Want to live forever? Factors influencing longevity.
Living a long, vibrant, healthy life is a common goal. But what can we do to extend our health span?
Should we eat more fruit and veggies? Less processed foods? More protein? Less protein? Exercise more? Lose weight? Sleep more? Get more sun? Less blue light?
The numerous facets of health and longevity are complex and above my pay grade. However, I am willing to add my two cents to the discussion in the areas of insulin, blood glucose, fasting and nutrition along with some input from people I respect.
Dr Ted’s top tips
My wise friend Dr Ted Naiman recently commented on the topic of diet for longevity.
I see centenarians at work, and as far as I can tell it is important to be:
– insulin sensitive,
– active, and
– relatively strong
Extreme careful protein restriction? Not so much. I for one will focus on the first three.
Not only is Ted enviably buff, he also has a neat way of condensing wisdom into short bites that are worth unpacking a little further.
Longevity and insulin sensitivity
The leading causes of death in adults in the western world (i.e. heart disease, stroke, cancer, Alzheimer’s and Parkinson’s) all have something in common. They are diseases of modern society, related to metabolic health and exacerbated by excessive insulin and / or high blood glucose levels.
People who live longer still die from these same diseases, they just succumb to them later.
This chart (from Barbieri, 2001) shows that insulin resistance generally deteriorates with age. However if you’re one of the few to make it past 90 then chances are your insulin resistance is pretty spectacular!
Ted’s infographic below explains how insulin resistance and metabolic syndrome leads to hyperinsulinemia (elevated insulin) and hyperglycaemia (elevated blood glucose) and then to heart disease and many of the other diseases of modern society.
And your chance of maintaining a big brain that is free of Alzheimer’s and Parkinson’s (causes of number four and five) seems to be greatly improved if you keep your blood glucose levels low.
We’ll come back to cancer, cause of death number three, a little later.
Longevity and muscle mass
While you might be able to make an argument for longevity diet around restricting protein or even calories based on laboratory experiments, people live in the real world and need adequate strength to move around, stay active and be relatively strong. People who are lean and strong intuitively look healthy and attractive to us.
Longevity research is typically done in yeast, worms, mice or other animals who live protected in captivity. Unfortunately, real people don’t live in protected laboratory environments in a petri dish. We live in the real world where real people break.
Loss of muscle as we age (i.e. sarcopenia) is a major issue. Many older people become brittle and weak. They take a fall, break their hip and never get up. Maintaining strength and lean muscle mass is important.
You don’t see many fat animals in the wild, but at the same time you don’t see skinny animals, unless they are sick. Animals that survive in their natural environment are lean, strong and fast. They have to be to survive, to catch food and avoid being eaten.
Humans in the wild also tend to be strong and lean.
Similar to Ted Naiman, Ian Rambo (pictured below), 62, is a fan of intermittent fasting and a moderate protein diet. Rambo doesn’t look like he’s about to trip and break his hip any time soon.
Longevity and exercise
A lot can be said about exercise, longevity and metabolic health.
Glucose disposal is everything. The best way to get there is by increasing the muscle’s capacity to take up glucose and make glycogen, and that’s best accomplished through lifting heavy weights. Doing so also increases health span (i.e. reducing injuries, lowering pain, and increasing mobility through life).
Exercise depletes the glucose in our blood, liver and muscles and causes us to tap into our fat stores. But it’s more than just about using up energy.
As metabolic health and mitochondrial density improves through exercise, our fat oxidation rate increases. We become metabolically flexible which means that we can easily use glucose or fat for fuel. Once we improve our fitness and insulin sensitivity we get to the point that we can even obtain some of the glucose we need from fat.
My friend Mike Julian commented:
Every triglyceride that is broken down gives up one glycerol molecule. Two glycerol molecules will make one glucose. So the more fat we are capable of burning, the more glucose we can make from fat oxidation, thus the better we get at restoring muscle glycogen without eating carbohydrates.
Also the glycogen that we do burn produces lactate, which is then recycled to make more glucose in the cori cycle, which also contributes to muscle glycogen stores during recovery.
The goal is to increase mitochondrial density so that we are very good at oxidizing fats. When we have poor mitochondrial density we are far more prone to switching over to anaerobic metabolism at low activity levels and anaerobic activities require glucose.
So if we can’t burn fat at high rates due to low numbers of mitochondria, we can’t make much glucose from glycerol via fat oxidation, so in turn our bodies go to plan B which is to make it out of amino acids in order to make up for the rest of what it needs.
So if you increase your mitochondrial density through exercise, you’ll oxidize a higher volume of fat, which will give a higher yield of glucose from glycerol and thus reduce your body’s need to break down aminos from dietary protein and lean mass.
Post exercise increased fat oxidation due to mitochondrial density produces more ketones during the recovery period which get used preferentially so the increased glucose production during that time can go towards refilling of glycogen stores rather than be oxidized for energy. This is why many top keto athletes will fast for a few hours post training. If they eat straight away they miss out on this phenomenon and actually will recover slower.
Longevity and caloric restriction
Building on the prior trials in yeast and worms, the current dietary restriction longevity experiments in rhesus monkeys are looking positive. You can see the monkey on the right who has been living on 30% less calories looks younger and healthier than the monkey on the left who is the same age.
The monkeys who eat less have less age related disease and live longer.
While avoiding excess energy intake is beneficial, there are differing opinions on how this translates to humans in the real world in terms of increased life span.
Peter Attia says:
Most people in this space, the super-in-the-weeds people on this topic that I’ve spoken with at length, do not believe caloric restriction actually enhances survival in the wild.
Nobody disputes that for most species it enhances survival in the laboratory, but once you get into the wild, you’re basically trading one type of mortality for another.
So many things in life are a balance and involve compromise. While you need adequate nutrition to be strong and active, our bodies also age more slowly if we don’t subject ourselves to excess energy.
Another problem with calorie restriction is that unfortunately most of us don’t have the self-discipline to limit our food intake all the time. When we do eat we find it hard to stop until we are satisfied. Our survival instincts don’t know about the studies in the monkeys, the worms and the yeast.
Most people find it hard to maintain constant caloric restriction when they have free will and unlimited access to food. And then the cruel trick for people who do have the discipline to consistently reduce their energy intake is that the body will scale back its energy expenditure to stay within the reduced energy intake.
Longevity and intermittent fasting
“Complete abstinence is easier than perfect moderation.”
So if caloric restriction doesn’t necessarily work, then what’s the solution? Jason Fung makes a compelling case for the benefits of intermittent fasting rather than chronic calorie restriction.
When there is a lack of food a process called autophagy (from the Greek auto, “self” and phagein, “to eat”) kicks in and we turn to our own old cells for nutrients. Autophagy is nature’s way of getting the energy we need when we don’t eat in addition to cleaning out the old junk in our bodies and brains. When we get to eat again we build up new, fresh healthier cells.
But this process of cell clean up and regeneration cannot occur without giving the body the chance to clean out the old cells first. We regenerate and slow aging when we don’t always have a constant supply of energy. One of the advantages of intermittent fasting over simply reducing calories is that you get a deeper cleanse of the old cells with total restriction of energy inputs.
In the video below David Sinclair explains how our body makes a special effort to repair itself when there is a lack of food. In a famine your body senses an emergency and sends out Sirtuin proteins to maximise the health of our mitochondria to increase the chance that you will survive the famine and have the best chance of living until a time when food is more plentiful and you can reproduce and pass on your genes. Unfortunately, this emergency repair function just doesn’t happen when food is plentiful. They’re working on drugs that will mimic this effect, but in the meantime, intermittent fasting is free.
As detailed in the how to use your glucose meter as a fuel gauge article, it can be useful to track blood glucose or weight to help guide the frequency and duration of intermittent fasting to make sure you’re moving towards your goals.
Longevity and protein restriction
Many people hypothesise that restricting protein is an important component to slow aging.
Dr Ron Rosedale talks a lot about the dangers of glycation and the kinase mTOR. His hypothesis, as articulated in the Safe Starches Debate and AHS 2012, is that we should avoid carbohydrates to avoid the dis-benefits of glycation, particularly as we can get the glucose we need from protein and to a lesser extent from fat. When you see that all the major diseases of aging are correlated with high blood sugars and high insulin levels you might think that he is onto something.
In his AHS 2012 talk Rosedale discusses the dangers of mTOR (mammalian target of rapamycin). mTOR is activated when we eat protein and raise insulin and leads to suppression of autophagy. In view of this Rosedale recommends relatively low levels of protein for people with diabetes (e.g. 0.6g/kg) and even lower for people who are battling cancer (e.g. 0.45g/kg).
Vegan luminary Dr Michael Gregor points to the various drawbacks of excess dietary protein and makes a compelling case for restricting animal protein by focusing on plant foods rather than caloric restriction or intermittent fasting.
There’s a fascinating August 2015 paper by Valter Longo et al that gives an overview of the current thinking in longevity. While it mentions protein restriction as a possible area for future investigation, discussion of protein restriction generally seems to be in the context of intermittent restriction with subsequent re-feeding.
To date, very few studies have been performed in humans on the potential beneficial effects of protein and/or amino acid restriction on aging processes or age-associated chronic diseases. 
There are obvious benefits in having periods where the body can clean out old proteins, however you also need high quality nutrition to build back the new shiny parts.
While I have gone to great lengths to bring attention to the fact that protein contributes to the insulin load of the diet, I struggle with the concept of chronic protein avoidance when so many of the things I read talk about the mental health benefits of protein,  the benefits of lean muscle mass for metabolic health, the satiety benefits of protein and the importance of lean muscle as we get older to ensure we can be active and strong rather than brittle.
Like everything though it’s a balancing act. Binging on protein supplements and egg whites to get big and jacked is not going to lead to optimal health and longevity. Some of these guys are even injecting extra insulin for its anabolic hypertrophy effects on top of the anabolic hormones. This is not healthy and not natural.
So how much protein do you need when you do eat? I think you need enough to be strong and active but at the same time without raising insulin and blood sugars and decreasing ketones.
Lean muscle = good
Insulin sensitivity = good
Excess body fat = bad
High insulin = bad
Longevity and cancer
There’s also a growing momentum around the metabolic theory of cancer (the number three leading cause of death) which hypotheses that excess glucose feeds cancer growth and restricting glucose through a therapeutic ketogenic diet with intermittent fasting will reduce your risk of cancer.
When you hear Seyfriend talk he seems very proud of and excited about the glucose : ketone index (GKI) which he developed as a proxy for a person’s insulin levels. As you can see in the chart below, as our blood glucose levels decrease ketone levels rise.
More than blood glucose or ketones alone, the relationship between your blood glucose and ketones seems to be a good proxy for your insulin sensitivity.
It seems that someone with a GKI of less than 10 has fairly low insulin levels, someone with a GKI of less than 3 has excellent metabolic health, while someone battling cancer might want to target a GKI of 1.0.
Reducing the insulin load of your diet can reduce your glucose levels, increase your ketones and reduce your risk of metabolic syndrome and the most prominent causes of death (i.e. heart disease, stroke, cancer, Alzheimer’s and Parkinson’s).
Just to be clear, you people who achieve these excellent insulin resistance levels don’t get get there by simple adding more fat to their morning coffee but through disciplined intermittent fasting which tends to lead to reduction in body fat which improves insulin resistance.
Optimal nutrition for longevity
On one extreme too much food will make us fat and insulin resistant and stop the body from repairing itself.
On the other extreme calorie restriction will make us frail and vulnerable to disease and accidents.
So how do we find the middle ground?
On the topic of carbohydrates Peter Attia says:
You want to consume basically as much glucose as you can tolerate before you start to get out of glucose homeostasis. For me there’s a different number than for the next person, and you have to find what the level is.
I’ve been wearing a continuous glucose monitor for several months now. Every day I just have it spit out my 24-hour average of glucose plus a standard deviation, and I now know my sweet spot. I like to have a 24-hour average of between 91 and 93 mg/dL with a standard deviation less than 10.
We can’t measure insulin in real time. To me, the Holy Grail would be to have an area under the curve of insulin, but this becomes a pretty good proxy.
It’s fascinating to see that Attia, who is a super fit semi pro athlete is going to the effort of wearing a continuous glucose meter full time. CGMs are generally worn by people with type 1 diabetes like my wife.
The process he is describes of reducing dietary glucose intake to a point where blood glucose levels are normalised is essentially the process used by the people we see who are managing type 1 diabetes as well as possible.
The food insulin index testing measured the area under the curve response to various foods (i.e. what Attia describes as the Holy Grail) and has been really useful for us to understand which dietary inputs cause the greatest blood glucose swings and require largest amounts of insulin.
I think the reason that Attia is recommending ‘as much glucose as you can tolerate’ is to fuel your energy needs for activity, maximise nutrition and dietary flexibility. This level of blood glucose control will give him an HbA1c of 4.8% which will put him in the lowest risk category for the most common diseases of aging. But to maintain such a tight standard deviation he’s going to be managing the net carbs and protein in his diet so his blood sugar doesn’t go over 100mg/dL or 5.6mmol/L too often.
Dr Roy Taylor recently released an interesting paper where he proposes that each person has a personal fat threshold. Rather than the BMI chart or body fat, there is a certain level at which the body fat becomes inflamed and insulin resistant which leads to diabetes and all the issues related to metabolic syndrome. What this means in practice is if your blood glucose levels are rising above optimal you need to eat less to lose body fat.
When it comes to protein Attia says:
What I’m telling my patients is really you only need as much protein as is necessary to preserve muscle mass.
You have a sliding scale, which is carbohydrate goes up until you hit your glucose and insulin ceiling, protein comes down until you’re about to erode into muscle mass and slip into positive nitrogen balance, and then fat becomes the delta.
So in somebody like me, that’s probably about 20% carb, 20% protein 60% fat.
I’ve done everything from vegan to full ketogenic. I’ve experimented with the entire spectrum of religions, but nevertheless, that’s the framework.
It’s worth noting here that this quote from Peter is in the context him talking at length about mTOR, ROS, glucose control and protein restriction. Attia is one of the smartest guys in nutrition, medicine and anti-aging science, but he’s not avoiding protein. He’s making sure he gets enough to maintain lean muscle mass but not so much that it messes with his glucose levels or requires a significant glucose response.
Attia also talks about maximising glucose and minimising protein to normalise blood glucose and insulin. Given that the focus is on managing insulin levels, I think you could also take the opposite approach to minimise carbs and maximise protein as much as you can without disrupting glucose or losing ketones. People with type 1 diabetes will tend to consume medium to higher protein levels (which provide glucose but without the same degree of glucose swing) with lower levels of carbohydrates.
Or alternatively find your own balance of net carbs and protein that gives excellent blood glucose levels and some ketones.
When it comes to finding the optimal level of protein and energy Dr Tommy Wood said:
The anti-IGF-1 (insulin like growth factor) crowd confuse me. Lots = bad (cancer). Very little = also bad (sarcopenia and broken hips).
One of the pioneers in the field of longevity is Roy Walford, who developed the concept of Calorie Restriction with Optimal Nutrition (CRON). Many of the ideas in this article and the blog overall are built around Walford’s ideas regarding optimising nutrition for health and longevity.
While Walford lived his theories in practice, he unfortunately died at 79 of ALS so we didn’t really get to find out whether calorie restriction delayed the major diseases of aging for him. The pictures below are taken of Dr Walford before and after two years living in Biosphere 2.
Walford was the crew’s physician and meticulously recorded the health markers of the Biosphere 2 ‘crew members’. It’s interesting to see how markers like the BMI chart, glucose, insulin and HbA1c all improved markedly with the semi-starvation conditions during the experiment, however they reverted to more normal levels after resuming normal eating.
If we are going to fast and / or restrict calories to optimise our metabolic health it’s even more important that we make sure that the food we do eat, when we eat it, provides all the nutrients that we need to thrive and build back new shiny parts of our body. Unfortunately it seems that the optimal nutrition component of Walford’s CRON concept is not discussed much these days.
In the article optimal foods for different goals I have detailed a system that can be tailored to identify nutrient dense foods for different goals to balance nutrient density and insulin load. I hope this will help to spark further discussion around the topic of nutrient density and which foods would be most helpful for different people.
So what is optimal longevity diet?
So what does all this mean? What do we know about maximising our metabolic health and avoiding the primary diseases of aging?
Is too much energy bad… yes.
Is eating all the time bad…. yes.
Is excess protein bad… maybe, maybe not, however the vegans would say that we should avoid animal protein and stick to only plant based foods.
Are excess carbohydrates bad… maybe, maybe not, however the low carb / keto crowd would say that you need to avoid carbohydrates because they raise your insulin.
Is excess protein and excess non-fibre carbohydrates bad… most likely, yes.
Both carbohydrates and protein will raise insulin, blood glucose, IGF-1 and upregulate mTOR which all accelerate aging.
In the end though we have to eat. We are programmed for survival. While not eating too much and intermittent fasting are important considerations, when we do eat though we should maximise the nutrient density and prioritise foods that do not not raise our insulin and blood glucose levels. I think if you get that right a lot of the other things will follow.
There is no perfect dietary solution for all. What is best for you will come down to your situation, goals and preferences.
Some people will prefer zero carb with lots of meat.
Some people feel strongly about avoiding animal products and do well on a plant based diet with minimal processed foods.
Some will aim for a therapeutic ketosis approach to tackle major metabolic issues.
All of these extremes are viable but a balance somewhere in the middle might be easier to maintain in the long term while also maximising the nutrient density of the calories we consume.
What is almost certainly dangerous for most people is the low fat, high insulin load approach that has been recommended for the past few decades and seems to have led to increased consumption of low nutrient density highly processed food products by many.