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. This evidence concerns the gene SIRT2 and cardiac hypertrophy.