Like a phoenix rising from the ashes, the human liver possesses a remarkable capacity to regenerate itself—making this vital organ practically ageless.
Exceptional Self-Healing Abilities
As our body’s largest internal organ, the liver possesses a remarkable capacity for self-repair. Even after up to 90 percent removal, it can regrow to full size and resume normal function. Furthermore, transplanted partial livers grow to completion within weeks.The liver is always less than 3 years old on average, regardless of a person’s age, according to a recent German study. Liver cell renewal is unaffected by aging, making the organ perpetually youthful. With proper health, even older people can have young livers.
These regenerative abilities are vital for the liver’s many crucial roles, including bile production, plasma protein and cholesterol synthesis, blood glucose regulation, hemoglobin processing, blood detoxification, clotting regulation, and bacteria removal from the bloodstream.
How Does the Liver Get Its Regeneration Capability?
The liver’s regenerative abilities stem from its unique cellular structure and internal division into lobes, Dr. Brian Kessler, who specializes in sports medicine, pain management, and rehabilitative medicine, told The Epoch Times.Liver Parts Can Regrow Independently
The liver contains four lobes—left, right, caudate, and quadrate—and each can regenerate independently.If one or more lobes are removed, they don’t regrow. As the remaining lobes undergo compensatory hyperplasia, proliferating and expanding in size until the liver regains its original mass, they take over the functions of the removed ones. The liver’s overall shape is permanently changed after regeneration, but its function is fully restored.
Liver Cells Divide to Repopulate Damaged Tissues
The liver’s lobules, the building blocks of the liver tissue, reveal another secret behind the organ’s renewable powers. Lobules comprise hexagonal arrangements of hepatocytes (liver cells) clustered around a central vein. Each lobule has three zones with distinct roles.
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Zones 1 and 3 hepatocytes produce metabolic enzymes responsible for survival and homeostasis, according to a 2021 study.
Researchers also identified a signaling pathway that activates zone 2 cells to repopulate injured tissue in the other zones. This zonal compartmentalization allows efficient targeted renewal of damaged regions, enabling the liver’s regenerative capacity. Though identical in type, zonation lets hepatocytes alter their function based on location.
Growth Factors Stimulate Cell Growth
The liver’s regeneration capacity also relies on specialized growth factors that are released when the organ is injured, according to Dr. Kessler.
The hepatocyte growth factor (HGF) and its specialized receptor (MET) are key players. HGF activates MET to induce cell proliferation, migration, and the formation of new blood vessels in organs, including the liver. This pathway facilitates the development, regeneration, and reduction of tissue scarring.
Other Supporting Systems
The liver relies on several other supporting systems to regenerate itself.For instance, the liver’s extensive blood vessel network heavily influences its ability to regenerate, which relies on the creation of new blood vessels. Platelets accumulating in the liver post-injury contain growth factors. The blood-clotting protein fibrinogen signals platelets to accumulate, and its levels may predict regeneration success.
The immune cells in the liver, including natural killer T cells, natural killer cells, and regulatory T cells, reduce inflammation (pdf) to aid tissue healing.
Additionally, the extracellular matrix (ECM), a dynamic scaffolding around liver cells, undergoes constant remodeling, especially during injury repair. The ECM structurally supports liver cells and is composed of water, proteins, and proteoglycans.
How Does the Liver Regenerate Itself?
Liver regeneration occurs in two scenarios.Partial Liver Resection
Partial hepatectomy removes part of the liver to treat tumors or cancer or to obtain a partial liver for transplant. The goal is to regenerate the total hepatocyte count and mass through cell proliferation and enlargement.In a living-donor transplant, the recipient’s diseased liver is replaced with part of the donor’s healthy liver.
After the surgery, both donor and recipient livers regenerate to full size within weeks.
Liver Cell Activation for Tissue Repair
Liver injuries from toxins, viruses, or immune attacks trigger inflammation and activate immune cells to release cytokines and growth factors, initiating regeneration. Near the injury, hepatocytes rapidly divide to replace lost cells.The liver also produces small epithelial cells that can differentiate to regenerate damaged tissue.
In severe cases, if hepatocytes are insufficient, hepatic progenitor cells activate and differentiate to repair the liver.
The Liver Knows Just When to Grow and Shrink
The liver can precisely control its growth and size, even shrinking when needed.For example, a British study found that mouse livers decreased in weight during alternate-day fasting for one week, affecting metabolism. But upon resuming normal eating, proliferation increased and the livers regained their original size.
Similarly, low-sugar diets deplete glycogen, causing temporary liver shrinkage.
When Is Damage Irreversible?
Certain diseases and toxins can overwhelm repair mechanisms and cause permanent damage despite the liver’s regenerative capacity.Even though the liver metabolizes medications and toxins, some drugs taken excessively or with alcohol can harm the liver beyond its ability to heal. These include NSAIDs, or nonsteroidal anti-inflammatory drugs, such as ibuprofen, amiodarone (for heart rhythm problems), birth control pills, statins, anti-seizure medications, and high-dose niacin (vitamin B3).
Repeated severe injury causes accumulating scar tissue, called fibrosis, which can advance to cirrhosis—permanent damage impairing liver function.
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Maintaining liver health through moderation and awareness is vital in preserving the organ’s lifelong regenerative potential.
How to Help the Liver Regenerate
“To speed up your liver regeneration, whatever the cause of the damage, you need to stop damaging it first,” Dr. Kessler said. Adopting a healthy lifestyle in the following ways helps:- Avoid alcohol: “Limiting alcohol consumption is crucial, as excessive alcohol intake can lead to liver damage and impair the regenerative capacity of the liver,” Dr. Saurabh Sethi, a Harvard- and Stanford-trained hepatologist, told The Epoch Times.
- Avoid smoking: Smoking increases the risk of fatty liver disease, the most common chronic liver condition.
- Avoid illegal substances: Using substances such as amphetamines, cocaine, and khat (an herbal stimulant) can cause liver disorders ranging from mild dysfunction to sudden failure.
- Manage weight: Excess weight increases the risk of fatty liver disease, affecting up to 90 percent of those with severe obesity.
- Eat healthy: Adopting a healthy lifestyle is essential for maintaining a youthful liver, Dr. Sethi said. “This includes consuming a balanced diet that is rich in fruits, vegetables, and whole grains.” Garlic also has compounds that improve liver health.
Therapies
Emerging therapies to enhance liver regeneration include the following:- Liver tissue engineering: This regenerative medicine approach aims to repair, regenerate, or replace damaged tissue to re-create liver function and treat acute or chronic liver diseases.
- Small molecule drugs: These assist transplanted hepatocyte repopulation by promoting proliferation, overcoming their limited engraftment. This is a potential treatment option for end-stage liver disease.
- Yamanaka factors: These help make liver cells younger, accelerating healing. These embryonic stem cell factors can make liver cells younger by in vivo cellular reprogramming.
- Stem cell extracellular vesicles: Stem cells release biological nanoparticles known as extracellular vesicles, which reduce damage and boost repair.
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