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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 to extend the life span of  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.

Biochemical Pathways

mTOR

Of the anti-aging pathways , this is arguably the most important.

The pathway is based on the presence of a large protein complex that is affected by Rapamycin.  It is a central point of the growth process. When speaking of aging and related chronic disease, when mTOR is suppressed, there is a delay in the onset of chronic disease and extend the lifespan. There are a few things other things out there that can decrease mTOR, such as a common diabetes drug, daily ED pill and other meds.  Please see the mTOR inhibitors section for further detail.

Sirtuin

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, sirutins need to be upregulated (increased) for lifespan benefit.  There are many things that increase Sirtuins, such as NAD+ (1), DHA  from fish oil etc.

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

The daily diabetes drug that starts with an M - 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 this med made diabetics live longer than their age matched non diabetic cohort.  That suggests that diabetics who took this med will likely outlive someone who is their age and is healthy.  (Think what this med might do for healthy people)

Daily ED pill - 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, improves 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 ED pill 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 up-regulate the sirtuin pathway.  Worth noting for some. These are not my preference due to known side effects

Calorie Restriction

There are 4 major diet categories:

• Gaining weight

• Losing weight

• Specialty

• Maintenance

Maintenance diets will always be the most focused on since this is the plan where people will spend most of their lives on . It should be sustainable and should be supportive of long term health

It’s quite well documented for close  to 100 years, that caloric restriction will make you live longer.  Modern diets, regardless of what they are have many variations of this theme  ex Keto, Vegan, Carnivore, Intermittent Fasting, etc. Regardless of how you spin these diets they all ending up restricting calories.  All of them also in one form or another minimize or eliminate sugar and trans-fatty acids. The important point is for people to choose the regimen that is the most sustainable for them.

A.G.E - advanced Glycation endproducts

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 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 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 ribs or pulled pork just yet, this concept must be given some serious thought.

Aa pathway 1 (mtor)

Of the anti-aging pathways , this is arguably the most important

The pathway is based on the presence of a large protein complex that is affected by Rapamycin.  It is a central point of the growth process. When speaking of aging, the more we can suppress mTOR, the longer we can delay the chronic diseases of aging, and extend the lifespan. There are a few things other things out there that can decrease mTOR, such as daily diabetes med that begins with an M, and other meds.  Please see the mTOR inhibitors section for further detail.

Aa pathway 2 (sirtuin)

Sirtuin

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, sirutins 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 (AD) Alzheimer’s Disease 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.

Age and hca

For anyone who is concerned about longevity, one of the key concepts that people must be famililar with is advanced glycation end products.  Quite simply these are part of cooked foods that increased when frying, grilling, broiling, and baking.

AGE’s are cancerous (ex breast, prostate) and cause chronic inflammation.  Its seems to be that high dry heat is the cause of these toxins. Browning meats or baked goods  (aka the Maillard reaction) can result in extremely (high levels) of AGE’s (fried bacon  - real bad). For a complete list please see the following page

Not to be outdone, heterocyclic amines are genotoxic.high temperature, deep frying, and overcooking meats, have the highest levels.  They increase risk of most GI based cancers, lung, breast - alot-, and prostate.

Practically speaking, this can be very restrictive.  However, if longevity is major concern, minimizing of these two toxins must be given some serious thought.