Research on the use of senolytic drugs to treat liver disease has shown an unexpected increase in disease severity.

Manlio Vinciguerra, Ph.D., MSc, the head of the Epigenetics, Metabolism and Aging research team at International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), collaborated with colleagues from other institutions to publish a study on the use of senolytic drugs dasatinib and quercetin (D+Q) in targeting obesity and age-dependent nonalcoholic fatty liver disease (NAFLD) in mice xenografted with human hepatocellular carcinoma (HCC) cells.

NAFLD affects more than 25% of the population and is the most common chronic liver disease. It poses a challenge in both prevention and treatment and can lead to the development of fibrosis, cirrhosis, and even HCC, which is the main cause of cancer-related deaths.

The study used senolytic drugs, which target and eliminate senescent cells. Senescent cells are those that have permanently stopped dividing but did not die. While senescence is essential for many functions such as homeostasis or limiting tumor growth, many studies have already shown that when senescent cells accumulate, they can become harmful to other healthy tissues. “In the context of liver disease progression, the concept of selective elimination of senescent cells using senolytics holds a great therapeutic potential,” states Vinciguerra, as the use of senolytics presents a promising way to treat not only NAFLD but also many other age-related diseases.

The results have shown that the specific combination of (D+Q) used to treat NAFLD in mice has unexpectedly led to a mild increase in the severity of the disease, and the study thus concluded that the combination of senolytics used was ineffective in the treatment of NAFLD-caused HCC. “While elimination of some senescent cells is beneficial for healthy aging and overall lifespan, it is very important to identify which senescent cells are targeted by specific senolytics and their overall effects on health span,” explained Vinciguerra.

You can find the study here: