Thymosin beta-4 denotes new directions towards developing prosperous anti-aging regenerative therapies

•Thymosin beta-4 (TB4) is expressed in the mammalian heart during embryonic development and in adults.•TB4 increases mammalian myocardial cell migration, endothelial cell proliferation and initiates capillary formation in vitro.•Systemic injection of TB4 increases post-ischemic cardiac function in adult mammals.•Systemic administration of TB4 inhibits myocardial cell death, initiates coronary re-growth and activates endogenous vessel and myocardial progenitor cells of the adult heart in vivo.•TB4 is capable of reminding the adult mammalian heart on its embryonic program and this regenerative capacity is independent of injury. Our dream of defeating the processes of organ damage and aging remains a challenge scientists pursued for hundreds of years. Although the goal is to successfully treat the body as a whole, steps towards regenerating individual organs are even considered significant. Since initial approaches utilizing only progenitor cells appear limited, we propose interconnecting our collective knowledge regarding aging and embryonic development may lead to the discovery of molecules which provide alternatives to effectively reverse cellular damage. In this review, we introduce and summarize our results regarding Thymosin beta-4 (TB4) to support our hypothesis using the heart as model system. Accordingly, we investigated the developmental expression of TB4 in mouse embryos and determined the impact of the molecule in adult animals by systemically injecting the peptide following acute cardiac infarction or with no injury. Our results proved, TB4 is expressed in the developing heart and promotes cardiac cell migration and survival. In adults, the peptide enhances myocyte survival and improves cardiac function after coronary artery ligation. Moreover, intravenous injections of TB4 alter the morphology of the adult epicardium, and the changes resemble the characteristics of the embryo. Reactivation of the embryonic program became equally reflected by the increased number of cardiac vessels and by the alteration of the gene expression profile typical of the embryonic state. Moreover, we discovered TB4 is capable of epicardial progenitor activation, and revealed the effect is independent of hypoxic injury. By observing the above results, we believe, further discoveries and consequential postnatal administration of developmentally relevant candidate molecules such as TB4 may likely result in reversing aging processes and accelerate organ regeneration in the