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Connective Tissue and Age-Related Diseases

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Book cover Biochemistry and Cell Biology of Ageing: Part II Clinical Science

Part of the book series: Subcellular Biochemistry ((SCBI,volume 91))

Abstract

We begin this chapter by describing normal characteristics of several pertinent connective tissue components, and some of the basic changes they undergo with ageing. These alterations are not necessarily tied to any specific disease or disorders, but rather an essential part of the normal ageing process. The general features of age-induced changes, such as skin wrinkles, in selected organs with high content of connective or soft tissues are discussed in the next part of the chapter. This is followed by a section dealing with age-related changes in specific diseases that fall into at least two categories. The first category encompasses common diseases with high prevalence among mostly ageing populations where both genetic and environmental factors play roles. They include but may not be limited to atherosclerosis and coronary heart disease, type II diabetes, osteopenia and osteoporosis, osteoarthritis, tendon dysfunction and injury, age-related disorders of spine and joints. Disorders where genetics plays the primary role in pathogenesis and progression include certain types of progeria, such as Werner syndrome and Hutchinson-Gilford progeria belong to the second category discussed in this chapter. These disorders are characterized by accelerated signs and symptoms of ageing. Other hereditary diseases or syndromes that arise from mutations of genes encoding for components of connective tissue and are less common than diseases included in the first group will be discussed briefly as well, though they may not be directly associated with ageing, but their connective tissue undergoes some changes compatible with ageing. Marfan and Ehlers-Danlos syndromes are primary examples of such disorders. We will probe the role of specific components of connective tissue and extracellular matrix if not in each of the diseases, then at least in the main representatives of these disorders.

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References

  • Alphonsus CS, Rodseth RN (2014) The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia 69:777–784

    Article  CAS  PubMed  Google Scholar 

  • Amano S (2016) Characterization and mechanisms of photoageing-related structures changes in skin. Damages of basement membrane and dermal structure. Exp Dermatol 25:14–19

    Article  CAS  PubMed  Google Scholar 

  • Anderegg U, Simon JC, Averbeck M (2014) More than just a filler – the role of hyaluronan for skin homeostasis. Exp Dermatol 23:295–303

    Article  CAS  PubMed  Google Scholar 

  • Anderson S, Brenner BM (1986) Effects of ageing on the renal glomerulus. Am J Med 80:435–442

    Article  CAS  PubMed  Google Scholar 

  • Asselot-Chapel C, Borchiellini C, Labat-Robert J, Kern P (1996) Expression of laminin and type IV collagen by basement membrane-producing EHS tumours in streptozotocin-induced diabetic mice in vivo modulation by low molecular weight heparin fragments. Biochem Pharmacol 52:1695–1701

    Article  CAS  PubMed  Google Scholar 

  • Avila Rodriguez MI, Rodriguez Barroso LG, Sanchez ML (2018) Collagen: a review on its sources and potential cosmetic applications. J Cosmet Dermatol 17:20–26

    Article  PubMed  Google Scholar 

  • Bargman R, Posham R, Boskey A, Carter E, DiCarlo E, Verdelis K, Raggio C, Pleshko N (2012) High- and low-dose OPG-Fc cause osteopetrosis-like changes in infant mice. Pediatr Res 72:495–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernstein EF, Fisher LW, Li K, LeBaron RG, Tan EM, Uitto J (1995) Differential expression of the versican and decorin genes in photoaged and sun-protected skin. Comparison by immunohistochemical and northern analyses. Lab Investig 72:662–669

    CAS  PubMed  Google Scholar 

  • Birch HL, Peffers MJ, Clegg PD (2016) Influence of ageing on tendon homeostasis. Adv Exp Med Biol 920:247–260

    Article  CAS  PubMed  Google Scholar 

  • Bolignano D, Mattace-Raso F, Sijbrands EJG (2014) The ageing kidney revisited: a systematic review. Ageing Res Rev 14:65–80

    Article  CAS  PubMed  Google Scholar 

  • Bonvetre JV (2014) Maladaptive proximal tubule repair: cell cycle arrest. Nephron Clin Pract 127:61–64

    Article  CAS  Google Scholar 

  • Boos N, Weissbach S, Rohrbach H, Christoph Weiler C, Spratt KF, Nerlich AG (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Phila Pa 1976) 27:2631–2644

    Article  Google Scholar 

  • Boskey AL, Imbert L (2017) Bone quality changes associated with ageing and disease: a review. Ann N Y Acad Sci 1410:93–106

    Article  PubMed  PubMed Central  Google Scholar 

  • Burr DB, Gallant MA (2012) Bone remodelling in osteoarthritis. Nat Rev Rheumatol 8:665–673

    Article  CAS  PubMed  Google Scholar 

  • Bushby KMD, Collins JE, Hicks D (2014) Collagen type VI myopathies. Adv Exp Med Biol 802:185–199

    Article  CAS  PubMed  Google Scholar 

  • Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS (2011) Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest 121:2833–2844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carrino DA, Sorrell JM, Caplan AI (2000) Age-related changes in the proteoglycans of human skin. Arch Biochem Biophys 373:91–101

    Article  CAS  PubMed  Google Scholar 

  • Carrino DA, Onnerfjord P, Sandy JD, Cs-Szabo G, Scott PG, Sorrell JM, Heinegard D, Caplan AI (2003) Age-related changes in the proteoglycans of human skin. Specific cleavage of decorin to yield a major catabolic fragment in adult skin. J Biol Chem 278:17566–17572

    Article  CAS  PubMed  Google Scholar 

  • Carrino DA, Calabro A, Darr AB, Dours-Zimmermann MT, Sandy JD, Zimmermann DR, Sorrell JM, Hascall VC, Caplan AI (2011) Age-related differences in human skin proteoglycans. Glycobiology 21:257–268

    Article  CAS  PubMed  Google Scholar 

  • Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA (2007) Ageinghematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol 5:e201

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Charar C, Gruenbaum Y (2017) Lamins and metabolism. Clin Sci 131:105–111

    Article  Google Scholar 

  • Chawla GS, Agrawal PM, Dhok A (2017) Progeria: an extremely unusual disorder. Skelet Radiol 46:1149–1153

    Article  Google Scholar 

  • Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J (2003) LMNA mutations in atypical Werner’s syndrome. Lancet 362:440–445

    Article  CAS  PubMed  Google Scholar 

  • Chistiakov DA, Sobenin IA, Orekhov AN (2013) Vascular extracellular matrix in atherosclerosis. Cardiol Rev 21:270–288

    Article  PubMed  Google Scholar 

  • Cole MA, Quan T, Voorhees JJ, Fisher GJ (2018) Extracellular matrix regulation of fibroblast function: redefining our perspective on skin ageing. J cell Commun Signal 12:35–43

    Article  PubMed  PubMed Central  Google Scholar 

  • Consortium ADHR (2000) Autosomal dominant hypophosphaetemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348

    Article  CAS  Google Scholar 

  • Cook JR, Ramirez F (2014) Clinical, diagnostic, and therapeutic aspects of the Marfan syndrome. Adv Exp Med Biol 802:77–94

    Article  CAS  PubMed  Google Scholar 

  • Couchourel D, Aubry I, Delalandre A, Lavigne M, Martel-Pelletier J, Pelletier JP, Lajeunesse D (2009) Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production. Arthritis Rheum 60:1438–1450

    Article  PubMed  PubMed Central  Google Scholar 

  • Couppe C, Hansen P, Kongsgaard M, Kovanen V, Suetta C, Aagaard P, Kjaer M, Magnusson SP (2009) Mechanical properties and collagen cross-linking of the patellar tendon in old and young men. J Appl Physiol 107:880–886

    Article  CAS  PubMed  Google Scholar 

  • Cucchiarini M, de Girolamo L, Filardo G, Oliveira M, Orth P, Pape D, Reboul P (2016) Basic science of osteoarthritis. J Exp Orthop 3:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136:729–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding SL, Shen CY (2008) Model of human ageing: recent findings on Werner’s and Hutchinson-Gilford progeria syndromes. Clin Interv Ageing 3:431–444

    Article  CAS  Google Scholar 

  • Ding G, Franki N, Kapasi AA, Reddy K, Gibbons N, Singhal PC (2001) Tubular cell senescence and expression of TGF-beta1 and p21(WAF1/CIP1) in tubulointerstitial fibrosis of ageingrats. Exp Mol Pathol 70:43–53

    Article  CAS  PubMed  Google Scholar 

  • Dipersio JF (2011) Diabetic stem cell “mobilopathy”. N Engl J Med 365:2536–2538

    Article  CAS  PubMed  Google Scholar 

  • Doh YJ, Kim HK, Jung ED, Choi SH, Kim JG, Kim BW, Lee IK (2009) Novel LMNA gene mutation in a patient with atypical Werner’s syndrome. Korean J Intern Med 24:68–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dudhia J, Scott CM, Draper ERC, Heinegaard D, Pitsillides AA, Smith RK (2007) Ageingenhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Ageing Cell 6:547–556

    Article  CAS  Google Scholar 

  • Dyer JM, Miller RA (2018) Chronic skin fragility: current concepts in the pathogenesis, recognition and management of dermatoporosis. J Clin Aesthet Dermatol 11:13–18

    PubMed  PubMed Central  Google Scholar 

  • Eelen G, de Zeeuw P, Simons M, Carmeliet P (2015) Endothelial cell metabolism in normal and diseased vasculature. Circ Res 116:1231–1244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fadini GP, Agostini C, Sartore S, Avogaro S (2007) Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis 194:46–54

    Article  PubMed  Google Scholar 

  • Farr JN, Khosla S (2015) Skeletal changes through the lifespan – from growth to senescence. Nat Rev Endocrinol 11:513–521

    Article  PubMed  PubMed Central  Google Scholar 

  • Favero M, Ramonda R, Goldring MB, Goldring SR, Punzi L (2015) Early knee osteoarthritis. RMD Open 1:e000062

    Google Scholar 

  • Ferguson SJ, Steffen T (2003) Biomechanics of the ageingspine. Eur Spine J 12:S97–S103

    Article  PubMed  PubMed Central  Google Scholar 

  • Gautieri A, Passini FS, Silvan U, Guizar-Sicairos M, Carimati G, Volpi P, Moretti M, Schoenhuber H, Redaelli A, Berli M, Snedeker JG (2017) Advanced glycation end-products: mechanics of aged collagen from molecule to tissue. Matrix Biol 59:95–108

    Article  CAS  PubMed  Google Scholar 

  • Geissler JR, Bajaj D, Fritton JC (2015) American Society of Biomechanics Journal of Biomechanics Award 2013: cortical bone tissue mechanical quality and biological mechanisms possibly underlying atypical fractures. J Biomech 48:883–894

    Article  PubMed  PubMed Central  Google Scholar 

  • Germain DP (2007) Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis 2:32

    Article  PubMed  PubMed Central  Google Scholar 

  • Gillis C, Pool RR, Meagher DM, Stover SM, Reiser K, Willits N (1997) Effect of maturation and ageing on the histomorphometric and biochemical characteristics of equine superficial digital flexor tendon. Am J Vet Res 58:425–430

    CAS  PubMed  Google Scholar 

  • Giunta C, Randolph A, Steinmann B (2005) Mutation analysis of the PLOD1 gene: an efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIa). Mol Genet Metab 86:269–276

    Article  CAS  PubMed  Google Scholar 

  • Goldring MB, Goldring SR (2011) Inflammation in osteoarthritis. Curr Opin Rheumatol 23:471–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland R, Snyder BD, Fligor B, Bishop WR, Statkevich P, Regen A, Sonis A, Riley S, Ploski C, Correia A, Quinn N, Ullrich NJ, Nazarian A, Liang MG, Huh SY, Schwartzman A, Kieran MW (2012) Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 109:16666–16671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grynpass MA, Huckell B, Pritzker KP, Hancock RG, Kessler MJ (1989) Bone mineral and osteoporosis in ageing rhesus monkey. P R Health Sci J 8:197–204

    Google Scholar 

  • Halper J (2010) Growth factors as active participants in carcinogenesis: a perspective. Vet Pathol 47:77–97

    Article  CAS  PubMed  Google Scholar 

  • Halper J (2014) Proteoglycans and diseases of soft tissues. Adv Exp Med Biol 802:49–58

    Article  CAS  PubMed  Google Scholar 

  • Halper J (2018) Basic components of vascular connective tissue and extracellular matrix. Adv Pharmacol 81:95–127

    Article  PubMed  Google Scholar 

  • Halper J, Kjaer M (2014) Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins. Adv Exp Med Biol 802:31–47

    Article  CAS  PubMed  Google Scholar 

  • Harada A, Okuizumi H, Miyagi N, Genda E (1998) Correlation between bone mineral density and intervertebral disc degeneration. Spine (Phila Pa 1976) 23:857–661

    Article  CAS  Google Scholar 

  • Haseeb A, Haqqi TM (2013) Immunopathogenesis of osteoarthritis. Clin Immunol 146:185–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Head T, Daunert S, Goldschmidt-Clermont PJ (2017) The ageing risk and atherosclerosis: a fresh look at arterial homeostasis. Front Genet 8:1–11

    Article  CAS  Google Scholar 

  • Hollander AP, Heathfield TF, Liu JJ, Pidoux I, Roughley PJ, Most JS, Poole AR (1996) Enhanced denaturation of the a1(II) chains of type-II collagen in normal adult human intervertebral discs compared with femoral articular cartilage. J Orthop Res 14:61–66

    Article  CAS  PubMed  Google Scholar 

  • Homandberg GA, Williams JE, Grant D, Schumacher B, Eisenstein R (1985) Heparin-binding fragments are potent inhibitors of endothelial cell growth. Am J Pathol 120:327–332

    CAS  PubMed  PubMed Central  Google Scholar 

  • Homandberg GA, Wen C, Hui F (1998) Cartilage damaging activity of fibronectin fragments derived from cartilage and synovial fluid. Osteoarthr Cartil 6:231–244

    Article  CAS  Google Scholar 

  • Hornebeck W (2003) Down-regulation of tissue inhibitor matrix metalloproteinase-1 (TIMP-1) contributes to matrix degradation and impaired cell growth and survival. Pathol Biol 51:569–573

    Article  CAS  PubMed  Google Scholar 

  • Ingman AM, Ghosh P, Taylor TK (1974) Variation of collagenous and non-collagenous proteins of human knee joint menisci with age and degeneration. Gerontologia 20:212–223

    Article  CAS  PubMed  Google Scholar 

  • Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    Article  CAS  PubMed  Google Scholar 

  • Karra R, Vemullapalli S, Dong C, Herderick EE, Song X, Slosek K, Nevins JR, West M, Goldschmidt-Clermont PJ, Seo D (2005) Molecular evidence for arterial repair in atherosclerosis. Proc Natl Acad Sci U S A 102:16789–16794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaya G, Saurat JH (2007) Dermatoporosis: a chronic cutaneoud insufficiency. Dermatol 215:284–294

    Article  Google Scholar 

  • Kellgren JH, Lawrence JS (1957) Rodiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kielty CM (2006) Elastic fibres in health and disease. Expert Rev Mol Med 8:1–23

    Article  PubMed  Google Scholar 

  • Kielty C, Grant ME (2002) The collagen family: structure, assembly, and organization in the extracellular matrix. In: Royce PM, Steinmann B (eds) Connective tissue and its heritable disorders. Wiley-Liss, New York

    Google Scholar 

  • Kostrominova TY, Brooks SV (2013) Age-related changes in structure and extracellular matrix protein expression levels in rat tendons. Age 35:2203–2214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuro-o, M., Y. Matsumura, H. Aizawa, H. Kawaguchi, T. Suga, T. Utsugi, Y. Ohyama, M. Kurabayashi, T. Kaname, E. Kumek, H. Iwasakik, A. Iida, .T Shiraki-Iida, S. Nishikawa, R. Nagai, and Y. Nabeshima. 1997. Mutation of the mouse klotho gene leads to a syndrome resembling ageing, Nature, 380: 45–51

    Article  Google Scholar 

  • Labat-Robert J (2003) Age-dependent remodeling of connective tissue: role of fibronectin and laminin. Pathol Biol (Paris) 51:563–568

    Article  CAS  Google Scholar 

  • Lamande SR, Bateman JF (2018) Collagen VI disorders: insights on form and function in the extracellular matrix and beyond. Matrix Biol 71–72:348–367

    Article  PubMed  CAS  Google Scholar 

  • Lampropoulos CE, Papaioannou L, D’Cruz DP (2012) Osteoporosis – a risk factor for cardiovascular disease? Nat Rev Rheumatol 8:587–598

    Article  CAS  PubMed  Google Scholar 

  • Langberg H, Rosendal L, Kjaer M (2001) Training-induced changes in peritendinous type I collagen turnover determined by microdialyis in humans. J Physiol 534:297–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lawker RM (1979) Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 73:59–66

    Article  Google Scholar 

  • Le Maitre CL, Freemont AJ, Hoyland JA (2007) Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 9:R45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu XQ, Zhao Y, Gao JG, Pawlyk B, Starcher B, Spencer JA, Yanagisawa H, Zuo J, Li TS (2004) Elastic fibre homeostasis requires lysyl oxidase-like I protein. Nat Genet 36:178–182

    Article  CAS  PubMed  Google Scholar 

  • Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC (2006) Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 355:788–798

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Diez R, Shekhtman A, Ramasamy R, Schmidt AM (2016) Cellular mechanisms and consequences of glycation in atherosclerosis and obesity. Biochim Biophys Acta 1862:2244–2252

    Article  CAS  PubMed  Google Scholar 

  • Lu X, Hu MC (2017) Klotho/FGF23 axis in chronic kidney disease and cardiovascular disease. Kidney Dis 3:15–21

    Article  Google Scholar 

  • Lynch B, Bonod-Bidaud C, Ducourthial G, Affagard JS, Bancelin S, Psilodimitrakopoulos S, Ruggiero F, Allain JM, Schanne-Klein MC (2017) How ageing impacts skin biomechanics: a multiscale study in mice. Sci Rep 7:13750

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Madonna R, Pieragostini D, Balistreri CR, Rossi C, Geng YJ, Del Boccio P, De Caterina R (2018) Diabetic macroangiopathy: pathogenetic insights and novel therapeutic approaches with focus on high glucose-mediated vascular damage. Vasc Pharmacol 107:27–34

    Article  CAS  Google Scholar 

  • Madry H, Luyten FP, Facchini A (2012) Biological aspects of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc 20:407–420

    Article  PubMed  Google Scholar 

  • Malfait F, De Paepe A (2014) The Ehlers-Danlos syndrome. Adv Exp Med Biol 802:129–143

    Article  CAS  PubMed  Google Scholar 

  • Marini JC, Blissett AR (2013) New genes in bone development: what’s new in osteogenesis imperfecta. J Clin Endocrinol Metab 98:3095–3103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maytin EV (2016) Hyaluronan: more than just a wrinkle filler. Glycobiology 26:553–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McAlinden A, Dudhia J, Bolton MC, Lorenzo P, Heinegaard D, Bayliss MT (2001) Age-related changes in the synthesis and mRNA expression of decorin and aggrecan in human meniscus and articular cartilage. Osteoarthr Cartil 9:33–41

    Article  CAS  Google Scholar 

  • Meester J, Verstraeten A, Schepers D, Alaerts M, Van Laer L, Loeys BL (2017) Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg 6:582–594

    Article  PubMed  PubMed Central  Google Scholar 

  • Melk A, Schmidt BMW, Takeuchi O, Sawitzki B, Rayner DC, Halloran PF (2004) Expression of p16INK4a and other cell cycle regulator and senescence associated genes in ageinghuman kidney. Kidney Int 65:510–520

    Article  CAS  PubMed  Google Scholar 

  • Melrose J, Smith S, Cake M, Read R, Whitelock J (2005) Comparative spatial and temporal location of perlecan, aggrecan, and type I, II, and IV collagen in the ovine meniscus: an ageing study. Histochem Cell Biol 124:225–235

    Article  CAS  PubMed  Google Scholar 

  • Mienaltowski MJ, Birk DE (2014) Structure, physiology, and biochemistry of collagens. Adv Exp Med Biol 802:5–29

    Article  CAS  PubMed  Google Scholar 

  • Miyake N, Kosho T, Matsumoto N (2014) Ehlers-Danlos syndrome associated with glycosaminoglycan abnormalities. Adv Exp Med Biol 802:145–159

    Article  CAS  PubMed  Google Scholar 

  • Moiseeva O, Lessard F, Acevedo-Aquino M, Vernier M, Tsantrizos YS, Ferbeyre G (2015) Mutant lamin A links prophase to a p53 independent senescence program. Cell Cycle 14:2408–2421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mounkes LC, Stewart CL (2004) Ageing and nuclear organization: lamins and progeria. Curr Opin Cell Biol 16:322–327

    Article  CAS  PubMed  Google Scholar 

  • Muiznieks LD, Weiss AS, Keeley FW (2010) Structural disorder and dynamics of elastin. Biochem Cell Biol 88:239–250

    Article  CAS  PubMed  Google Scholar 

  • Munoz-Espin D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15:482–496

    Article  CAS  PubMed  Google Scholar 

  • Musso CG, Oreopoulos DG (2011) Ageing and physiological changes of the kidneys including changes in glomerular filtration rate. Nephron Physiol 119(Suppl 1):1–5

    Article  CAS  Google Scholar 

  • O’Sullivan ED, Hughes J, Ferenbach DA (2017) Renal ageing: causes and consequences. J Am Soc Nephrol 28:407–420

    Article  PubMed  Google Scholar 

  • Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB (2010) Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of ageing. Arteriosc Throm Vasc Biol 30:2301–2309

    Article  CAS  Google Scholar 

  • Oshimo J, Sidorova JM, Monnat RJJ (2017) Werner syndrome: clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev 33:105–114

    Article  CAS  Google Scholar 

  • Paloian NJ, Giachelli CM (2014) A current understanding of vascular calcification in CKD. Am J Physiol Renal Physiol 307:F891–F900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parkinson J, Samiric T, Ilic MZ, Cook J, Handley CJ (2011) Involvement of proteoglycans in tendinopathy. J Musculoskelet Neuronal Interact 11:86–93

    CAS  PubMed  Google Scholar 

  • Pauli C, Grogan SP, Patil S, Otsuki S, Hasegawa A, Koziol J, Lotz MK, D’Lima DD (2011) Macroscopic and histopathologic analysis of human knee menisci in ageing and osteoarthritis. Osteoarthr Cartil 19:1132–1141

    Article  CAS  Google Scholar 

  • Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395

    Article  CAS  PubMed  Google Scholar 

  • Quentin E, Gladen A, Rodén L, Kresse H (1990) A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyl-transferase I deficiency in fibroblasts from a patient with progeroid syndrome. Proc Natl Acad Sci U S A 87:1342–1346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raggi P, Callister TQ, Lippolis MJ, Russo DJ (2000) Is mitral valve prolapse due to cardiac entrapment in the chest cavity? A CT view. Chest 117:636–642

    Article  CAS  PubMed  Google Scholar 

  • Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Ageing, progenitor cells exhaustion, and atherosclerosis. Circulation 108:457–463

    Article  PubMed  Google Scholar 

  • Reed CC, Iozzo RV (2003) The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconjug J 19:249–255

    Article  Google Scholar 

  • Ricard-Blum S, Baffet G, Theret N (2018) Molecular and tissue alterations of collagens in fibrosis. Matrix Biol 68–69:122–149

    Article  PubMed  CAS  Google Scholar 

  • Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ 3rd (1981) Differential changes in bone mineral density of the appendicular and axial skeleton with ageing: relationship to spinal osteoporosis. J Clin Invest 67:328–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL (1994) Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis 53:367–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robert L, Labat-Robert J (2000) Ageing of connective tissues: from genetic to epigenetic mechanisms. Biogerontology 1:123–131

    Article  CAS  PubMed  Google Scholar 

  • Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J (2016) Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 12:580–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodríguez JP, Montecinos L, Ríos S, Reyes P, Martínez J (2000) Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation. J Cell Biochem 79:557–565

    Article  PubMed  Google Scholar 

  • Rork JF, Huang JT, Gordon LB, Kleinman M, Kieran MW, Liang MG (2014) Initial cutaneous manifestations of Hutchinson-Gilford progeria syndrome. Pediatr Dermatol 31:196–202

    Article  PubMed  PubMed Central  Google Scholar 

  • Roughley PJ (2004) Biology of intervertebral disc ageing and degeneration: involvement of the extracellular matrix. Spine (Phila Pa 1976) 29:2691–2699

    Article  Google Scholar 

  • Roughley PJ, Alini MAJ (2002) The role of proteoglycans in ageing, degeneration and repair of the intervertebral disc. Biochem Soc Trans 30:869–874

    Article  CAS  PubMed  Google Scholar 

  • Roughley PJ, White RJ, Magny MC, Liu JH, Pearce RH, Mort JS (1993) Non-proteoglycan forms of biglycan increase with age in human articular cartilage. Biochem J 295:421–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudijanto A (2007) The role of vascular smooth muscle cells in the pathogenesis of atherosclerosis. Acta Med Indones 39:86–93

    PubMed  Google Scholar 

  • Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in ageing, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214

    Article  CAS  PubMed  Google Scholar 

  • Saito I, Koshino T, Nakashima K, Uesugi M, Saito T (2002) Increased cellular infiltrate in inflammatory synovia of osteoarthritic knees. Osteoarthr Cartil 10:156–162

    Article  CAS  Google Scholar 

  • Samiric T, Ilic MZ, Handley CJ (2004) Characterization of proteoglycans and their catabolic products in tendons and explant cultures of tendon. Matrix Biol 23:127–140

    Article  CAS  PubMed  Google Scholar 

  • Sarkar PK, Shinto RA (2001) Hutchinson-Guilford progeria syndrome. Postgrad Med J 77:312–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaefer L, Iozzo RV (2008) Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem 283:21305–21309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schafer MJ, Haak MJ, Tschumperlin DJ, LeBrasseur NK (2018) Targeting senescent cells in fibrosis: pathology, paradox, and practical considerations. Curr Rheum Rep 20:3

    Article  Google Scholar 

  • Schmidt AM (2015) Soluble RAGEs – prospects for treating and tracking metabolic and inflammatory disease. Vasc Pharmacol 72:1–8

    Article  CAS  Google Scholar 

  • Scott A, Lian O, Roberts CR, Cook JL, Handley CJ, Bahr R, Samiric T, Ilic MZ, Parkinson J, Hart DA, Duronio V, Khan KM (2007) Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper’s knee. Scand J Med Sci Sports 8:427–435

    Article  Google Scholar 

  • Seidler DG, Faiyaz-Ul-Haque M, Hansen U, Yip GW, Zaidi SHE, Teebi AS, Kiesel L, Götte M (2006) Defective glycosylation of decorin and biglycan, altered collagen stucture, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (β4GalT-7). J Mol Med 84:583–594

    Article  CAS  PubMed  Google Scholar 

  • Sharpless NE, Sherr CJ (2015) Forging a signature of in vivo senescence. Nat Rev Cancer 15:397–408

    Article  CAS  PubMed  Google Scholar 

  • Shimizu H, Nakagami H, Morishita R (2014) Bone metabolism and cardiovascular function update. Cross link of hypertension, bone loss and vascular calcification – common backgrounds in renin angiotensin system with anti-ageing aspect. Clin Calcium 24:53–62

    PubMed  Google Scholar 

  • Sivan SS, Tsitron E, Wachtel E, Roughley P, Sakkee N, van der Ham F, Degroot J, Maroudas A (2006) Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs. Biochem J 399:29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smeets B, Uhlig S, Fuss A, Mooren F, Wetzels JF, Floege J, Moeller MJ (2009) Tracing the origin of glomerular extracapillary lesions from parietal epithelial cells. J Am Soc Nephrol 20:2604–2615

    Article  PubMed  PubMed Central  Google Scholar 

  • Steffes MW, Schmidt D, McCrery R, Basgen JM (2001) Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int 59:2104–2113

    Article  CAS  PubMed  Google Scholar 

  • Stehbens WE, Wakefield SJ, Gilbert-Barness E, Olson RE, Ackerman J (1999) Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol 8:29–39

    Article  CAS  PubMed  Google Scholar 

  • Ström Å, Ahlqvist E, Franzén A, Heinegård D, Hultgårdh-Nilsson A (2004) Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: an immunohistochemical study. Histol Histopathol 19:337–347

    PubMed  Google Scholar 

  • Svensson RB, Smith ST, Moyer PJ, Magnusson SP (2018) Effects of maturation and advanced glycation on tensile mechanics of collagen fibrils from rat tail and Achilles tendons. Acta Biomater 70:270–280

    Article  CAS  PubMed  Google Scholar 

  • Sztrolovics R, Alini M, Roughley PJ, Mort JS (1997) Aggrecan degradation in human intervertebral disc and articular cartilage. Biochem J 326:235–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tariq Z, Zhang H, Chia-Liu A, Shen Y, Gete Y, Xiong ZM, Tocheny C, Campanello L, Wu D, Losert W, Cao K (2017) Lamin A and microtubules collaborate to maintain nuclear morphology. Nucleus 8:433–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tesauro M, Mauriello A, Rovella V, Annicchiarico-Petruzzelli M, Cardillo C, Melino G, Di Daniele N (2017) Arterial ageing: from endothelial dysfunction to vascular calcification. J Intern Med 281:471–482

    Article  CAS  PubMed  Google Scholar 

  • Tian Y, Yuan W, Fujita N, Wang J, Shapiro IM, Risbud MV (2013) Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB. Am J Pathol 182:2310–2321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsao CW, Pencina KM, Massaro JM, Benjamin EJ, Levy D, Vasan RS, Hoffmann U, O’Donnell CJ, Mitchell GF (2014) Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification. Arterioscler Thromb Vasc Biol 34:2495–2500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsujii A, Nakamura N, Horibe S (2017) Age-related changes in the knee meniscus. Knee 24:1262–1270

    Article  PubMed  Google Scholar 

  • Tu Y, Sánchez-Iglesias S, Araújo-Vilar D, Fong LG, Young SG (2016) LMNA missense mutations causing familial partial lipodystrophy do not lead to an accumulation of prelamin A. Nucleus 7:512–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valentijn FA, Falke LL, Nguyen TQ, Goldschmeding R (2017) Cellular senescence in the ageing and diseased kidney. J Cell Commun Signal 12:69–82

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Laer L, Dietz H, Loeys B (2014) Loeys-Dietz syndrome. Adv Exp Med Biol 802:95–105

    Article  PubMed  CAS  Google Scholar 

  • Varani J, Dame MK, Rittie L, Fligiel SE, Kang S, Fisher GJ, Voorhees JJ (2006) Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol 168(6):1861–1868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vidak S, Foisner R (2016) Molecular insights into the premature ageing disease progeria. Histochem Cell Biol 145:401–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viguet-Carrin S, Garmero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336

    Article  CAS  PubMed  Google Scholar 

  • Vo NV, Hartman RA, Patil PR, Risbud MV, Kletsas D, Iatridis JC, Hoyland JA, Le Maitre CL, Sowa GA, Kang JD (2016) Molecular mechanisms of biological ageing in intervertebral discs. J Orthop Res 34:1289–12306

    Article  PubMed  PubMed Central  Google Scholar 

  • Vogel KG, Sandy JD, Pogany G, Robbins JR (1994) Aggrecan in bovine tendon. Matrix Biol 14:171–179

    Article  CAS  PubMed  Google Scholar 

  • Wagenseil JE, Mecham RP (2012) Elastin in large artery stiffness and hypertension. J Cardiovasc Transl Res 5:264–273

    Article  PubMed  PubMed Central  Google Scholar 

  • Waller JM, Malbach HI (2005) Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol 11:221–235

    Article  PubMed  Google Scholar 

  • Wheeler JB, Ikonomidis JS, Jones JA (2014) Connective tissue disorders and cardiovascular complications: the indomitable role of transforming growth factor-beta signalling. Adv Exp Med Biol 802:107–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wight TN, Kang I, Merrilees MJ (2014) Versican and the control of inflammation. Matrix Biol 35:152–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu YJ, La Pierre DP, Wu J, Yee AJ, Yang BB (2005) The interaction of versican with its binding partners. Cell Res 15:483–494

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Qiang M, Bin X, Liu G, Zhao J (2014) Expression of matrix metalloproteinases is positively related to the severity of disc degeneration and growing age in the East Asian lumbar disc herniation patients. Cell Biochem Biophys 70:1219–1225

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV (2010) Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med 16:535–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasui T, Yonetsu M, Tanaka R, Tanaka Y, Fukushima S, Yamashita T, Ogura Y, Hirao T, Murota H, Araki T (2013) In vivo observation of agerelated structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser. J Biomed Opt 18:31108

    Article  PubMed  CAS  Google Scholar 

  • Yeowell HN, Walker LC, Neumann LM (2005) An Ehlers-Danlos syndrome type VIA patient with cystic malformation of the meninges. Eur J Dermatol 15:353–358

    CAS  PubMed  Google Scholar 

  • Yoon JH, Halper J (2005) Tendon proteoglycans: biochemistry and function. J Musculoskelet Neuronal Interact 5:22–34

    CAS  PubMed  Google Scholar 

  • Young MF (2003) Bone matrix proteins: their function, regulation, and relationship to osteoporosis. Osteoporos Int 14:535–542

    Article  CAS  Google Scholar 

  • Zeng Y, Wu J, He X, Li L, Liu X, Liu X (2017) Mechanical microenvironment regulation of age-related disease involving degeneration of human skeletal and cardiovascular systems. Prog Biophys Mol Biol. https://doi.org/10.1016/j.pbiomolbio.2017.09.022. (in press)

  • Zhang J, Wang JH (2010) Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord 11:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang J, Wang HC (2015) Moderate exercise mitigates the detrimental effects on tendon stem cells. PLoS One 10(6):e0130454

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang G, Ezura Y, Chervoneva I, Robinson PS, Beason DP, Carine ET, Soslowsky LJ, Iozzo RV, Birk DE (2006) Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J Cell Biochem 98:1436–1449

    Article  CAS  PubMed  Google Scholar 

  • Zhang YN, Xie BD, Sun L, Chen W, Jiang SL, Liu W, Bian F, Tian H, Li RK (2016) Phenotypic switching of vascular smooth muscle cells in the ‘normal region’ of aorta from atherosclerosis patients is regulated by miR-145. J Cell Mol Med 20:1049–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao CQ, Zhang YH, Jiang SD, Li H, Jiang LS, Dai LY (2011) ADAMTS-5 and intervertebral disc degeneration: the results of tissue immunohistochemistry and in vitro cell culture. J Orthop Res 29:718–725

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann DR, Dours-Zimmermann MT, Schubert M, Bruckner-Tuderman L (1994) Versican is expressed in the proliferating zone of the epidermis and in association with the elastic network of the dermis. J Cell Biol 124:817–825

    Article  CAS  PubMed  Google Scholar 

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Sarbacher, C.A., Halper, J.T. (2019). Connective Tissue and Age-Related Diseases. In: Harris, J., Korolchuk, V. (eds) Biochemistry and Cell Biology of Ageing: Part II Clinical Science. Subcellular Biochemistry, vol 91. Springer, Singapore. https://doi.org/10.1007/978-981-13-3681-2_11

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