SIRT4 and cardiac hypertrophy: Interestingly, Sirt2, which protects against pathological cardiac hypertrophy [20] was increased with age in LV and SAN, whereas Sirt4, which is linked to pathologic cardiac hypertrophy [21] was downregulated with age in LV and SAN (Figure 4D and 4F), suggesting that LV and SAN upregulated Sirt2 but downregulated Sirt4 to fight against cardiac stress during aging.