In HF, although early studies found that circulating IGF1 was inversely associated with HF risk in older adults[35], more recent work has elegantly shown that when IGF1R signaling is directly modulated in the heart, it displays a more similar pattern to aging, in which IGF1R activation improves cardiac function in young animals, but promotes heart failure in older ones[36,37]. This evidence concerns the gene IGF1 and hydrops fetalis.