Emerging role of aging in the progression of NAFLD to HCC

With the aging of global population, the incidence of nonalcoholic fatty liver disease (NAFLD) has surged in recent decades. NAFLD is a multifactorial disease that follows a progressive course, ranging from simple fatty liver, nonalcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC). It is well established that aging induces pathological changes in liver and potentiates the occurrence and progression of NAFLD, HCC and other age-related liver diseases. Studies of senescent cells also indicate a pivotal engagement in the development of NAFLD via diverse mechanisms. Moreover, nicotinamide adenine dinucleotide (NAD⁺), silence information regulator protein family (sirtuins), and mechanistic target of rapamycin (mTOR) are three vital and broadly studied targets involved in aging process and NAFLD. Nevertheless, the crucial role of these aging-associated factors in aging-related NAFLD remains underestimated. Here, we reviewed the current research on the roles of aging, cellular senescence and three aging-related factors in the evolution of NAFLD to HCC, aiming at inspiring promising therapeutic targets for aging-related NAFLD and its progression.