Researchers have discovered a natural compound in citrus fruits that may help slow down some signs of liver aging.
The liver is known for its exceptional ability to regenerate its cells and performs hundreds of vital functions, including processing nutrients and filtering harmful substances from the blood. With age, however, liver efficiency gradually declines, and the liver becomes more susceptible to fat accumulation, inflammation, and other age-related problems.
The researchers found that hesperetin, a natural flavonoid compound found in citrus fruits such as oranges and lemons, may help maintain liver function in elderly mice by activating a gene associated with longevity known as CISD2.
This gene plays a crucial role in maintaining liver health and regulating metabolism, but its activity declines with age. The study suggests that restoring its activity may be one potential way to mitigate changes associated with liver aging.
To test this, a team led by molecular biologist Chao-Ching Chen of National Yang-Ming Chiao Tong University in Taiwan gave elderly mice, aged 21 months, a daily dose of hesperetin for five months, while another group received an inactive substance for comparison.
After the experiment concluded, the researchers found that Cisd2 levels in the livers of mice that received hesperetin remained close to those found in young mice, even as the mice aged. In contrast, gene levels decreased significantly in mice that did not receive the compound.
The effect was not limited to gene activity, as the treated mice showed a decrease in a number of markers associated with age-related liver deterioration, including fat accumulation, liver cell damage, and inflammation.
Gene activity analysis also showed that hisperetin pushed the liver cells of the treated mice toward a pattern more similar to that found in young animals, and reversed some of the genetic changes that appeared with age.
The researchers then tested whether the Cisd2 protein was necessary for hisperetin to function. For this purpose, they used genetically modified mice lacking the protein in their main liver cells. These mice showed early signs of liver deterioration and did not benefit from hisperetin treatment.
This result indicates that the effect of hesperetin is highly dependent on the presence of Cisd2, and that the compound most likely works through a signaling pathway involving two other proteins, Hmgcs2 and Pparα, and that this pathway helps to increase Cisd2 activity.
To determine if the same pathway exists in humans, researchers analyzed samples of healthy liver tissue from 80 patients who had undergone surgery for liver cancer or benign tumors. They found that PPARα and CISD2 levels were lower in older individuals, consistent with findings observed in mice.
However, the researchers emphasize that these results do not yet prove that hesperetin can slow liver aging in humans. The primary study was conducted on mice, and further research is needed to determine the compound's effectiveness and safety in humans.
The results may open the door to future studies exploring the potential use of hesperetin, extracted from citrus fruits and other sources, to help maintain liver health with age or reduce some age-related diseases.
The study was published in the journal npj Aging.
