Anderson R

Arthur H

Dodds R

Owens WA

Passos JF

Redgrave R

Richardson GD

Saretzki G

TualChalot S

vonZglinicki T

Aim: Ageing is associated with both increased prevalence of cardiovascular disease and a poorer prognosis following myocardial infarction (MI). The link between the impact of ageing as a contributing factor in cardiovascular disease and the cellular biology of cardiac ageing is not completely understood. In rapidly dividing tissues ageing is associated with attenuated regeneration. We have also demonstrated that the same may be true of the heart. The aim of this study was to determine the mechanism underling attenuated regeneration and to ascertain if impaired regeneration contributes to poorer outcome following myocardial infarction aged individuals. Methods: Cardiomyocyte (CM) turnover and senescence was quantified in young and aged Mouse and Human hearts. Transgenic models of oxidative stress were used to investigate the mechanisms driving cardiac ageing. The LAD-ligation model of MI was used to test if attenuated regenerative potential is characteristic of cardiovascular ageing. Results: Within the CM population there is an age dependent increased oxidative stress and the accumulation of senescence. CM specific increased oxidative stress results in CM senescence and heart failure. Furthermore, we have shown that treatment with antioxidants reduced senescence and improved heart function in these mice. Conclusion: We hypothesize that increased oxidative stress in the ageing heart results in an accumulation of CM senescence, which impairs CM turnover, predisposing the aged heart to myocardial dysfunction and disease. We are now testing if these processes contribute to poorer outcome and increased progression to heart failure if insult does occur, such as MI, in the aged heart

Newcastle University E-Prints

The role of cardiomyocyte senescence and regeneration in Ageing

The role of cardiomyocyte senescence and regeneration in Ageing

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