Live Longer by Knocking off your Senile Cells

September 23, 2019

References: eBiomedicineNatureNature MedicineNatureCellsMediumNIH ResearchCurr Opin LipidologyCell Stem CellAmer Jr of Physiol.,

We want you to have responsive, alert, available stem cells throughout your body. When in this state, we call them "quiescent". They may be "quiet" but they are geared up and ready to go when called upon. They aren't dividing or multiplying, but are ready to do so if asked. You just might live forever if your cells were always "quiescent". The problem is, they become old, damaged and "senescent" or senile.

That is effectively what aging is. Your cells that are able to divide reach a limit (The Hayflick limit of 50 divisions) and stop dividing. They then undergo a whole raft of changes including changes in chemicals they excrete, signals they send out, structure of their internal architecture, etc. They are still metabolically active and doing their "thing" in the organ they belong to, but they can't divide and they are basically zombies. Like the zombies on horror movies, they can invade you and infect you with their senescence. Transplant senescent cells from old rats to young rats, and the young rats act old. This process is all about the conversation between healthy mitochondria and your nucleus. When that process is humming and healthy, your cells remain responsive and "quiescent". When it degrades, they become "senescent". 

Getting rid of senescent cells would appear to be a crafty little idea of helping you live longer. We do know that ailing organs pile up more and more senescent cells as they become more dysfunctional with whatever their disease state is. So what would happen if we found drugs that could selectively kill off senescent cells? 
That's what this week's news is about. From the Mayo Clinic, researchers report that they can kill off senescent cells selectively with so-called senolytic drugs. Using an herbal supplement called quercetin and a leukemia drug called dasatinib the study authors found remarkable reduction in the senolytic population that persisted for 11 days after stopping the study. In mice that combination has led to mice living longer. Now we know it appears to be safe in humans in short term studies. We don't have long term studies, yet. 

But before you rush out and start yourself on quercetin, remember there are other ways to pull your cranky mitochondria back from middle age senescence to more youthful quiescence. Exercise does it! High-Intensity Training, HIT, is the current hot topic where you go nuts for 4 minutes of hard-driving, sweat-inducing and heart rate raising exercise. It works because.....? It wakes up your senescing mitochondria and cells and pulls them back into quiescence. Got that? Anything else? 

Why yes. Fasting. When you fast, you force your body to switch from glucose burning to ketone or fat burning. That's good for your stem cells and quiesence. In fact, there is increasing evidence that stem cells love your being on ketones. Plain and simple. When you fast, you switch your body into ketone or fat burning (You chop up your fat molecules into ketones once you have burned off all your carbs - usually after about 2 days). That wakes up your middle-aged, sloppy cells on the verge of becoming senescent, and hauls that back into quiescence. What's the proof? Too much to enter here except to reference all the feeding studies like in Madison, WI where rhesus monkies fed 30% fewer calories lived much, much longer than those fed to satiety. We eat to satiety, and then some.

Any way to speed up senescence? Yes, again. A high-fat diet will do that just fine. Radiation, sedentary life, pesticides, or any other oxidative stress you can think up will all do it.

WWW: What will work for me. Wow. Fascinating. We can use drugs to push old, cruddy quiescent cells out and kill them off. Ok, leukemia drugs make me a bit nervous but quercetin is tried and true safe. It's the concept that is reinforcing the over-arching concept. We want to keep our cells quiescent. This is the secret sauce of exercise. And then there is fasting. I'm doing my 5-day thing monthly. Did I mention that boosting your growth hormone will do it too?

Pop Quiz

  1. Can you really live longer by knocking off your senile old cells?                             Answer: Not really proven yet but all the pieces are in place. The longest-lived persons all over the world fit the pattern: they exercise. they fast, they eat less fat
  2. What did the researchers do at Mayo that worked on senescent cells?                         Answer: They showed they could selectively kill them off with two drugs
  3. Why are senescent cells such a big deal?                                      Answer: They are front and center of just about every disease. You die when your burden of senescent cells piles up too high.
  4. Can you recall how much longer men lived in the Retired Men's Study from Honolulu when they walked 2 miles a day?                     Answer: (Bonus points). Double.Nice number.
  5. What are ketones and what do they have to do with senescence?                          Answer: Ketones are the chopped up fat molecules we make when we have burned off all our carbs. You can get a few ketones in your system every day if you don't eat for 13 hours. Longer fasting is better. First, you burn off your 1500 calories of carbs. Then you get to the easy fat hanging out in your fatty liver. Then you plunge ahead and just plain lose weight and wake up all your lazy quiescent cells.