Journal article 136 views 4 downloads
Senescence-related myocardial dysfunction: keeping a young heart
Ramzi A Ajjan 
,
Robert T R Huckstepp ,
Naveed Akbar ,
Johann Bauersachs ,
Jesher Ching Wai Lok,
Juel Choppy-Madeleine,
Gary Christopher ,
Mayank Dalakoti ,
Emily Dawson-Plincke,
John Dodds,
Georgina M Ellison-Hughes ,
Costanza Emanueli ,
Christopher George ,
Anushka Goyal,
Victoria Higginbotham,
Lorenz Holzner,
Venkat Kanamarlapudi ,
Paolo Madeddu ,
Claudio Mauro ,
Fiona Lewis-McDougall ,
Andrew J Murray ,
Renita Peter Damien Genetus,
Emma Short ,
Mark A Sussman ,
Adriana A S Tavares ,
Samuel Thompson,
Morya Wadodkar,
Stuart R G Calimport ,
Barry L Bentley ,
Victoria Higginbotham
,
Robert T R Huckstepp ,
Naveed Akbar ,
Johann Bauersachs ,
Jesher Ching Wai Lok,
Juel Choppy-Madeleine,
Gary Christopher ,
Mayank Dalakoti ,
Emily Dawson-Plincke,
John Dodds,
Georgina M Ellison-Hughes ,
Costanza Emanueli ,
Christopher George ,
Anushka Goyal,
Victoria Higginbotham,
Lorenz Holzner,
Venkat Kanamarlapudi ,
Paolo Madeddu ,
Claudio Mauro ,
Fiona Lewis-McDougall ,
Andrew J Murray ,
Renita Peter Damien Genetus,
Emma Short ,
Mark A Sussman ,
Adriana A S Tavares ,
Samuel Thompson,
Morya Wadodkar,
Stuart R G Calimport ,
Barry L Bentley ,
Victoria Higginbotham
European Heart Journal
Swansea University Authors:
Gary Christopher , Christopher George , Venkat Kanamarlapudi , Victoria Higginbotham
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© The Author(s) 2026. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
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DOI (Published version): 10.1093/eurheartj/ehag095
Abstract
The heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the...
| Published in: | European Heart Journal |
|---|---|
| ISSN: | 0195-668X 1522-9645 |
| Published: |
Oxford University Press (OUP)
2026
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71384 |
| first_indexed |
2026-02-03T14:59:42Z |
|---|---|
| last_indexed |
2026-03-13T05:24:49Z |
| id |
cronfa71384 |
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| fullrecord |
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It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium’s regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing.</abstract><type>Journal Article</type><journal>European Heart Journal</journal><volume>0</volume><journalNumber/><paginationStart/><paginationEnd/><publisher>Oxford University Press (OUP)</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0195-668X</issnPrint><issnElectronic>1522-9645</issnElectronic><keywords/><publishedDay>6</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2026</publishedYear><publishedDate>2026-03-06</publishedDate><doi>10.1093/eurheartj/ehag095</doi><url/><notes/><college>COLLEGE NANME</college><department>Health and Social Care School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>HSOC</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>British Heart Foundation, Health and Care Research Wales, UKRI, Wellcome Trust, BBSRC, Diabetes UK, NIHR, Abbott, EU, Tobacco Related Disease Research Program (US)</funders><projectreference/><lastEdited>2026-03-12T13:56:17.6780020</lastEdited><Created>2026-02-03T14:48:01.7138665</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Ramzi A</firstname><surname>Ajjan</surname><orcid>0000-0002-1636-3725</orcid><order>1</order></author><author><firstname>Robert T R</firstname><surname>Huckstepp</surname><orcid>0000-0003-4410-3397</orcid><order>2</order></author><author><firstname>Naveed</firstname><surname>Akbar</surname><orcid>0000-0003-4620-6373</orcid><order>3</order></author><author><firstname>Johann</firstname><surname>Bauersachs</surname><orcid>0000-0002-9341-117x</orcid><order>4</order></author><author><firstname>Jesher Ching Wai</firstname><surname>Lok</surname><order>5</order></author><author><firstname>Juel</firstname><surname>Choppy-Madeleine</surname><order>6</order></author><author><firstname>Gary</firstname><surname>Christopher</surname><orcid>0000-0002-7175-6644</orcid><order>7</order></author><author><firstname>Mayank</firstname><surname>Dalakoti</surname><orcid>0000-0002-7091-7880</orcid><order>8</order></author><author><firstname>Emily</firstname><surname>Dawson-Plincke</surname><order>9</order></author><author><firstname>John</firstname><surname>Dodds</surname><order>10</order></author><author><firstname>Georgina M</firstname><surname>Ellison-Hughes</surname><orcid>0000-0002-2733-3361</orcid><order>11</order></author><author><firstname>Costanza</firstname><surname>Emanueli</surname><orcid>0000-0002-2392-0702</orcid><order>12</order></author><author><firstname>Christopher</firstname><surname>George</surname><orcid>0000-0001-9852-1135</orcid><order>13</order></author><author><firstname>Anushka</firstname><surname>Goyal</surname><order>14</order></author><author><firstname>Victoria</firstname><surname>Higginbotham</surname><order>15</order></author><author><firstname>Lorenz</firstname><surname>Holzner</surname><order>16</order></author><author><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><orcid>0000-0002-8739-1483</orcid><order>17</order></author><author><firstname>Paolo</firstname><surname>Madeddu</surname><orcid>0000-0002-4718-9205</orcid><order>18</order></author><author><firstname>Claudio</firstname><surname>Mauro</surname><orcid>0000-0002-3736-0099</orcid><order>19</order></author><author><firstname>Fiona</firstname><surname>Lewis-McDougall</surname><orcid>0000-0001-7273-639x</orcid><order>20</order></author><author><firstname>Andrew J</firstname><surname>Murray</surname><orcid>0000-0002-0929-9315</orcid><order>21</order></author><author><firstname>Renita Peter Damien</firstname><surname>Genetus</surname><order>22</order></author><author><firstname>Emma</firstname><surname>Short</surname><orcid>0000-0001-5050-589x</orcid><order>23</order></author><author><firstname>Mark A</firstname><surname>Sussman</surname><orcid>0000-0002-0104-4799</orcid><order>24</order></author><author><firstname>Adriana A S</firstname><surname>Tavares</surname><orcid>0000-0001-7505-9144</orcid><order>25</order></author><author><firstname>Samuel</firstname><surname>Thompson</surname><order>26</order></author><author><firstname>Morya</firstname><surname>Wadodkar</surname><order>27</order></author><author><firstname>Stuart R G</firstname><surname>Calimport</surname><orcid>0000-0002-0085-0385</orcid><order>28</order></author><author><firstname>Barry L</firstname><surname>Bentley</surname><orcid>0000-0002-4360-5902</orcid><order>29</order></author><author><firstname>Victoria</firstname><surname>Higginbotham</surname><orcid/><order>30</order></author></authors><documents><document><filename>71384__36368__5cb51762309f4d0c9cd049c9b8fdd0e6.pdf</filename><originalFilename>ehag095.pdf</originalFilename><uploaded>2026-03-09T09:54:45.0356253</uploaded><type>Output</type><contentLength>1998922</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© The Author(s) 2026. 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2026-03-12T13:56:17.6780020 v2 71384 2026-02-03 Senescence-related myocardial dysfunction: keeping a young heart 8092562c67809dfda89f7bb8582874d3 0000-0002-7175-6644 Gary Christopher Gary Christopher true false a2e211f7bd379c81e9c393637803a0a0 0000-0001-9852-1135 Christopher George Christopher George true false 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 29dd07a8a73cf872888e406e01ee766f Victoria Higginbotham Victoria Higginbotham true false 2026-02-03 HSOC The heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium’s regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing. Journal Article European Heart Journal 0 Oxford University Press (OUP) 0195-668X 1522-9645 6 3 2026 2026-03-06 10.1093/eurheartj/ehag095 COLLEGE NANME Health and Social Care School COLLEGE CODE HSOC Swansea University Another institution paid the OA fee British Heart Foundation, Health and Care Research Wales, UKRI, Wellcome Trust, BBSRC, Diabetes UK, NIHR, Abbott, EU, Tobacco Related Disease Research Program (US) 2026-03-12T13:56:17.6780020 2026-02-03T14:48:01.7138665 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Ramzi A Ajjan 0000-0002-1636-3725 1 Robert T R Huckstepp 0000-0003-4410-3397 2 Naveed Akbar 0000-0003-4620-6373 3 Johann Bauersachs 0000-0002-9341-117x 4 Jesher Ching Wai Lok 5 Juel Choppy-Madeleine 6 Gary Christopher 0000-0002-7175-6644 7 Mayank Dalakoti 0000-0002-7091-7880 8 Emily Dawson-Plincke 9 John Dodds 10 Georgina M Ellison-Hughes 0000-0002-2733-3361 11 Costanza Emanueli 0000-0002-2392-0702 12 Christopher George 0000-0001-9852-1135 13 Anushka Goyal 14 Victoria Higginbotham 15 Lorenz Holzner 16 Venkat Kanamarlapudi 0000-0002-8739-1483 17 Paolo Madeddu 0000-0002-4718-9205 18 Claudio Mauro 0000-0002-3736-0099 19 Fiona Lewis-McDougall 0000-0001-7273-639x 20 Andrew J Murray 0000-0002-0929-9315 21 Renita Peter Damien Genetus 22 Emma Short 0000-0001-5050-589x 23 Mark A Sussman 0000-0002-0104-4799 24 Adriana A S Tavares 0000-0001-7505-9144 25 Samuel Thompson 26 Morya Wadodkar 27 Stuart R G Calimport 0000-0002-0085-0385 28 Barry L Bentley 0000-0002-4360-5902 29 Victoria Higginbotham 30 71384__36368__5cb51762309f4d0c9cd049c9b8fdd0e6.pdf ehag095.pdf 2026-03-09T09:54:45.0356253 Output 1998922 application/pdf Version of Record true © The Author(s) 2026. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. true eng https://creativecommons.org/licenses/by/4.0/ |
| title |
Senescence-related myocardial dysfunction: keeping a young heart |
| spellingShingle |
Senescence-related myocardial dysfunction: keeping a young heart Gary Christopher Christopher George Venkat Kanamarlapudi Victoria Higginbotham |
| title_short |
Senescence-related myocardial dysfunction: keeping a young heart |
| title_full |
Senescence-related myocardial dysfunction: keeping a young heart |
| title_fullStr |
Senescence-related myocardial dysfunction: keeping a young heart |
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Senescence-related myocardial dysfunction: keeping a young heart |
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Senescence-related myocardial dysfunction: keeping a young heart |
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8092562c67809dfda89f7bb8582874d3 a2e211f7bd379c81e9c393637803a0a0 63741801137148abfa4c00cd547dcdfa 29dd07a8a73cf872888e406e01ee766f |
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8092562c67809dfda89f7bb8582874d3_***_Gary Christopher a2e211f7bd379c81e9c393637803a0a0_***_Christopher George 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi 29dd07a8a73cf872888e406e01ee766f_***_Victoria Higginbotham |
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Gary Christopher Christopher George Venkat Kanamarlapudi Victoria Higginbotham |
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Ramzi A Ajjan Robert T R Huckstepp Naveed Akbar Johann Bauersachs Jesher Ching Wai Lok Juel Choppy-Madeleine Gary Christopher Mayank Dalakoti Emily Dawson-Plincke John Dodds Georgina M Ellison-Hughes Costanza Emanueli Christopher George Anushka Goyal Victoria Higginbotham Lorenz Holzner Venkat Kanamarlapudi Paolo Madeddu Claudio Mauro Fiona Lewis-McDougall Andrew J Murray Renita Peter Damien Genetus Emma Short Mark A Sussman Adriana A S Tavares Samuel Thompson Morya Wadodkar Stuart R G Calimport Barry L Bentley Victoria Higginbotham |
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European Heart Journal |
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The heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium’s regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing. |
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2026-03-06T05:34:37Z |
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11.099609 |