Your Liver May Hold the Key to Healthy Aging

A Conversation About: Aging and Metabolic Disorders - YouTube

 Scientists discover how metabolic health and longevity are intimately linked—and what you can do about it

La Jolla, California — Imagine two identical twins in their 40s. One maintains a healthy weight and exercises regularly. The other carries extra pounds around the middle and lives a sedentary life. Fast-forward 20 years, and their aging trajectories will likely look dramatically different—not just in appearance, but in how their bodies function at the cellular level.

The difference, scientists now understand, lies largely in the liver.

In what amounts to a revolution in our understanding of aging, researchers have discovered that fatty liver disease—a condition affecting nearly one in three American adults—doesn't just damage your liver. It accelerates aging throughout your entire body, increasing your risk of heart disease, diabetes, dementia, muscle loss, and even cancer.

"If you're aging and you have metabolic disorders, this is associated with faster physical decline, cognitive decline, dementia, frailty, chronic fatigue, and higher risk of death," explains David Brenner, MD, president of Sanford Burnham Prebys Medical Discovery Institute in La Jolla. His institute recently established a new Center for Metabolic and Liver Diseases to tackle this growing health crisis.

The good news? You have more control over this process than you might think.

A Silent Epidemic

The medical term is metabolic dysfunction-associated steatotic liver disease, or MASLD for short (formerly known as fatty liver disease). It occurs when fat builds up in the liver of people who don't drink excessive alcohol. The more severe form, called MASH, involves inflammation and scarring that can ultimately lead to cirrhosis, liver cancer, and organ failure.

The statistics are staggering: MASLD affects an estimated 30 percent of American adults and has become the most common liver disorder worldwide. Between 5 and 10 percent have progressed to MASH. Among people with obesity and type 2 diabetes, the rates are even higher—more than 90 percent of obese patients with diabetes have MASH.

For decades, doctors viewed this as primarily a liver problem. That understanding has fundamentally changed.

"MASLD and MASH are not confined to liver pathology but represent systemic metabolic disorders with profound implications across multiple organ systems," explains a 2025 review published in Frontiers in Medicine. Cardiovascular disease—not liver failure—is now recognized as the leading cause of death among patients with MASLD and MASH. The conditions also increase risks of kidney disease, muscle wasting, and cancers of the colon, breast, and pancreas.

Why Age and Metabolism Create a Perfect Storm

Brenner's research revealed something crucial: aging and poor metabolism don't just add up—they multiply each other's effects. In laboratory studies, animals fed a Western-style diet developed some liver fat. Older animals also developed some liver fat. But older animals on a Western diet? They developed severe fat accumulation along with inflammation and scarring.

"You can't affect your age, but you can affect your metabolism," Brenner says. "Therefore, anything you do to improve your metabolism will be involved with more healthy aging."

At the cellular level, aging involves a process called senescence—when cells stop dividing and start secreting inflammatory chemicals. Think of them as cellular zombies: they're not dead, but they're not functioning properly either, and they're actively harming their neighbors.

"Senescent cells accumulate with advancing age, and they drive chronic low-grade inflammation and tissue damage that contribute to many age-related diseases," explains a 2025 study in Cell Death Discovery. This creates a vicious cycle: inflammation from senescent cells worsens metabolic disease, which creates more inflammation, which accelerates aging.

Recent studies examining tissue samples from both middle-aged and elderly adults revealed widespread declines in how cells process fats and generate energy—changes intimately connected to both aging and metabolic disease.

Two New Drugs Offer Hope

Until recently, doctors could only recommend weight loss and lifestyle changes to treat fatty liver disease. That changed dramatically in 2024 and 2025 with the approval of two groundbreaking medications.

In March 2024, the FDA approved resmetirom (Rezdiffra), the first drug specifically for MASH with liver scarring. The medication works by activating thyroid hormone receptors in the liver. In clinical trials, about 26 to 30 percent of patients achieved resolution of liver inflammation without worsening scarring—nearly three times the rate seen with placebo.

Then came an even bigger development. In August 2025, the FDA approved semaglutide (Wegovy)—already famous as a weight-loss drug—for treating MASH with moderate to advanced liver scarring. It became the first drug in its class (called GLP-1 receptor agonists) approved for this purpose.

The results from the ESSENCE trial were remarkable: 63 percent of patients taking semaglutide saw their liver inflammation resolve without scarring getting worse, compared to just 34 percent taking placebo. Even more encouraging, 37 percent showed actual reversal of liver scarring.

"This is a watershed moment in the field of liver disease, as we can confidently reverse scarring due to MASH," says Rohit Loomba, MD, a hepatology expert involved in the trials.

The advantage of semaglutide extends beyond the liver. Patients lost an average of 13 percent of their body weight, and the drug has already proven to reduce heart attacks and strokes in people with cardiovascular disease—crucial because heart disease kills more MASH patients than liver failure does.

"Wegovy is one of the most widely known and prescribed therapies for obesity and diabetes. This new approval extends that influence to liver health," says Grace L. Su, MD, president of the American Association for the Study of Liver Diseases. "It integrates liver health into overall wellness."

The Diet That Helps You Live to 100

While new drugs offer powerful tools, researchers emphasize that lifestyle remains the foundation of healthy aging. And one dietary pattern keeps showing up in longevity research: the Mediterranean diet.

Scientists studying centenarians in Sicily's mountain villages found something striking. These people who lived past 100 ate lots of vegetables, fruits, whole grains, and olive oil, with minimal red meat and refined carbohydrates. One key feature? Their meals barely raised blood sugar levels—a sharp contrast to the typical American diet heavy in white bread, sugary foods, and processed carbohydrates.

This matters because blood sugar spikes damage blood vessels and organs over time, accelerating aging. The low-glycemic Mediterranean diet helps prevent diabetes and protects against heart disease—two major threats to longevity.

But it's not just what these long-lived Sicilians ate. "The Mediterranean diet comprises not only nutritional factors but also lifestyle characteristics such as social engagement, physical activity, adequate rest, and culinary activities," researchers note. In other words, cooking and sharing meals with family and friends may be just as important as the food itself.

Large clinical trials back this up. The PREDIMED study found that people following a Mediterranean diet supplemented with olive oil reduced their diabetes risk by 35 percent. Other research shows the diet lowers risk of heart disease, stroke, cognitive decline, and even certain cancers.

"If we were to pick one diet, I think Mediterranean would be the easiest one and it's totally doable in San Diego because we can get good sources of fish and seafood and olive oil," notes Rohit Loomba, who directs a liver disease study with 800 participants.

The research even identified specific pathways: reducing animal protein intake may lower levels of IGF-1, a hormone linked to aging, and calm down mTOR, a cellular pathway that, when overactive, accelerates aging.

Personalized Medicine on the Horizon

Scientists at Sanford Burnham Prebys are developing ways to test treatments on miniature versions of patients' livers grown in the lab. These "organoids" are created from tissue that couldn't be used for transplants, offering a way to predict how individual patients will respond to drugs before actually taking them.

"We can reconstruct the liver in three-dimensional conditions in the petri dish and test how efficient a drug will be for that specific patient," explains Tatiana Kisseleva, MD, PhD, an associate professor at the institute.

The center's researchers are also hunting for early warning signs—biomarkers that could detect metabolic disorders and liver cancer when they're still easy to treat. They're studying how the liver, heart, kidneys, and immune system communicate, looking for signals that things are going wrong before symptoms appear.

Meanwhile, doctors are learning to tailor treatments to individual patients. "A GLP-1 drug like semaglutide may be more appropriate for patients with obesity or diabetes, while resmetirom may be better for patients with more advanced liver disease," explains one clinical expert.

More treatments are coming. Several promising drugs are in late-stage clinical trials, targeting different aspects of liver disease through various biological mechanisms. The field is moving from having no approved treatments just two years ago to potentially having multiple options that can be combined for maximum benefit.

Attacking Aging at Its Root

Perhaps most exciting, scientists are developing drugs that target the aging process itself. Remember those "zombie cells" that accumulate as we age? Two types of experimental drugs are showing promise:

Senolytics work like targeted assassins, selectively killing senescent cells while leaving healthy cells alone. By clearing out the troublemakers, these drugs could potentially reduce chronic inflammation and restore tissue function.

Senomorphics take a different approach—they don't kill senescent cells but rather shut down the harmful chemicals they produce. Think of it like muting a group of loud neighbors rather than evicting them.

Both strategies are moving toward clinical trials for conditions ranging from lung disease and arthritis to Alzheimer's and cancer. Researchers are engineering smarter versions that activate only in senescent cells or use antibodies to deliver drugs precisely where needed.

"This dual-pronged approach is being actively explored in preclinical models, especially for chemotherapy-induced aging, metabolic dysfunction, and brain inflammation," notes a 2025 review in Biomedicines.

A Race Against Time—and Demographics

The urgency couldn't be clearer. By 2050, the global population aged 60 and older will nearly double, from 12 percent to 22 percent. With advancing age comes dramatically higher rates of diabetes, fatty liver disease, high blood pressure, and elevated cholesterol—conditions that amplify each other's damage.

Yet this demographic shift also presents opportunity. Michael Karin, PhD, who joined Sanford Burnham Prebys in June 2025 to direct the metabolic and liver diseases center, brings four decades of expertise studying how chronic inflammation promotes cancer. With more than 360,000 citations of his work, he's now focused on preventing and intercepting fatty liver disease before it causes irreversible damage.

"While my new colleagues continue cutting-edge research on the causes of MASLD, I am looking forward to the initiation of novel efforts toward the prevention and interception of MASLD and its more severe complications," Karin says.

The pipeline of experimental therapies continues to expand. Denifanstat, a drug that blocks fat production in the liver, achieved significantly better results than placebo in Phase 2 trials and has been granted Breakthrough Therapy status by the FDA. Several other candidates targeting different biological pathways are in Phase 3 testing.

"These developments signal the beginning of a transformative era in MASH treatment, where patients may soon benefit from a diverse portfolio of targeted therapies designed to halt or even reverse disease progression," wrote researchers in a 2025 review.

What You Can Do Now

The research delivers a clear message: metabolic health and healthy aging are inseparable. Fatty liver disease and related metabolic disorders create a dangerous downward spiral that accelerates aging throughout the body. But the science also offers hope—and concrete actions you can take.

"You can't affect your age, but you can affect your metabolism," Brenner emphasizes. "Anything you do to improve your metabolism will be involved with more healthy aging."

That means:

• Maintain a healthy weight, particularly avoiding excess fat around the middle
• Follow a Mediterranean-style diet rich in vegetables, fruits, whole grains, fish, and olive oil
• Exercise regularly, including both cardio and strength training (but don't overdo it—moderation is key)
• Get screened if you're at risk—simple blood tests can detect early liver problems
• Stay socially connected—loneliness accelerates aging

For those already diagnosed with fatty liver disease or MASH, the landscape has changed dramatically. Two approved medications can now reverse liver damage, with more treatments on the way. Researchers are developing blood tests that could catch problems years earlier and personalized approaches that match each patient with the most effective therapy.

Perhaps most exciting, scientists are learning to attack aging itself—not just treating its consequences, but slowing the fundamental processes that make us grow old.

The twin challenges of an aging population and an epidemic of metabolic disease may seem daunting. But as research accelerates and new treatments emerge, one principle has never been clearer: the choices you make today about diet, exercise, and metabolic health profoundly shape not just how long you'll live, but how well you'll live.

Your liver, it turns out, may hold the key to your golden years.

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