evolution of senescence and specific longevity. Nature. 1968;220(5164):281–2.
Warner HR. Superoxide dismutase, aging, and degenerative disease. Free Radic Biol Med. 1994;17:249–58.
Sun Z. Aging, arterial stiffness, and hypertension. Hypertension. 2015;65:252–6.
Paredes SD, Forman KA, García C, Vara E, Escames G, Tresguerres JA. Protective actions of melatonin and growth hormone on the aged cardiovascular system. Horm Mol Biol Clin Investig. 2014;18:79–88.
Williams GM, Mattson MP, et al. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol. 2007;222:122–8.
Cellini E, Nacmias B, Olivieri F, et al. Cholesteryl ester transfer protein (CETP) I405V polymorphism and longevity in Italian centenarians. Mech Ageing Dev. 2005;126:826–8.
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25.
Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 2005;436:660–5.
Milinkovic M, Antin JH, Hergrueter CA, Underhill CB, Sackstein R. CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD. Blood. 2004;103:740–2. doi:10.1182/blood-2003-05-1500.
Bellier A, Chen CS, Kao CY, Cinar HN, Aroian RV. Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathog. 2009;5:e1000689.
Akiyama K, Suzuki H, Grant P, Bing RJ. Oxidation products of nitric oxide, NO2 and NO3, in plasma after experimental myocardial infarction. J Mol Cell Cardiol. 1997;29:1–9.
de la Haba G, Khatami M, Cooper GW, Backlund P, Flaks JG. Alanine or pyruvate is required for the development of myotubes from myoblasts and cortisol satisfies this requirement. Mol Cell Biochem. 1999;198:163–70.
DeLorey DS, Kowalchuk JM, Paterson DH. Effect of age on O(2) uptake kinetics and the adaptation of muscle deoxygenation at the onset of moderate-intensity cycling exercise. J Appl Physiol. 2004;97:165–72.
Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Int Med. 2007;262:509–25.
Vogelpoel LTC, Baeten DLP, de Jong EC, den Dunnen J. Control of cytokine production by human Fc gamma receptors: implications for pathogen defense and autoimmunity. Front Immunol. 2015 Feb 24;6:79. doi: 10.3389/fimmu.2015.00079. eCollection 2015.
Lenton KJ, Therriault H, Cantin AM, Fulop T, Payette H, Wagner JR. Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am J Clin Nutr. 2000;71:1194–200.
Lee YS, Kang YS, Lee JS, Nicolova S, Kim JA. Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apoptotic cell death by capsaicin in Hep G2 human hepatoma cells. Free Radic Res. 2004;38:405–12.
Bianchi ME, Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev. 2007;220:35–46. doi:10.1111/j.1600-065X.2007.00574.x.
Houthoofd K, Braeckman BP, Lenaerts I, et al. Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Exp Gerontol. 2002;37:1371–8.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Khatami, M. (2017). Theories of Aging and Chronic Diseases: Chronic Inflammation an Interdependent ‘Roadmap’ to Age-Associated Illnesses. In: Inflammation, Aging and Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-66475-0_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-66475-0_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-66473-6
Online ISBN: 978-3-319-66475-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)