Skip to main content

Advertisement

SpringerLink
Log in

Cardiac aging and heart disease in humans

  • Review
  • Published:
Biophysical Reviews Aims and scope Submit manuscript

Abstract

The world population continues to grow older rapidly, mostly because of declining fertility and increasing longevity. Since age represents the largest risk factor for cardiovascular disease, the prevalence of these pathologies increases dramatically with increasing age. In order to improve patient care and prevention for age-related cardiac diseases, insight should be gained from the analysis of processes involved in and leading to cardiac aging. It is from this perspective that we provide here an overview of changes associated with age in the heart on four levels: functional, structural, cellular and molecular. We highlight those changes that are in common with the development of the two major age-associated cardiac pathologies: heart failure and atrial fibrillation. These commonly affected processes in aging and cardiac pathophysiology may provide an explanation for the age risk factor in cardiac disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Akasheva DU, Plokhova EV, Tkacheva ON, Strazhesko ID, Dudinskaya EN, Kruglikova AS, Pykhtina VS, Brailova NV, Pokshubina IA, Sharashkina NV, Agaltsov MV, Skvortsov D, Boytsov SA (2015) Age-related left ventricular changes and their association with leukocyte telomere length in healthy people. PLoS ONE 10:e0135883

    Article  PubMed  PubMed Central  Google Scholar 

  • Babusikova E, Lehotsky J, Dobrota D, Racay P, Kaplan P (2012) Age-associated changes in Ca(2+)-ATPase and oxidative damage in sarcoplasmic reticulum of rat heart. Physiol Res 61:453–460

    CAS  PubMed  Google Scholar 

  • Bhuiyan ZA, Van den Berg MP, van Tintelen JP, Bink-Boelkens MT, Wiesfeld AC, Alders M, Postma AV, van Langen I, Mannens MM, Wilde AA (2007) Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features. Circulation 116:1569–1576

    Article  PubMed  Google Scholar 

  • Braunwald E (1997) Shattuck lecture--cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 337:1360–1369

    Article  CAS  PubMed  Google Scholar 

  • Braunwald E (2015) The war against heart failure: the lancet lecture. Lancet 385:812–824

    Article  PubMed  Google Scholar 

  • Burstein B, Nattel S (2008) Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 51:802–809

    Article  CAS  PubMed  Google Scholar 

  • Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima JA (2009) Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging 2:191–198

    Article  PubMed  PubMed Central  Google Scholar 

  • Chiao YA, Rabinovitch PS (2015) The aging heart. Cold Spring Harb Perspect Med 5:a025148

    Article  PubMed  Google Scholar 

  • Chung CM, Connors LH, Benson MD, Walsh MT (2001) Biophysical analysis of normal transthyretin: implications for fibril formation in senile systemic amyloidosis. Amyloid 8:75–83

    Article  CAS  PubMed  Google Scholar 

  • Dai DF, Chen T, Johnson SC, Szeto H, Rabinovitch PS (2012) Cardiac aging: from molecular mechanisms to significance in human health and disease. Antioxid Redox Signal 16:1492–1526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Desai A, Fang JC (2008) Heart failure with preserved ejection fraction: hypertension, diabetes, obesity/sleep apnea, and hypertrophic and infiltrative cardiomyopathy. Heart Fail Clin 4:87–97

    Article  PubMed  Google Scholar 

  • Di PA, Caruso E, Costanzo L, Guccione P (2014) A novel RyR2 mutation in a 2-year-old baby presenting with atrial fibrillation, atrial flutter, and atrial ectopic tachycardia. Heart Rhythm 11:1480–1483

    Article  Google Scholar 

  • Dzeshka MS, Lip GY, Snezhitskiy V, Shantsila E (2015) Cardiac fibrosis in patients with atrial fibrillation: mechanisms and clinical implications. J Am Coll Cardiol 66:943–959

    Article  PubMed  Google Scholar 

  • Emdin M, Fatini C, Mirizzi G, Poletti R, Borrelli C, Prontera C, Latini R, Passino C, Clerico A, Vergaro G (2015) Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible? Clin Chim Acta 443:85–93

    Article  CAS  PubMed  Google Scholar 

  • Falk RH (2012) Senile systemic amyloidosis: are regional differences real or do they reflect different diagnostic suspicion and use of techniques? Amyloid 19(Suppl 1):68–70

    Article  PubMed  Google Scholar 

  • Feridooni HA, Dibb KM, Howlett SE (2015) How cardiomyocyte excitation, calcium release and contraction become altered with age. J Mol Cell Cardiol 83:62–72

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N, Komici K, Corbi G, Pagano G, Furgi G, Rengo C, Femminella GD, Leosco D, Bonaduce D (2014) Beta-adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol 4:396

    Article  PubMed  PubMed Central  Google Scholar 

  • Gazoti Debessa CR, Mesiano Maifrino LB, de Rodrigues SR (2001) Age related changes of the collagen network of the human heart. Mech Ageing Dev 122:1049–1058

    Article  CAS  PubMed  Google Scholar 

  • Gregoratos G (1999) Permanent pacemakers in older persons. J Am Geriatr Soc 47:1125–1135

    Article  CAS  PubMed  Google Scholar 

  • Iravanian S, Dudley SC Jr (2008) The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias. Heart Rhythm 5:S12–S17

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones SA (2006) Ageing to arrhythmias: conundrums of connections in the ageing heart. J Pharm Pharmacol 58:1571–1576

    Article  CAS  PubMed  Google Scholar 

  • Katz AM, Rolett EL (2016) Heart failure: when form fails to follow function. Eur Heart J 37:449–454

    Article  PubMed  Google Scholar 

  • Keller KM, Howlett SE (2016) Sex differences in the biology and pathology of the aging heart. Can J Cardiol 32:1065–1073

    Article  PubMed  Google Scholar 

  • Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart disease. Circulation 107:346–354

    Article  PubMed  Google Scholar 

  • Lakatta EG, Sollott SJ (2002) Perspectives on mammalian cardiovascular aging: humans to molecules. Comp Biochem Physiol A 132:699–721

    Article  Google Scholar 

  • Lam CS, Donal E, Kraigher-Krainer E, Vasan RS (2011) Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail 13:18–28

    Article  PubMed  Google Scholar 

  • Lam CS, Rienstra M, Tay WT, Liu LC, Hummel YM, van der Meer P, de Boer RA, van Gelder I, Van Veldhuisen DJ, Voors AA, Hoendermis ES (2017) Atrial fibrillation in heart failure with preserved ejection fraction: association with exercise capacity, left ventricular filling pressures, natriuretic peptides, and left atrial volume. JACC Heart Fail 5:92–98

    Article  PubMed  Google Scholar 

  • Ling LH, Kistler PM, Ellims AH, Iles LM, Lee G, Hughes GL, Kalman JM, Kaye DM, Taylor AJ (2012) Diffuse ventricular fibrosis in atrial fibrillation: noninvasive evaluation and relationships with aging and systolic dysfunction. J Am Coll Cardiol 60:2402–2408

    Article  PubMed  Google Scholar 

  • Maesen B, Nijs J, Maessen J, Allessie M, Schotten U (2012) Post-operative atrial fibrillation: a maze of mechanisms. Europace 14:159–174

    Article  PubMed  Google Scholar 

  • Martin-Fernandez B, Gredilla R (2016) Mitochondria and oxidative stress in heart aging. Age (Dordr) 38:225–238

    Article  CAS  Google Scholar 

  • Martos R, Baugh J, Ledwidge M, O’Loughlin C, Conlon C, Patle A, Donnelly SC, McDonald K (2007) Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation 115:888–895

    Article  PubMed  Google Scholar 

  • Martos R, Baugh J, Ledwidge M, O’Loughlin C, Murphy NF, Conlon C, Patle A, Donnelly SC, McDonald K (2009) Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover. Eur J Heart Fail 11:191–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 14:803–869

    Article  CAS  PubMed  Google Scholar 

  • Meyer M, Schillinger W, Pieske B, Holubarsch C, Heilmann C, Posival H, Kuwajima G, Mikoshiba K, Just H, Hasenfuss G (1995) Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 92:778–784

    Article  CAS  PubMed  Google Scholar 

  • Najafi A, Sequeira V, Kuster DW, van der Velden J (2016) Beta-adrenergic receptor signalling and its functional consequences in the diseased heart. Eur J Clin Invest 46:362–374

    Article  CAS  PubMed  Google Scholar 

  • Nakou ES, Parthenakis FI, Kallergis EM, Marketou ME, Nakos KS, Vardas PE (2016) Healthy aging and myocardium: a complicated process with various effects in cardiac structure and physiology. Int J Cardiol 209:167–175

    Article  CAS  PubMed  Google Scholar 

  • Neuman RB, Bloom HL, Shukrullah I, Darrow LA, Kleinbaum D, Jones DP, Dudley SC Jr (2007) Oxidative stress markers are associated with persistent atrial fibrillation. Clin Chem 53:1652–1657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ng B, Connors LH, Davidoff R, Skinner M, Falk RH (2005) Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med 165:1425–1429

    Article  PubMed  Google Scholar 

  • Olivetti G, Melissari M, Capasso JM, Anversa P (1991) Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 68:1560–1568

    Article  CAS  PubMed  Google Scholar 

  • Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, Salvi F, Ciliberti P, Pastorelli F, Biagini E, Coccolo F, Cooke RM, Bacchi-Reggiani L, Sangiorgi D, Ferlini A, Cavo M, Zamagni E, Fonte ML, Palladini G, Salinaro F, Musca F, Obici L, Branzi A, Perlini S (2009) Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 120:1203–1212

    Article  CAS  PubMed  Google Scholar 

  • Ren J, Pulakat L, Whaley-Connell A, Sowers JR (2010) Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J Mol Med (Berl) 88:993–1001

    Article  CAS  Google Scholar 

  • Respress JL, van Oort RJ, Li N, Rolim N, Dixit SS, deAlmeida A, Voigt N, Lawrence WS, Skapura DG, Skardal K, Wisloff U, Wieland T, Ai X, Pogwizd SM, Dobrev D, Wehrens XH (2012) Role of RyR2 phosphorylation at S2814 during heart failure progression. Circ Res 110:1474–1483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rocken C, Peters B, Juenemann G, Saeger W, Klein HU, Huth C, Roessner A, Goette A (2002) Atrial amyloidosis: an arrhythmogenic substrate for persistent atrial fibrillation. Circulation 106:2091–2097

    Article  PubMed  Google Scholar 

  • Rockey DC, Bell PD, Hill JA (2015) Fibrosis—a common pathway to organ injury and failure. N Engl J Med 372:1138–1149

    Article  CAS  PubMed  Google Scholar 

  • Santhanakrishnan R, Wang N, Larson MG, Magnani JW, McManus DD, Lubitz SA, Ellinor PT, Cheng S, Vasan RS, Lee DS, Wang TJ, Levy D, Benjamin EJ, Ho JE (2016) Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction. Circulation 133:484–492

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma K, Kass DA (2014) Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circ Res 115:79–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song Y, Yao Q, Zhu J, Luo B, Liang S (1999) Age-related variation in the interstitial tissues of the cardiac conduction system; and autopsy study of 230 Han Chinese. Forensic Sci Int 104:133–142

    Article  CAS  PubMed  Google Scholar 

  • Steiner I (1987) The prevalence of isolated atrial amyloid. J Pathol 153:395–398

    Article  CAS  PubMed  Google Scholar 

  • Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8:143–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L (2008) Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med 40:232–239

    Article  CAS  PubMed  Google Scholar 

  • Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS (2015) Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta 1847:1424–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unger T, Li J (2004) The role of the renin-angiotensin-aldosterone system in heart failure. J Renin Angiotensin Aldosterone Syst 5(Suppl 1):S7–10

    Article  CAS  PubMed  Google Scholar 

  • Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM (1999) Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 85:428–436

    Article  PubMed  Google Scholar 

  • Verbrugge FH, Tang WH, Mullens W (2015) Renin-Angiotensin-aldosterone system activation during decongestion in acute heart failure: friend or foe? JACC Heart Fail 3:108–111

    Article  PubMed  Google Scholar 

  • Voigt N, Li N, Wang Q, Wang W, Trafford AW, bu-Taha I, Sun Q, Wieland T, Ravens U, Nattel S, Wehrens XH, Dobrev D (2012) Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na + −Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 125:2059–2070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie W, Santulli G, Reiken SR, Yuan Q, Osborne BW, Chen BX, Marks AR (2015) Mitochondrial oxidative stress promotes atrial fibrillation. Sci Rep 5:11427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu A, Narayanan N (1998) Effects of aging on sarcoplasmic reticulum Ca2 + −cycling proteins and their phosphorylation in rat myocardium. Am J Physiol 275:H2087–H2094

    CAS  PubMed  Google Scholar 

  • Yakes FM, Van HB (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci U S A 94:514–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S (2014) Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol 6:213–220

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Funding was provided by the ‘Institut National de la Santé et de la Recherche Médicale’ (INSERM).

Author information

Authors and Affiliations

  1. l’institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France

    Marja Steenman

  2. l’institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France

    Gilles Lande

Authors
  1. Marja Steenman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gilles Lande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marja Steenman.

Ethics declarations

Conflict of interests

Marja Steenman declares that she has no conflict of interest.

Gilles Lande declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Steenman, M., Lande, G. Cardiac aging and heart disease in humans. Biophys Rev 9, 131–137 (2017). https://doi.org/10.1007/s12551-017-0255-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12551-017-0255-9

Keywords

Search

Navigation