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The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro- pathways is essential to discover new approaches to regenerative therapies.The myocardium is characterized by limited regenerative capacity.FSTL1 is an epicardial cardiogenic factor with dynamic expression after injury.The rejuvenating effects can be mediated by blood-borne ‘pro-youthful’ factors.Several growth hormone responses affect multiple signalling cascades.