Monthly Archives: October 2019

Senolytic Therapy for Alzheimer’s? “STOP IT IN ITS TRACKS

References: Aging Cell, Forbes MagazineDiabetes,

It’s getting close to Halloween. Zombies are in everyone’s yards. And zombie cells are in you. You have heard about senescence in this column. It happens to good healthy cells that are “quiescent” (waiting and responsive, able to duplicate) when they tip into “senescence”. A senescent cell is a zombie. It is hanging around but unable to be constructive and helpful. Actually, it is harmful because they ooze inflammatory substances and infect their neighbors. But they don’t go away. Aging is all about accumulating more and more senescent cells in all your organs. And we see that in the blood tests with an inexorable decline in circulating stem cells. We have talked about getting rid of senescent cells with various combinations of supplements on your own, or with Mayo Clinic’s protocol of Dasatinib (a leukemia drug) and quercetin, a well-known supplement derived from onions and apples. 
It’s the accumulation of tau proteins in the brain that appears to be the tipping point in Alzheimer’s, and possibly up to 20 other brain disease. Tau proteins are the stabilizing scaffolding of axons, the wires that connect brain cells. If they get misfolded and disorganized, it’s as though your scaffolding on your new building suddenly collapsed. This paper from the University of Texas shows that a link exists between senescent cells and the accumulation of tau proteins. This means you have senescent cells, zombies, in your brain with broken scaffolding that you can’t clear out. It’s not just that the tau proteins are in the way but the zombie cells won’t go away. No matter how many “Trick or Treats” you give them, they just keep infecting the cells around them. No wonder you can’t think straight! What if……what if you could clear out those zombies? Well, you can. 
You can clear senescent cells from mouse brains that are genetically altered to look like human Alzheimer’s. The “senolytic” treatment given the mice was the same used at Mayo, Dasatinib and Quercetin, once every two weeks over 12 weeks. They then did MRI’s on the mouse’s brains and looked at them under a microscope. 
One of the authors was so enthusiastic about their outcome that he was quoted as saying in Forbes, “It stopped Alzheimer’s in its tracks!” That’s pretty intense. Did it cause the mice any harm? Nope. Not that they could detect. Will this work in humans? Who knows! If you had early-onset Alzheimer’s, Parkinson’s…..would you try it?

WWW: What will work for me. This is another classic example of the “ethics” of modern medicine. Is it ethical to take a scientific advance found in mice to you when you are descending into an irreversible disease? If it doesn’t cause harm, that you know of, does that make it easier? Or, do you care if it causes harm? Should this be a therapy used by everyone over 40, as 50% of us are going to get Alzheimer’s someday if we live long enough?

Pop Quiz

  1. It’s Halloween in your brain, what is happening to the zombie cells in your brain? Answer: They are becoming “senescent”
  2. What does senescent mean? Answer: Those cells can’t duplicate anymore but more importantly, they put out inflammatory cytokines that inflame and damage cells around them into becoming senescent.
  3. What appears to be the cardinal marker of ongoing senescence in brain cells? 
    Answer: The accumulation of tau proteins.
  4. n mice, what can you do to clear out those senescent cells? Answer: Dasatinib (chemotherapy drug) and Quercetin, dosed 6 times over 12 weeks.
  5. What else can you do to reverse that senescence? Answer: Walk two miles every day of the world. A bit of sweat is better. Fast mimicking diet if not outright fasting on a routine basis. Growth hormone might also be a secret path.

Prolonged Fasting (10 days) Cures Fatty Liver

References: EMBO Molecular MedicineScience DailyWebMDJ Clin MedEur J GastroJCEM,

If you have gained meaningful weight since you were a teen, and have a waist size 4-6 inches greater than you had before, you likely have fatty liver. If you drink much alcohol, you likely have fatty-liver. That means you join just about 50% of Americans. We all have it. Fatty liver, insulin resistance, diabetes, and big waist size all go hand in hand. In fact, fatty-liver goes hand in hand with SIBO (small intestinal bowel overgrowth), also goes hand in hand, a curious correlation. 
The result of all this is that your liver doesn’t work as efficiently as you would want it to. You have insulin resistance and many other metabolic markers of dysfunction. If you just look at pictures of the endoplasmic reticulum, your body’s metabolic factory where you make critical proteins, you can see that fatty liver just mucks thinks up by making big pools of fat on the factory floor. It’s like parking empty semi-trailers on an assembly line floor – horribly out of context and in the way.

How do you get fatty-liver? Easy. Eating too much stuff that gets turned into fat at a rate so fast you can’t ship it out from your liver. So it backs up. That’s it. Alcohol is a premier example. You instantly make triglycerides and small LDLs in your blood when you drink alcohol and your liver backs up with it if you make more than you can ship to your fat cells. You get a “beer belly” as you keep shipping fat out. That means you are also getting a “beer-liver”. But lots of bread and chips, pretzels and Fritos, bagels and donuts will do it too. Did I mention ice-cream?

GADD45β, (Growth Arrest and DNA Damage-inducible Peptide) appears to be a critical peptide you stop making when you eat or drink too much. It protects you from fatty-liver. Fasting increases its level. There you have it. You can cure your fatty-liver very quickly with a prolonged, 10-day fast. You make more GADD45β. Your liver starts to regenerate and heal itself from the self-induced damage.

Can I explain the sequence of events of what happens to you? Critical to the whole process is turning off insulin, as insulin is the key driver to forcing you to store calories. Part of the storage process is making fat molecules to ship to your fat cells as triglycerides from your liver. Turn off insulin and you turn off the engine driving that process. Sort of like turning off the electricity and your computer printer stops printing. The production of insulin is defined by what you eat. Refined carbs do it best. Any flour will do. But root vegetables, grains, and meat also turn on insulin. Stop eating those foods and your insulin level plummets. The first event in the fasting sequence is turning off insulin, sort of like turning off the electricity. Then, it takes two days to empty your carb reserves when you fast.

By hour 48, you have burned all 1500 calories of carbs that were packed into your muscles and liver as glycogen. You are now in ketosis, meaning you are running on ketones, the breakdown products of fat. You feel differently, sort of like hunger but not really. Your brain feels sharper. You are colder and need an extra sweater. 
Your body is now looking around for calories to burn. First comes the easy to get to tank of fat in your liver. Your fatty liver gets addressed. You start making GADD45β and shipping the fat out to burn. It takes 3-4 days to get rid of that fat, maybe it a bit longer if you have big-time fatty-liver. 
By day 6 or 7, your liver function tests are dramatically better and your blood cholesterol ironically starts to rise. That’s because you are cleaning out the fat from your liver and your arteries. No kidding! Your body needs fuel and that fat is the easy-to-get-to stuff because it’s right there where the blood flows and is access to mobilize. 
Ok, fasting sounds too hard. Traditional methods of treating fatty liver include such advice as “eat less and lose weight”. That hasn’t worked very well because that admonition doesn’t come with recipes of food that don’t turn off insulin. The only foods that don’t turn on insulin are green, above-ground vegetables. Make me a diet of spinach, Brussel’s sprouts, broccoli and kale, and I will get rid of your fatty liver. But you have to eat them only, with a drizzle of olive oil on them and only 800 calories a day. Do that for 4 weeks and your fatty liver will be gone too. Oh heck, just fast for 10 days and get it over with. Come see me and I’ll show you how.

WWW: What will work for me. I’m watching the liver functions of every one of my patients who do 10-day fasts. I’m personally just finished by most recent 5- day fast mimicking diet of 800 calories. I didn’t get hungry, one more time, as my body is now trained to flip into and out of ketosis. It took about 6 months to get there but I’m now quite comfortable getting in and out of it. My liver function tests are now normal and my waist size is back down with two inches of my high school graduation size. It was up over 6 inches from where I am now. Then, I had fatty liver.

Pop Quiz

  1. Who has fatty-liver? Answer: Anyone of us who have gained more than 4-6 inches on our waist sizes since highschool. Hmm: all of us, just about.
  2. What is the cause of fatty liver? Answer: Too much nutrition of fat inducing foods, with a dab of booze on the side.
  3. What’s the best way to get rid of fatty liver? Answer: Stop it. Fast. The fewer the calories, the faster it works. You won’t feel hungry after about day 4-5 but you will feel colder and be more easily fatigued if its the first time you have ever done it.
  4. Can you measure your fatty liver? Answer: Well, yes, with high tech expensive stuff live an MRI or an ultrasound. Better way is your waist size and simply asking if you have gained 6 inches since highschool. Or an SGOT/SGPT liver function tests commonly on the chem panel. GADD45β is really a research tool not on the market for normal folks.
  5. Ok, what’s a more traditional way to get rid of fatty liver? Answer: lose weight more slowly. Takes longer and fails because, because, because. So it doesn’t work very well. This is serious business. Take it seriously. Don’t eat for 10 days. Be a vegan for 7 days before and after. Get lots of help. Read Joel Fuhrman’s book: Fasting Fasting for wellness.