When it comes to longevity drugs, you're sure to ask, because medical science is so advanced, there must be some kind of drug that can help you live longer. Is it just in the variety of health supplements on the market?

Excuse me, Dr. Topol told us bluntly that most of these supplements are an IQ tax. One example, he cited, is fish oil, which is popular with many people. In 2019, the results of a large bedside trial called VITAL were published. Twenty-five thousand and seventy-one extremely healthy adults were tracked by the scientists for more than five years.

The scientists were trying to figure out one thing: eat a standard dose of omega-3 fish oil every day. That is, the kind of fish oil that we can usually buy in the supermarket, which contains the mixture of EPA and DHA, can it keep out cardiovascular diseases and cancer as the legend has it?

It is not valid. It was completely ineffective.

Whether it was the overall incidence of cardiovascular crisis or cancer, there was no significant difference between those who ate fish oil and those who were given a placebo. You think you're doing a deep cleaning of your blood vessels by swallowing that gram of fish oil every day? In fact, what? It's like your house is on fire, and you pour water into the fire with a very small glass of white liquor. What's worse, long-term excessive intake of DHA will reduce the body's immune function and affect platelet aggregation.

Fish oil is a well-established supplement, but what about some of the newest technologies? For example, exchange blood therapy, NAD + supplements, which are popular with Silicon Valley billionaires and longevity clinics. Sounds very sci-fi and high-end.But these methods of "biohacking" either lack evidence of clinical benefit from large randomized controlled trials in humans or come with significant risks, Topol said.Let's start with blood transfusion therapy. You've probably heard of a Silicon Valley billionaire, Brian Johnson, who once swapped his young son's blood in hopes of reversing aging by injecting young blood.

Of course, Johnson himself later admitted that the blood transfusion did not have the desired effect. Although some companies offer young plasma infusions and plasma replacement therapies at prices as high as $10,000 per litre, Topol said. In fact, however, there have been very few studies of blood transfusion in humans, and those studies basically did not find a cure. For example, a small randomized trial of nine Alzheimer's patients, using blood plasma donated by young people, found no effect.

In particular, Topol emphasized that, in addition to their high cost and lack of evidence of efficacy, plasma transfusion and plasma replacement therapy carry a serious risk of disease transmission.

And NAD + supplements. NAD + is a metabolite produced by mitochondria, which plays a central role in energy metabolism: it can promote human gene repair and delay the aging speed of fine cells. As we age, NAD + levels decrease. So many companies began to sell some so-called can re-increase the body's NAD + secretion of "miracle drugs," For example, NR and NMN, one of them is vitamin B3, and the other is an organic small molecule, which will be converted into NAD + after entering the human body, which is also a high-tech blessing of "what to eat."

But Topol says these products are actually being widely sold without being proven in human clinical trials at all. In fact, NAD + works in the body, but also depends on the body's own secretion of many other substances; Simply ingestion of synthetic similar substances from outside the body is likely to be futile. What's even more frightening is that some research institutions and biopharmaceutical companies also deliberately hide its side effects, such as increasing the risk of cancer:

So the question is, what exactly works?

There is one new drug that may be effective, and that is a GLP-1 drug that many people have heard of, such as semaglutide or tirzepatide. These drugs were originally used to treat diabetes and obesity.

How can drugs to treat diabetes and obesity help people live longer? In his book, Tobol makes a disruptive argument that the seemingly disparate and short-lived diseases of heart disease, cancer, and Alzheimer's share a common underlying mechanism: chronic inflammation and immune system dysfunction.

Let's start with heart disease. Conventional wisdom holds that atherosclerosis is when blood vessels are "blocked" by oil, just as water tubes are blocked by dirt. But the essence is inflammation of the walls of blood vessels, and all inflammation is ultimately triggered by our immune system.

Topol spoke of a shocking proof. In a large bedside trial called CANTOS, scientists injected patients with heart diseases with a powerful anti-inflammatory drug (canadumab) that specifically inhibits blood vessel inflammation caused by the immune system. What happened? Not only did the rates of heart attacks drop significantly, but even the incidence of fatal lung cancer was unexpectedly significantly reduced.

You see, this "one stone, two birds" miracle confirms that cardiovascular disease and cancer share the same inflammatory switch.

And then there is cancer. Cancer itself is not usually fatal; what really kills is its "metastasis." The prerequisite for cancer cells to wander and sow in the body is that they must evolve a highly camouflaged ability to evade the aging immune system.

As long as our immune systems remain strong, they can, in the vast majority of cases, lock cancer cells to their roots, Tobol said.

Finally, look at neurodegenerative diseases. In the past, the medical profession thought that the brain, protected by the blood-brain barrier, was an island less affected by the immune system. But now we know that a type of macrophage called microglia resides in the brain, serving as sentries and garbage cleaners to monitor brain health.

However, as we age, these sentinels become depleted and fall into a state of "end-stage inflammation," not only stopping cleaning up the metabolic waste, but instead starting to release pro-inflammatory factors that destroy synaptic synapses and cause brain cells to die.

Tobol is blunt: Without this "inflammatory riot" inside the brain, Alzheimer's and Parkinson's disease would have been hard to really destroy.

Since the root causes of all diseases can be attributed to immune disorders and chronic inflammation, this gives us a promising breakthrough.

These three chronic killers typically take up to two decades or more to lurk and brew, giving humans an extremely wide "early intercept window," Topol said.

So how do we stop it? GLP-1 drugs come in handy: a large randomized trial involving 17,600 obese patients with a history of heart disease showed a 20 percent reduction in the risk of heart attack, stroke and cardiovascular death in the treatment group after three years of using methotrexate. What's even more interesting is that in these patients' bodies, first the risk of inflammation and cardiovascular disease decreased, followed by weight loss.

What does this mean? The underlying logic of GLP-1 saving lives is far more than "physical weight loss makes people healthier," but it leads and independently reduces chronic inflammation throughout the body, thereby reducing cardiovascular risk.

Even more amazing, GLP-1 drugs also show revolutionary potential in the treatment of neurodegenerative diseases. In a bedside trial of patients with early Parkinson disease, the use of GLP-1 successfully prevented the deterioration of motor symptoms in patients with early Parkinson disease, and the protection continued after withdrawal.

This is a big mystery in biology: many macromolecular GLP-1 drugs simply cannot penetrate the blood-brain barrier in large, direct quantities. The scientists speculate that this group of "intestinal hormones" may be using a "remote control" mechanism - they pass through a "gut-brain axis." Signals are sent directly to the cortex and hypothalamus, thus pinning off the "inflammatory riot" that triggers neurodegeneration inside the brain without breaking through the physical barrier.

In other words, the key to treating a terminal illness in the brain is actually in the gut.