What is rapamycin?

One of the most intriguing things is the has arisen over the last several years is lifespan extending potential of a substance known as Rapamycin.  Rapamycin is chemotherapy agent, that when used properly, has been shown life extending properties in yeast, flies, worms , mice, and dogs.  No substance in the history of mankind has shown an ability to extend any mammalian life span by almost 25% across the board.

Not only does Rapamycin extend lifespan in mammalian cells, but it may have a significant role in prevention of chronic disease.  By inhibiting the mTOR protein complex, it appears to play a crucial role in the prevention of chronic diseases such as diabetes, cancer, neurological disease and possibly stroke  One other significant role is it maybe the best option for ApoE4 carriers for prevention of Alzheimer’s disease(AD).  This is a real game changer for those who are left with very few effective options to combat this real problem of AD related neurodegeneration.

The History of Rapamycin

Rapamycin was isolated from a bacteria found on Easter Island (Rapa Nui) by Dr. Suren Seghal of McGill University in 1972.  The local barefoot population were resistant to the tetanus bacteria in the soil. He discovered that the bacteria that had an antifungal property. Further research showed not only antifungal properties but antineoplastic activities as well  (Seghal’s story is intriguing.  His last words before death, were even more interesting). There was a tepid amount of excitement, and in the next few decades it was turned into chemotherapy agent.  Rapamune was founded.

However much with other aspects in medicine, the exact mechanism of Rapamycin was elusive. This changed in 1991, when Dr. Michael Hall’s team at the at the University of Basel in Switzerland discovered a protein that regulates cell growth, size and division.  His group discovered that the protein could be inhibited by Rapamycin. The creative name of TOR was given to this complex of proteins (Target Of Rapamycin). TOR was found in all cells and was found in all cells, and found to be a central point in cell growth and maturation.  He also discovered that feeding this complex, made it grow it and made the cells grow larger and older, faster.  Rapamycin was found to inhibit this complex.  Since maturation could be controlled, aging could be controlled.  Not only that, Hall theorized that it could be used to delay the onset of chronic disease and cancer.  Today, it’s a big target of on going research.

A.G.E - Advanced Glycation End products

One of the key concepts in longevity is the effect of cooked food on your body.  When we cook food (over 300 F) we release toxins. For anyone who is concerned about longevity, this is a key concept that they must be familiar with.  

Advanced Glycation End Products or AGE’s are toxins released by food that is heated to >300F by frying, grilling, broiling, and baking.   AGE’s are cancerous ( ex, breast, prostate ) increase risk for complications with diabetes, and are a major cause of chronic inflammation and neurodegeneration in Alzheimer’s.  Browning meats is a major culprit (aka the Maillard reaction)  and can result in extremely high levels of AGE’s (fried bacon tends to make a lot of it). For a complete list please see the following page.

Why is this not commonly addressed?  Consider the fact that cooking food is a major industry and involves the majority of foods out there.  It will take a major cultural shift to make people aware, as practically speaking, a lot of the food we eat regular will be called into question.  While I am not about to give up my BBQ ribs or pulled pork just yet, this concept must be given some serious thought.

MtoR Inhibitors

Rapamycin is arguably the most effective way of inhibiting mTOR, but by no means is it the only one.  Others are there. Some of the major ones are:

Metformin - Indirect inhibitor of mTOR.  It’s been around forever.  its’ weight loss properties have been known for decades. Cancer protective?  Very, very possible . But as an anti-aging drug, just how powerful its it? Try this one on.  In one landmark study, taking metformin made diabetics live longer than their age matched non diabetic cohort.  That suggests that diabetics who take their metformin will likely outlive someone who is their age and is healthy.  (Think what metformin might do for healthy people)

Cialis - one of my long time favourite meds.  I call it the multivitamin for men. The wunderkind drug for the modern men has already shown benefits for erectile dysfunction, BPH, Alzheimer’s, cancer therapeutics, cardiac health, diabetic mortality, improved couple relationships, stem cell protection etc.  Indirectly it also inhibits mTOR and upregulates the sirtuin pathway. Every aging guy needs to strongly consider adding daily low dose cialis to his regimen.

Aspirin - Most realise that aspirin has been often been considered as something that could be used in prevention of heart disease or colon cancer.  Its should be of no surprise that aspirin is an inhibitor of mTOR.  Also, it is also upregulates the sirtuin pathway as well.

Statins - the necessary evil everyone loves to hate.  Regardless of your position on it, it there is a lot of data that suggests you will live longer if you are on it (1), (2), (3), (4), (5), (6), (7)

BP Meds - disruption of the angiotensin II system has been shown to upregulate the sirtuin pathway.  Worth noting for some. These are not my preference due to known side effects.

Mtor pathway

Of the anti-aging pathways, this is arguably the most important. The pathway is based on the presence of a large protein complex (mammalian Target Of Rapamycin)that is regulated by Rapamycin.  It is a central point of the growth process.  When speaking of aging and related chronic disease, suppressing mTOR delays can delay the onset of chronic disease and extend lifespans. There are a few things other things out there that can decrease mTOR, such as Metformin, daily cialis and other meds.  Please see the mTOR inhibitors section for further detail.

sirtuin Pathway

The sirtuin pathway consists of seven small protein complexes that can affect the aging process.  Where as the goal with the mTOR pathway for aging is to inhibit mTOR, sirtuins need to be upregulated (increased) for lifespan benefit.  There are many things that increase Sirtuins, such as NAD+ (1), DHA  from fish oil etc.

Optimized Health, Rapamycin & Alzheimer’s - it’s worth thinking about

People with Alzheimer’s Disease (AD) face a daunting challenge.  In the last 50yrs very little has been made in headway towards treating Alzheimer’s.  There is still no “ cure” Everyone is looking for a “new magic Pill”, and nothing has come to fruition. The US spends excess of a billion dollars a year treating AD, and it’s not helping since the Alzheimer's population is expected to grow from 5 to 13 million in the US.  If any of these meds are worth their salt, these numbers would not be so staggering.

Alzheirmers has been labeled as diabetes of the brain.  I tend to agree with this. When speaking with Dr. Dale Bredesen  - one of the world’s foremost AD researchers - his contention is that much like diabetes, there is no single silver bullet that exists.  His theory revolves around the swiss cheese idea; that there are many holes to plug up, each hole is different. When you optimize, as he suggests in his initial 31 point plan - it’s now much higher - there is actually an improvement in brain volume, in the affected parts of the brain.  I find his theory somewhat interesting since “optimizing” health has been a buzz word for the age management and the anti aging communities  for almost 2 decades. Dale finally added some much needed legitimation to “optimize” and proved that you could reverse cognitive decline by cleaning up the body.

One problem with this theory.  You are demanding from people who have poor memory to implement a 30 + program into their life, or at least have a caregiver give it to them.  Indefinitely. Now a few might succeed, but after attempting the practice with a few patients, its is one of the toughest things to do. I have seen improvements and considering the alternatives, anyone involved with AD should be familiar with his work.

A new player has entered the game:  Rapamycin: in a landmark 2015 study transgenic mice were given the human apoe4 gene.  Rapamycin stopped the workings of the gene to prevent AD.  Thus, is the inhibiting mtor for AD a good idea? Is it time for a human trial? The answer is obviously yes.

But this brings up the age old conundrum of waiting for a human trial to prove absolute efficacy vs the harm in trying it now.  Unfortunately for people who have Alzheirmer’s in their future, the luxury of waiting may mean only certainty of disease earlier.

While these few studies show rapamycin showing benefit with APOE4, it is likely that there is benefit for non APOE4 AD patients as well.  Regardless of who needs it more (non-APOE4 carriers have a lifetime AD risk of 9%, and mean age at diagnosis of 85 years; APOE4 carriers have a lifetime AD risk of 29% and mean age at diagnosis of 75 years), it is in no one’s best interest to discriminate here.