Citrus fruits can help the liver fight aging

The liver is one of the key organs, as it is responsible for metabolism, detoxification of toxins, and control of the immune response. With age, its cells undergo serious structural and functional changes, mitochondria are affected, oxidative stress increases, and the functioning of cellular systems is disrupted. This increases the risk of diseases such as metabolic liver dysfunction, steatohepatitis, and, in the long term, liver cancer. At the same time, the molecular mechanisms of liver aging are not fully understood, and there are still very few effective ways to slow down this process.

In a new study, scientists focused on the role of the Cisd2 gene, one of the key longevity genes, which protects mitochondria and maintains balance in the cell. It was previously known that in mice, maintaining a high level of Cisd2 prolongs life and slows down age‑related changes, while the loss of this gene, on the contrary, accelerates aging. Experts also took into account the role of Pparα, a protein that protects the liver, and Hmgcs2, which is involved in metabolic processes.

The experiment was conducted on 21‑month‑old mice (which corresponds to old age); the animals were divided into two groups. One received a regular diet with the addition of hesperetin (100 mg per kilogram of body weight per day) for five months, the other received a control diet without the supplement. In addition, some of the mice were deliberately deprived of the Cisd2 gene in liver cells to test how important its presence is for the effect of hesperetin.

An analysis of the activity of more than 10,000 genes showed that with age, the levels of Pparα and Cisd2 decrease, which makes the liver vulnerable to damage, fat accumulation, and inflammation. Hesperetin triggered a whole chain of molecular events: it interacted with Hmgcs2, stabilizing this protein, which allowed it to form a complex with Pparα. In turn, this duo enabled the production of the protective protein Cisd2. As a result, in mice that received hesperetin, the functioning of mitochondria and the systems responsible for proper protein folding was restored; signs of fatty liver degeneration, inflammation, and scar tissue formation were reduced; and liver damage indicators in the blood approached normal levels.

The experiment with mice lacking Cisd2 was particularly illustrative, as the effect of hesperetin was noticeably weaker in them. This confirmed that Cisd2 plays a central role in the recovery mechanism.

An important step towards understanding the universality of the mechanism was taken when it was possible to study liver samples from 80 patients who had undergone surgery. The analysis showed that the levels of Pparα and Cisd2 decrease consistently with age, regardless of gender, and higher Pparα values correlate with higher Cisd2 values. This suggests that the described pathway may also be significant for humans.

At the same time, the researchers do not claim that consuming citrus fruits can slow down liver aging. However, the discovered mechanism opens up prospects for the development of medications or thoroughly tested nutraceuticals aimed at preventing and treating age‑related liver diseases in older people.