The liver, as a key organ for detoxification and metabolism, plays a crucial role in overall health. However, its aging process can release senescence-associated secretory factors (such as TGFβ), triggering multi-organ dysfunction and accelerating systemic aging. This mechanism has been validated in both animal experiments and clinical studies, highlighting the importance of liver protection in delaying systemic aging.
The liver plays a crucial role in detoxification and is responsible for various tasks, including metabolism, detoxification, and energy storage. Recently, a paper published in Nature Cell Biology, a sub-journal of Nature, uncovered a new mechanism where liver damage promotes multi-organ aging. The study revealed that liver aging not only affects its own function but may also act as a "driver" of systemic aging.
This discovery serves as a wake-up call: protecting the liver is not just about the liver itself; it’s also about delaying aging and maintaining overall health. So, what are the consequences of liver aging, and how can we protect the liver scientifically?
The Harm of Liver Aging Is Greater Than You Think
The core of liver aging lies in the aging of liver cells. These cells enter a state known as "cellular senescence," characterized by halted cell division, decreased metabolic function, and a phenomenon called the senescence-associated secretory phenotype (SASP).
Initially, the substances secreted during SASP can play a local repair and protective role, such as limiting the extent of damage or promoting wound healing. However, as the number of aging cells increases, the secretion of SASP expands, and its negative effects begin to manifest.
Studies have shown that this aging state can spread, potentially leading to multi-organ dysfunction. In other words, severe liver aging not only reduces the efficiency of this "metabolic factory" but may also affect other systems in the body, creating a vicious cycle of systemic decline.
How Liver Aging Spreads Throughout the Body
The "spreading" problem of liver aging is complex, involving the transmission of cellular secretions, activation of signaling pathways, and response mechanisms in other organs.
Research indicates that senescent liver cells secrete large amounts of SASP factors, with transforming growth factor-beta (TGFβ) being identified as a key mediator. These factors travel through the bloodstream to distant organs, affecting systems such as the kidneys, brain, and lungs.
In a mouse model with liver-cell-specific aging, researchers observed a chain reaction of multi-organ aging. They found a significant increase in p21-expressing cells (a marker of cell cycle inhibition) in the kidneys, along with elevated plasma cystatin C levels, indicating decreased kidney filtration efficiency.
Mdm2Hep (liver senescence) mice have impaired renal function as evidenced by elevated cystatin C levels and increased urinary amino acid excretion
Moreover, the brain and lungs were similarly affected. In experiments, the hippocampal region of the mice showed significant p21 expression and cognitive decline.
For instance, in a Y-maze test, mice with liver-cell-induced aging spent significantly less time exploring new arms (dropping from 50% to about 20%) compared to the control group. This cognitive decline was closely linked to neuronal dysfunction in the hippocampus.In lung tissue, signs of fibrosis gradually emerged, suggesting that lung aging may be a long-term effect of liver aging.
Increased p21 expression in the brain and lungs of Mdm2Hep mice
The study revealed that blood TGFβ levels were significantly elevated in mice with liver aging. When the TGFβ signaling pathway was blocked, p21 expression in the kidneys and brain of these mice was markedly reduced, indicating a significant alleviation of organ aging. This finding confirms that TGFβ plays an indispensable role in the systemic spread of liver aging.
b-i: The results showed that the number of p21-positive cells in the kidneys, brain, and lungs of mice treated with TGFβR1 inhibitors was significantly reduced, and renal function was significantly improved.
Further validation in a cohort of patients with acute hepatitis showed that p21 and DNA damage marker γH2AX were significantly elevated in liver biopsy samples. These markers not only differentiated between survival and non-survival outcomes but were also significantly associated with multi-organ dysfunction.
For example, kidney function indicators (such as serum creatinine levels) in non-surviving patients deteriorated continuously during hospitalization. High p21 expression in liver tissues was positively correlated with the severity of kidney function decline.
b-c: The proportion of p21 and γH2AX positive cells in the non-survivor group was significantly higher than that in the survivor group, indicating that the degree of hepatocyte senescence is associated with disease prognosis.
d-e: The serum creatinine level in the non-survivor group increased significantly over time, indicating worsening renal function. The hepatocyte p21 level is associated with renal dysfunction.
f: Patients with higher p21 levels are more likely to develop hepatic encephalopathy, indicating that hepatocyte senescence is associated with central nervous system dysfunction.
Additionally, the high expression of these markers was linked to hepatic encephalopathy (such as cognitive impairment), suggesting that liver aging may affect brain function through systemic mechanisms.
These experiments demonstrated how liver aging transcends being a "local problem" to become a "core driver" of systemic health issues.
This reminds us that protecting the liver is not merely about maintaining the function of a single organ—it is about preventing the entire body from falling into an "aging chain." Especially during holidays, when high metabolic stress can exacerbate this spreading process, we need to pay extra attention to diet and lifestyle habits to avoid unnecessary health risks.
How to Protect the Liver
To protect the liver, managing diet and lifestyle scientifically is particularly important. Some simple adjustments can effectively reduce the liver's burden and slow down its aging process.
1. Dietary Habits
Maintain a balanced diet, avoiding foods high in sugar, fat, and salt. Refrain from consuming excessive greasy foods and desserts to reduce the liver's metabolic stress. It's best to avoid smoking and drinking alcohol.
2. Lifestyle Habits
Maintain a regular schedule, as this is key to liver protection. Chronic sleep deprivation disrupts the liver's biological rhythm and reduces its repair capacity. Moderate exercise helps enhance metabolism, but intense exercise should be avoided to prevent oxidative stress. Additionally, managing emotions and reducing stress can significantly improve the liver's overall condition.
3. Regular Check-ups
If possible, regular health check-ups are a good choice, especially focusing on liver function indicators and potential conditions like fatty liver or inflammation. For those who drink alcohol, setting one or two "alcohol-free days" per week can give the liver more time to repair itself.
A healthy liver is the foundation of a high-quality life. As we enjoy the upcoming Spring Festival reunion, using scientific dietary and lifestyle choices to lighten the liver's load will make these festive times worry-free and joyful.