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Aging and disease    2019, Vol. 10 Issue (2) : 419-428     DOI: 10.14336/AD.2018.0601
Original Article |
The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis
Lucy A. Murtha1,3, Matthew Morten1,3, Michael J. Schuliga2,3, Nishani S. Mabotuwana1,3, Sean A. Hardy1,3, David W. Waters2,3, Janette K. Burgess4,5,6, Doan TM. Ngo2,3, Aaron L. Sverdlov1,3, Darryl A. Knight2,3,7,8,9, Andrew J. Boyle1,3,*
1School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.
2School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
3Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
4University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen and W. J. Kolff Research Institute, The Netherlands.
5Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Glebe, NSW 2037, Australia.
6Discipline of Pharmacology, The University of Sydney, NSW 2006, Australia.
7Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Canada.
8Adjunct Professor, Department of Medicine, University of Western Australia, Australia.
9Research and Innovation Conjoint, Hunter New England Health District, Australia
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Abstract  

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Age-related processes such as senescence, inflammaging, autophagy and mitochondrial dysfunction are interconnected biological processes that diminish the regenerative capacity of the aged heart and lung and have been shown to play a crucial role in cardiac fibrosis and idiopathic pulmonary fibrosis. This review focuses on these four processes of aging in relation to their role in fibrosis. It has long been established that the heart and lung are linked both functionally and anatomically when it comes to health and disease, with an ever-expanding aging population, the incidence of fibrotic disease and therefore the number of fibrosis-related deaths will continue to rise. There are currently no feasible therapies to treat the effects of chronic fibrosis therefore highlighting the importance of exploring the processes of aging and its role in inducing and exacerbating fibrosis of each organ. The focus of this review may help to highlight potential avenues of therapeutic exploration

Keywords Cardiac fibrosis      pulmonary fibrosis      mitochondrial dysfunction      senescence      autophagy      inflammaging      heart      lung      aging     
Corresponding Authors: Boyle Andrew J.   
About author:

These authors contributed equally.

Issue Date: 14 April 2018
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Articles by authors
Lucy A. Murtha
Matthew Morten
Michael J. Schuliga
Nishani S. Mabotuwana
Sean A. Hardy
David W. Waters
Janette K. Burgess
Doan TM. Ngo
Aaron L. Sverdlov
Darryl A. Knight
Andrew J. Boyle
Cite this article:   
Lucy A. Murtha,Matthew Morten,Michael J. Schuliga, et al. The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis[J]. Aging and disease, 2019, 10(2): 419-428.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.0601     OR     http://www.aginganddisease.org/EN/Y2019/V10/I2/419
Figure 1.  Regulation of senescence growth arrest and the senescence-associated secretory phenotype (SASP) in the aging heart and lung

Stresses inducing senescence vary depending on the context, resulting in a variety of effector pathways. However, there is considerable overlap in processing of the stress-response signal and activating effectors of senescence, with a common final outcome, arrest of cell growth.

Figure 2.  Impact of aging on the formation of autolysosome & degradation of contents

Aging increases the cardiomyocyte’s need for autophagy to maintain intracellular homeostasis, but simultaneously reduces the activity of lysosomes and thereby inhibits autophagic flux. The effects of aging on autophagy are opposing in the heat and the lung leading to variable pathological outcomes.

Figure 3.  Alterations in dysfunctional mitochondria in the aging or diseased heart and lung

Reduction in the ability of dysfunctional mitochondria in the heart and lung to create energy causes an energy deficit that disrupts physiological cellular functioning. Mitochondrial dysfunction in the aging heart and may result in the development of mitochondrial cardiomyopathy or IPF respectively. Mitochondrial dysfunction induced by an acute event in the heart significantly disrupts the contraction and relaxation of contractile cells in the heart and perpetuates a cycle of detrimental effect.

[1] Murtha LA, Schuliga MJ, Mabotuwana NS, Hardy SA, Waters DW, Burgess JK, et al. (2017). The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis. Frontiers in Physiology, 8:777.
[2] Friedman SL (2004). Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implications. Nat Clin Pract Gastroenterol Hepatol, 1:98-105.
[3] Wynn TA (2007). Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest, 117:524-529.
[4] Newman AB, Arnold AM, Naydeck BL, Fried LP, Burke GL, Enright P, et al. (2003). "Successful aging": effect of subclinical cardiovascular disease. Arch Intern Med, 163:2315-2322.
[5] Brandenberger C, Muhlfeld C (2016). Mechanisms of lung aging. Cell Tissue Res.
[6] Gazoti Debessa CR, Mesiano Maifrino LB, Rodrigues de Souza R (2001). Age related changes of the collagen network of the human heart. Mech Ageing Dev, 122:1049-1058.
[7] Neilan TG, Coelho-Filho OR, Shah RV, Abbasi SA, Heydari B, Watanabe E, et al. (2013). Myocardial extracellular volume fraction from T1 measurements in healthy volunteers and mice: relationship to aging and cardiac dimensions. JACC Cardiovasc Imaging, 6:672-683.
[8] Chilosi M, Carloni A, Rossi A, Poletti V (2013). Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res, 162:156-173.
[9] Linton PJ, Gurney M, Sengstock D, Mentzer RMJr., Gottlieb RA (2015). This old heart: Cardiac aging and autophagy. J Mol Cell Cardiol, 83:44-54.
[10] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013). The Hallmarks of Aging. Cell, 153:1194-1217.
[11] Shirakabe A, Ikeda Y, Sciarretta S, Zablocki DK, Sadoshima J (2016). Aging and Autophagy in the Heart. Circ Res, 118:1563-1576.
[12] Thannickal VJ (2013). Mechanistic links between aging and lung fibrosis. Biogerontology, 14:609-615.
[13] Boyle AJ, Hwang J, Ye J, Shih H, Jun K, Zhang Y, et al. (2013). The effects of aging on apoptosis following myocardial infarction. Cardiovasc Ther, 31:e102-110.
[14] Huang WT, Akhter H, Jiang C, MacEwen M, Ding Q, Antony V, et al. (2015). Plasminogen activator inhibitor 1, fibroblast apoptosis resistance, and aging-related susceptibility to lung fibrosis. Exp Gerontol, 61:62-75.
[15] Mirzayans R, Andrais B, Scott A, Paterson MC, Murray D (2010). Single-cell analysis of p16(INK4a) and p21(WAF1) expression suggests distinct mechanisms of senescence in normal human and Li-Fraumeni Syndrome fibroblasts. J Cell Physiol, 223:57-67.
[16] Kojima H, Inoue T, Kunimoto H, Nakajima K (2013). IL-6-STAT3 signaling and premature senescence. JAKSTAT, 2:e25763.
[17] West MD, Shay JW, Wright WE, Linskens MH (1996). Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerontol, 31:175-193.
[18] Yanai H, Shteinberg A, Porat Z, Budovsky A, Braiman A, Ziesche R, et al. (2015). Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients. Aging (Albany NY), 7:664-672.
[19] Disayabutr S, Kim EK, Cha SI, Green G, Naikawadi RP, Jones KD, et al. (2016). miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis. PLoS One, 11:e0158367.
[20] Hecker L, Logsdon NJ, Kurundkar D, Kurundkar A, Bernard K, Hock T, et al. (2014). Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med, 6:231ra247.
[21] Ma Y, Chiao YA, Clark R, Flynn ER, Yabluchanskiy A, Ghasemi O, et al. (2015). Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence. Cardiovasc Res, 106:421-431.
[22] Kadowaki S, Shishido T, Sasaki T, Sugai T, Narumi T, Honda Y, et al. (2016). Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion. Int J Mol Sci, 17:542.
[23] Wang C, Jurk D, Maddick M, Nelson G, Martin-Ruiz C, von Zglinicki T (2009). DNA damage response and cellular senescence in tissues of aging mice. Aging Cell, 8:311-323.
[24] Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. (2016). Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature, 530:184-189.
[25] Hashimoto M, Asai A, Kawagishi H, Mikawa R, Iwashita Y, Kanayama K, et al. (2016). Elimination of p19ARF-expressing cells enhances pulmonary function in mice. JCI Insight, 1:e87732.
[26] Xu J, Gonzalez ET, Iyer SS, Mac V, Mora AL, Sutliff RL, et al. (2009). Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice. J Gerontol A Biol Sci Med Sci, 64:731-739.
[27] Reed AL, Tanaka A, Sorescu D, Liu H, Jeong EM, Sturdy M, et al. (2011). Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse. Am J Physiol Heart Circ Physiol, 301:H824-831.
[28] Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ, et al. (2017). Cellular senescence mediates fibrotic pulmonary disease. Nat Commun, 8:14532.
[29] Zhu F, Li Y, Zhang J, Piao C, Liu T, Li HH, et al. (2013). Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial infarction. PLoS One, 8:e74535.
[30] Meyer K, Hodwin B, Ramanujam D, Engelhardt S, Sarikas A (2016). Essential Role for Premature Senescence of Myofibroblasts in Myocardial Fibrosis. J Am Coll Cardiol, 67:2018-2028.
[31] Chiao YA, Ramirez TA, Zamilpa R, Okoronkwo SM, Dai Q, Zhang J, et al. (2012). Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice. Cardiovasc Res, 96:444-455.
[32] Du WW, Li X, Li T, Li H, Khorshidi A, Liu F, et al. (2015). The microRNA miR-17-3p inhibits mouse cardiac fibroblast senescence by targeting Par4. J Cell Sci, 128:293-304.
[33] Watanabe T, Otsu K, Takeda T, Yamaguchi O, Hikoso S, Kashiwase K, et al. (2005). Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death. Biochem Biophys Res Commun, 333:562-567.
[34] Schuliga M, Jaffar J, Harris T, Knight DA, Westall G, Stewart AG (2017). The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF. Sci Rep, 7:41770.
[35] Canan CH, Gokhale NS, Carruthers B, Lafuse WP, Schlesinger LS, Torrelles JB, et al. (2014). Characterization of lung inflammation and its impact on macrophage function in aging. J Leukoc Biol, 96:473-480.
[36] De Lauretis A, Sestini P, Pantelidis P, Hoyles R, Hansell DM, Goh NS, et al. (2013). Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol, 40:435-446.
[37] Moro-Garcia MA, Echeverria A, Galan-Artimez MC, Suarez-Garcia FM, Solano-Jaurrieta JJ, Avanzas-Fernandez P, et al. (2014). Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease. Int J Cardiol, 174:590-599.
[38] Bujak M, Kweon HJ, Chatila K, Li N, Taffet G, Frangogiannis NG (2008). Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction. J Am Coll Cardiol, 51:1384-1392.
[39] Faner R, Rojas M, Macnee W, Agusti A (2012). Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 186:306-313.
[40] Hogaboam CM, Trujillo G, Martinez FJ (2012). Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis. Fibrogenesis Tissue Repair, 5:S3.
[41] Candore G, Aquino A, Balistreri CR, Bulati M, Di Carlo D, Grimaldi MP, et al. (2006). Inflammation, longevity, and cardiovascular diseases: role of polymorphisms of TLR4. Ann N Y Acad Sci, 1067:282-287.
[42] Sun W, Zheng L, Huang L (2012). Role of unusual CD4+ CD28- T cells in acute coronary syndrome. Mol Biol Rep, 39:3337-3342.
[43] Gilani SR, Vuga LJ, Lindell KO, Gibson KF, Xue J, Kaminski N, et al. (2010). CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis. PLoS One, 5:e8959.
[44] Kahloon RA, Xue J, Bhargava A, Csizmadia E, Otterbein L, Kass DJ, et al. (2013). Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med, 187:768-775.
[45] Satta N, Vuilleumier N (2015). Auto-antibodies as possible markers and mediators of ischemic, dilated, and rhythmic cardiopathies. Curr Drug Targets, 16:342-360.
[46] Zhang X-j, Chen S, Huang K-x, Le W-d (2013). Why should autophagic flux be assessed? Acta Pharmacologica Sinica, 34:595-599.
[47] Loos B, du Toit A, Hofmeyr J-HS (2014). Defining and measuring autophagosome flux—concept and reality. Autophagy, 10:2087-2096.
[48] Martinez-Lopez N, Athonvarangkul D, Singh R (2015). Autophagy and aging. Adv Exp Med Biol, 847:73-87.
[49] He LQ, Lu JH, Yue ZY (2013). Autophagy in ageing and ageing-associated diseases. Acta Pharmacol Sin, 34:605-611.
[50] Bejarano E, Cuervo AM (2010). Chaperone-mediated autophagy. Proc Am Thorac Soc, 7:29-39.
[51] Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, et al. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, 441:880-884.
[52] Singh R, Cuervo AM (2011). Autophagy in the cellular energetic balance. Cell Metab, 13:495-504.
[53] Shih H, Lee B, Lee RJ, Boyle AJ (2011). The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol, 57:9-17.
[54] Rezzani R, Stacchiotti A, Rodella LF (2012). Morphological and biochemical studies on aging and autophagy. Ageing Res Rev, 11:10-31.
[55] Mammucari C, Rizzuto R (2010). Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev, 131:536-543.
[56] Araya J, Kojima J, Takasaka N, Ito S, Fujii S, Hara H, et al. (2013). Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 304:L56-69.
[57] Patel AS, Lin L, Geyer A, Haspel JA, An CH, Cao J, et al. (2012). Autophagy in idiopathic pulmonary fibrosis. PLoS One, 7:e41394.
[58] Romero Y, Bueno M, Ramirez R, Alvarez D, Sembrat JC, Goncharova EA, et al. (2016). mTORC1 activation decreases autophagy in aging and idiopathic pulmonary fibrosis and contributes to apoptosis resistance in IPF fibroblasts. Aging Cell.
[59] Sosulski ML, Gongora R, Danchuk S, Dong C, Luo F, Sanchez CG (2015). Deregulation of selective autophagy during aging and pulmonary fibrosis: the role of TGFbeta1. Aging Cell, 14:774-783.
[60] Ghavami S, Cunnington RH, Gupta S, Yeganeh B, Filomeno KL, Freed DH, et al. (2015). Autophagy is a regulator of TGF-beta1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death Dis, 6:e1696.
[61] Gupta SS, Zeglinski MR, Rattan SG, Landry NM, Ghavami S, Wigle JT, et al. (2016). Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac myofibroblasts. Oncotarget, 7:78516-78531.
[62] Hariharan N, Zhai P, Sadoshima J (2011). Oxidative stress stimulates autophagic flux during ischemia/reperfusion. Antioxid Redox Signal, 14:2179-2190.
[63] Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, et al. (2011). Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol, 46:549-559.
[64] Garcia L, Verdejo HE, Kuzmicic J, Zalaquett R, Gonzalez S, Lavandero S, et al. (2012). Impaired cardiac autophagy in patients developing postoperative atrial fibrillation. J Thorac Cardiovasc Surg, 143:451-459.
[65] Payne BAI, Chinnery PF (2015). Mitochondrial dysfunction in aging: Much progress but many unresolved questions. Biochimica et Biophysica Acta, 1847:1347-1353.
[66] Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS (2015). Mitochondrial dysfunction in cardiac aging. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1847:1424-1433.
[67] Scott I, Youle RJ (2010). Mitochondrial fission and fusion. Essays in biochemistry, 47:85-98.
[68] Mora AL, Bueno M, Rojas M (2017). Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J Clin Invest, 127:405-414.
[69] Williams SL, Huang J, Edwards YJK, Ulloa RH, Dillon LM, Prolla TA, et al. (2010). The mtDNA mutation spectrum of the progeroid Polg mutator mouse includes abundant control region multimers. Cell metabolism, 12:675-682.
[70] Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, et al. (2009). Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation, 119:2789-2797.
[71] Khare V, Eckert KA (2002). The proofreading 3′→5′ exonuclease activity of DNA polymerases: a kinetic barrier to translesion DNA synthesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 510:45-54.
[72] Edgar D, Trifunovic A (2009). The mtDNA mutator mouse: Dissecting mitochondrial involvement in aging. Aging (Albany NY), 1:1028-1032.
[73] Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, et al. (2004). Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 429:417-423.
[74] Bueno M, Lai Y-C, Romero Y, Brands J, St. Croix CM, Kamga C, et al. (2015). PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. The Journal of Clinical Investigation, 125:521-538.
[75] Meyers DE, Basha HI, Koenig MK (2013). Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, and Management. Texas Heart Institute Journal, 40:385-394.
[76] Brown DA, Perry JB, Allen ME, Sabbah HN, Stauffer BL, Shaikh SR, et al. (2017). Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol, 14:238-250.
[77] Mann DL, Bristow MR (2005). Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation, 111:2837-2849.
[78] Patel AS, Song JW, Chu SG, Mizumura K, Osorio JC, Shi Y, et al. (2015). Epithelial cell mitochondrial dysfunction and PINK1 are induced by transforming growth factor-beta1 in pulmonary fibrosis. PLoS One, 10:e0121246.
[79] Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, et al. (2017). Extracellular Mitochondrial DNA is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med.
[80] West AP, Shadel GS (2017). Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol, 17:363-375.
[81] Sosulski ML, Gongora R, Feghali-Bostwick C, Lasky JA, Sanchez CG (2017). Sirtuin 3 Deregulation Promotes Pulmonary Fibrosis. The Journals of Gerontology: Series A, 72:595-602.
[82] Paulin R, Dromparis P, Sutendra G, Gurtu V, Zervopoulos S, Bowers L, et al. (2014). Sirtuin 3 Deficiency Is Associated with Inhibited Mitochondrial Function and Pulmonary Arterial Hypertension in Rodents and Humans. Cell Metabolism, 20:827-839.
[83] Chen T, Li J, Liu J, Li N, Wang S, Liu H, et al. (2014). Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway. American Journal of Physiology-Heart and Circulatory Physiology, 308:H424-H434.
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