How Aging Impacts Liver Scarring: New Insights into Hepatic Stellate Cells

The liver has an amazing ability to repair itself after injury. However, as we age, the liver becomes more prone to developing fibrosis or scarring after damage occurs. Fibrosis impairs normal liver function and can progress to serious conditions like cirrhosis and liver failure.A new study published in Scientific Reports sheds light on how the aging process promotes liver fibrosis. The research focused on hepatic stellate cells (HSCs), which play a central role in liver scarring. Normally HSCs remain in a quiescent state, but after liver injury they become activated and deposit collagen, the main component of scar tissue.

Key findings from the study include:

  • HSCs from aged mice (24 months old) showed increased activation and collagen production compared to HSCs from young mice (3 months old) when stimulated with pro-fibrotic factors.
  • Aged HSCs had higher expression of genes involved in cell senescence, a process where cells stop dividing and undergo changes that promote inflammation and fibrosis. Senescent HSCs secreted more inflammatory and fibrogenic molecules.
  • Eliminating senescent HSCs using senolytics, drugs that selectively remove senescent cells, reduced liver fibrosis in aged mice with liver injury. This suggests targeting senescent HSCs could be a promising anti-fibrotic therapy.
  • Mechanistically, the study found aging impaired the activity of sirtuins, a family of proteins that regulate cellular health and have been implicated in longevity. Restoring sirtuin activity in aged HSCs reduced their fibrogenic activity.
Photomicrographs of liver sections

In summary, this research reveals that aging-associated changes in HSCs, particularly cell senescence and sirtuin dysfunction, are key drivers of the increased susceptibility to liver fibrosis in old age. Developing ways to target senescent HSCs and boost sirtuin activity could lead to new treatments to combat liver fibrosis in the elderly. As our population ages, understanding and addressing the unique challenges of liver disease in older adults will become increasingly important.