by Siim Land
IGF-1 can protect cells against oxidative stress, which will prevent cell death and can protect against disease. However, if the person’s already sick and has cancer, then IGF-1 will also prevent cancer cells from dying in chemotherapy.
IGF-1 and Aging
IGF-1 receptor signaling is thought to contribute a lot to biological aging and expected lifespan. Studies in roundworms show how genetically mutating the encoding of IGF-1R nearly doubles their lifespan[361]. IGF-1 inhibition also extends lifespan in mice. However, evidence in mammals is not clear and the results are inconsistent in humans.
Lower protein intake is associated with less IGF-1, a reduction in cancer and mortality rates in 65-year-olds and younger but not older people[362].
Both high, as well as low levels of IGF-1, are associated with cancer mortality in older men[363]. The same applies to the risk of dying from all causes. In fact, a meta-analysis of 12 studies with over 14 000 participants found that people with low IGF-1 were at a 1.27x risk of dying and those with higher levels were at a 1.18x risk. Lower levels of IGF-1 may actually be more detrimental as you age because you’ll be more predisposed to muscle loss and bone fractures. Studies find an association with low IGF-1 and sarcopenia in older people[364].
The association of IGF-1 and mortality follows a U-shaped curve with both too high and too low levels of IGF-1 are linked to increased mortality risk[365] (See Figure 50). IGF-1 improves the quality of life by strengthening your bones and promoting muscle growth.
Figure 50 Both low as well as high levels of IGF-1 increase mortality rates
IGF-1 is correlated with longer telomere length which is an important predictor of longevity[366]. That’s why there’s this dichotomy between having enough IGF-1 for muscle and cellular maintenance VS not dying to the proliferation of cancerous tumors.
Furthermore, IGF-1 has many benefits on cognition and brain functioning. Administrating neurotrophic proteins of IGF-1 may potentially reverse the degeneration of spinal cord motor neuron axons[367]. IGF-1 helps to prevent cognitive decline by promoting new brain cell growth in rats[368]. It also improves learning and memory. In older men, it increases mental processing[369]. IGF-1 has anti-depressant and anti-anxiety effects.
IGF-1 prevents the accumulation of amyloid plaques associated with Alzheimer’s disease in rats[370]. People with lower IGF-1 are more likely to have dementia and symptoms of cognitive decline.
IGF-1 deficiencies are linked to different types of growth failures such as dwarfism, and growth retardation. On the flip side, excess growth hormone production causes acromegaly or gigantism that leads to dysfunctional and excessive growth.
IGF-1 is also critical for healing and recovery. People with chronic inflammation tend to have lower IGF-1[371]. When IGF-1 is low inflammation tends to increase due to inadequate antioxidant and repair processes. IGF-1 stimulates collagen synthesis and prevents aging of the skin. However, too much IGF-1 and mTOR may cause acne and rashes.
In healthy individuals, IGF-1 expression would be balanced by the IGF-1 binding protein (IGFBP), which blocks IGF-1s effects. That’s why IGF-1 is bad only if you have too much free serum IGF-1 in the blood. This may happen because the person is being more anabolic than their body needs to be whether due to sedentary living, eating too many calories, not doing proper resistance training, or some other metabolic mismatch.
That’s why it’s not black and white with IGF-1. You want to make sure you express IGF-1 at the right time in the right places, such as your brain cells, muscles, and bone matrix instead of fat cells, amyloid plaques, and malignant cells.
If you’re not predisposed to some sort of a disease and you don’t have cancer, then you don’t have much to worry about dying from having too much IGF-1. Elevating IGF-1 above a safe limit is also very difficult unless you’re taking growth hormone supplements, anabolic steroids, you have insulin resistance or you’re eating copious amounts of excess protein.
IGF-1 is associated with greater risk of mortality and accelerated aging but at the same time IGF-1 helps to prevent those things and supports quality healthspan.
How to Inhibit IGF-1
You would still want to know how to inhibit IGF-1 just for the sake of being able to manipulate your body’s anabolic and catabolic cycles.
Caloric restriction and intermittent fasting can help to reduce cancer development, protect against cognitive decline, reverse diabetes and slow down aging. By now you shouldn’t be surprised by the benefits of fasting.
Intense walking affects serum IGF-1 and IGFBP3[372]. This is probably because physical movement helps to lower insulin and blood glucose, thus lowering IGF-1 as well.
Curcumin lowers IGF-1[373] by activating AMPK and autophagy.
Luteolin inhibits proliferation of breast cancer cells induced by IGF-1[374]. It’s a polyphenol and flavonoid that stimulates AMPK.
EGCG from green tea inhibits IGF-1 stimulated lung cancer[375]. Another polyphenol in action.
Limiting your protein and animal foods can also lower your IGF-1 levels but it may happen at the expense of other fat-soluble vitamins and minerals found from animal foods. Furthermore, chronic protein and mineral deficiencies will accelerate aging again by making you lose muscle and bone strength. That’s why the most cost-effective way to lower IGF-1 again is to do intermittent fasting. You’ll get a bigger effect with fewer long-term side-effects.
How to Increase IGF-1
In case you want to promote anabolism and cellular growth, here’s how to increase IGF-1 levels. Let’s start with some foods and supplements:
Deer antler spray extract is said to contain IGF-1 and promote the production of testosterone.
Red meat, dairy products, and dietary calcium are associated with higher IGF-1.
Dietary fat and carbohydrates raise IGF-1 and lower IGF-1 binding proteins.
DHEA is an endogenous steroid hormone that supports muscle strength and IGF-1.
Leucine and its by-product HMB supplementation increase growth hormone, muscle growth, and IGF-1.
Low zinc causes low IGF-1 as it’s thought zinc potentiates IGF-1 actions.
Selenium and magnesium are associated with total IGF-1.
However, IGF-1 is poorly absorbed by the intestines because of being broken down very rapidly in the gut. That’s why you should focus on increasing IGF-1 through other means as well.
Resistance training increases the bioavailability of IGF-1 and supports bone density, especially in older people.
Sauna sessions can also boost growth hormone and thus increase IGF-1. In fact, growth hormone may rise by 140% immediately after a sauna session[376].
When we return to the possibility of getting cancer from too much IGF-1, then it’s safer to still primarily prime your body’s growth hormone and strengthening pathways with exercise and fasting. These things are all linked to lower risk of mortality so it’s your safest bet.
Whatever the case may be, for both optimal health, longevity, muscle growth, and performance, you want to balance IGF-1 and know how to cycle it.
Based on current research and understanding human physiology, you can say that the best range for IGF-1 is somewhere in the middle wherein you’re not constantly under the effects of IGF-1 but you’re not suffering from its absence either.
The best takeaway is that you want to keep IGF-1 relatively low and suppressed most of the time and activate it in only specific situations wherein the growth effects will contribute to your longevity by supporting muscle hypertrophy and cellular repair. That’s why I’m practicing both intermittent fasting and resistance training. It’s going to boost natural growth hormone production while giving me the other life extension benefits.
Chapter VII
Starting with Strength
“No citizen has a right to be an amateur in the matter of physical training.
What a disgrace it is for a man to grow old
without ever seeing the beauty and strength of which his body is capable.”
&nb
sp; Socrates
Although Metabolic Autophagy is mostly regulated by nutrition and diet, physical exercise and resistance training are equally as important. Building quality muscle and maintaining its function is essential for performance and longevity. In fact, you would probably live a very healthy and long life if you ignored all the nutritional advice in this book but kept lifting weights.
It’s important to be actively engaged with some form of resistance training and other means of exercise because it’s one of the most effective ways of squaring the curve. Furthermore, it’s required to keep the signal of beneficial anabolism alive that would make the nutrients we eat partitioned more appropriately.
In this chapter, I’m going delve into the world of muscle building with strength training and resistance exercise.
Starting with Strength
Strength is the creation of muscular activation initiated by the nervous system. It’s the ability of a given muscle to generate muscular force under specific conditions against a load or resistance.
The more muscle we have the higher our Total Daily Energy Expenditure (TDEE) will be because of the expensive cost of maintaining that tissue. It will also boost our metabolism and promote longevity through other means.
The body will by default always try to avoid putting on more muscle because of the high cost of maintenance. However, in our current contemporary environment, we’re actually better off with more muscle than in the past when food was scarce. At the moment, calories are more than abundant and we have the possibility to become more muscular and healthier (so long as we don’t add excess fat in the process of building muscle).
Building new tissue is an anabolic process that needs to be facilitated in some way. The first and most important thing is an adequate stimulus that creates the necessity for adaptation. Once we’re facing the struggling situation of having to move a heavy object in any given direction, we’re causing our muscle fibers to contract at an appropriate intensity according to the demand. The body then recognizes the need to build more muscle fibers so that we would be able to recruit more of them and do it more efficiently in the future.
Muscle hypertrophy is a phenomenon that increases the size of skeletal muscle by enhancing and growing its cells. The two contributing factors are sarcoplasmic hypertrophy and myofibrillar hypertrophy.
Sarcoplasmic hypertrophy focuses on increasing muscle glycogen storage. It increases the volume of sarcoplasmic fluid in the muscle cells and isn’t accompanied by significant strength gain. The amount of potential blood being stored in the muscles increases. This is the bodybuilder approach. As much size as possible. It’s caused by several sets of 8-12 reps against a submaximal load.
Myofibrillar hypertrophy increases the number of proteins necessary for adding muscular strength and will also cause small enhancements in size. This is the Olympic weightlifter and gymnast approach – as much strength with the least amount of weight. It’s caused by muscle contractions against 80-90% of the one-repetition maximum for 2-6 reps.
Figure 516 Different types of hypertrophy
Size doesn’t necessarily mean more strength and vice versa. They can be built separately, as powerlifters are definitely a lot stronger than bodybuilders despite not being as bulky or with as big muscles.
Muscle growth is facilitated by mTOR and it’s down-stream pathways like Akt/mTORC1/p70S6K etc. When activated, mTOR signals the body to increase protein synthesis and gain size. When it’s inhibited, muscle protein synthesis shuts down, eventually leading to muscle loss. The ratio between these two anabolic and catabolic states dictates whether we build or lose muscle.
The anabolic cycle has two stages. Firstly, we’re stimulating growth that puts us in a catabolic state whether through training or intermittent fasting. Secondly, the effects get finalized, which leads to adaptation. Muscle and strength gain requires both of these steps and happens under the following conditions.
There is adequate stimulus that forces the body to respond. This way the nervous system recognizes the necessity for proper adaptation to the stress encountered in the given environment. Too much, however, will lead to burnout and is difficult to recover from.
Hormones and pathways that stimulate growth are met. Testosterone, HGH, IGF-1, mTOR are one of the more important ones for cellular repair and augmentation.
Protein synthesis is necessary for new tissue to be created. With no building blocks to be found, we won’t be able to construct anything.
Energy is the last condition, as all of this requires calories. Under some rare conditions, the energy can be derived from the body’s own fat store. But for optimal results, we want to help the process as much as possible with quality nutrition.
Even though sarcoplasmic hypertrophy can be created with no significant strength gain, we should still focus on building strength. Myofibrillar hypertrophy trains our nervous system as much as it does our muscles.
Strength determines the quality and quantity of our life. If you’re stronger, you’ll definitely be happier than if you were weaker. Having stronger muscles will make everything easier.
Constant growth and development resemble the essence of life itself. The Greek tale about Milo is the first story about the principles of strength training. Milo lifted a calf every day. As the calf grew larger, Milo also got stronger.
Figure 52 How Milo got strong
That’s how we’re supposed to train as well. We start from the level we’re at, use proper form with our exercises and add a little bit of more resistance, as we get stronger. That’s the secret to building natural muscle and strength.
Training Principles
The key to building muscle and burning fat isn’t in doing hours of light or moderate aerobic exercise. Have you ever seen the difference between a sprinter and a marathon runner? The sprinter recruits a lot more type IIb muscle fibers, which are primarily linked to muscle hypertrophy[377] whereas the endurance athlete trains for only type I fibers.
Long distance runners have a specific look to them because they’re training certain muscle fibers and energy systems that elicit that kind of a hypertrophic response. Marathoners are generally much skinnier and less muscular than sprinters because (1) they don’t train a lot of fast twitch muscles and (2) their sport prefers endurance based adaptations that include having less body weight.
Figure 53 Difference between sprinters and runners
Unfortunately, as Confucious said, the man who chases two rabbits catches none. Doing cardio alongside resistance training decreases the positive effects of both. Concurrent strength and endurance training decrease gains in cardiorespiratory fitness, explosiveness, strength and muscle mass[378]. That’s why it’s not necessarily a good idea to combine a bunch of endurance exercises with hypertrophic ones. You can do your endurance work and aerobics as much as you like. However, whenever you’re doing resistance training to stimulate muscle growth you have to focus on primarily power and strength.
To create physical motion and contraction the body uses motor units, which are composed of a motor neuron and all of the muscle fibers that it supplies. One single motor unit can connect with many different fibers within a muscle, but only innervates one of the three types.
These motor units are on a similar spectrum as muscle fiber types. At one end we have low threshold motor units (LTMUs), which correspond with type I slow twitch fibers, and at the other high threshold motor units (HTMUs), that correspond with type IIb fast twitch fibers. Type IIa falls somewhere in the middle. Both of them get activated according to the force that’s required to move an object. LTMUs for small power, such as lifting a cup, and HTMUs when the resistance is high, such as a near maximum deadlift.
Whether your activating LTMUs or HTMUs dictates the hypertrophy response and training adaptation you’re creating. They can all be laid on a spectrum, which can be used as a guideline for the results you’re after.
Variable
Strength
Power
Hypertrop
hy
Endurance
Load (% of 1RM)
80-100
70-100
60-80
40-60
Repetitions per set
1-5
1-5
8-15
25-60
Sets per exercise
4-7
3-5
4-8
2-4
Rest between sets (mins)
2-6
2-6
1-3
1-2
Duration (secs per set)
5-10
4-8
20-60
80-150
Speed per rep (% of max)
60-100
90-100
60-90
6-80
At near max effort, LTMUs are active along with HTMUs as well. This means, that to gain strength and cause hypertrophic adaptations, we want to be using heavy resistance and high intensity. You’d want to be recruiting as much muscle fibers and neurons as possible.
The 3 main variables of effective training you should know about are:
Volume – the total quantity of movement performed during each exercise, training session and training cycle.
Intensity – the amount of load, weight lifted, speed attained. Intensity is the qualitative component of training. It’s about doing more work per unit of time.
Frequency – the amount of density, how often you train, how many times per week you execute certain movements. This is another quantitative aspect but it is more concerned with recovery.