Liver is a pivotal metabolic organ that is responsible for xenobiotic detoxification, protein synthesis, bile production and energetic balance. Aging of the liver manifests as multiple functional and structural alterations . Cisd2, the second member of the CDGSH iron-sulfur domain-containing protein family in mammals, has been shown to serve as an anti-aging protein that can modulate longevity and maintain cellular homeostasis . Here our laboratory highlights a key factor underlying liver dysfunction during aging, which is a reduction in Cisd2 expression . In a series of mouse studies, the robust protective effects of Cisd2 on age-associated or diet-induced liver damage were demonstrated. In agreement with the above, a persistently high level of Cisd2 appears to slow down the aging rate of liver in mice and the results are likely to be similar in humans (summarized in Figure 1A).