The heart: mostly postmitotic or mostly premitotic? Myocyte cell cycle, senescence, and quiescence

The concept of myocyte division and myocyte-mediated regeneration has re-emerged in the past 5 years through development of sophisticated transgenic mice and carbon-dating of cells. Although recently, a couple of studies have been conducted as an attempt to intervene in myocyte division, the efficiency in adult animals remains discouragingly low. Re-enforcing myocyte division is a vision that has been desired for decades, leading to years of experience in myocyte resistance to proproliferative stimuli. Previous attempts have indeed provided a platform for basic knowledge on molecular players and signalling in myocytes. However, natural biological processes such as hypertrophy and binucleation provide layers of complexity in interpretation of previous and current findings. A major hurdle in mediating myocyte division is a lack of insight in the myocyte cell cycle. To date, no knowledge is gained on myoycte cell cycle progression and/or duration. This review will include an overview of previous and current literature on myocyte cell cycle and division. Furthermore, the limitations of current approaches and basic questions that might be essential in understanding myocardial resistance to division will be discussed.