Owing to genome instability and dysregulated metabolism, Sirt6-deficient mice exhibit aging-associated degenerative phenotypes, including severe metabolic disorders, subcutaneous fat loss, and lordokyphosis, finally dying at about 4 weeks old; in contrast, transgenic mice overexpressing Sirt6 show a longer lifespan than their wild-type counterparts [63, 64]. Here, SIRT6 is linked to metabolic disease.