Trait: Muscle Growth (IGF-1)
Dr Haran Sivapalan
February 17, 2020
What is IGF-1?
IGF-1 stands for Insulin-like Growth Factor 1.
It is a hormone (i.e. a chemical message transmitted in the bloodstream) that stimulates growth of bone, muscle and other tissues in the body.
Accordingly, we can describe IGF-1 as an anabolic hormone: it promotes metabolic reactions that build-up tissue.
IGF-1 is produced by our liver and muscles after exercise, where it stimulates hypertrophy – an increase in muscle volume or mass resulting from a rise in the cross-sectional area of individual muscle fibers.
IGF-1 activity is therefore important for building muscle and improving body composition.
By promoting cell growth and division, IGF-1 also plays a role in ageing – the progressive decline in the biological function of cells.
Finally, IGF-1 also influences the function and sensitivity of our body to insulin. It therefore plays a role in the regulation of fat and sugar metabolism.
- IGF-1 is a hormone that stimulates muscle, bone and tissue growth.
- IGF-1 also has an effect on ageing and insulin function.
How is IGF-1 produced?
Growth hormone and the IGF-1 axis
About 75% of IGF-1 is secreted by our liver in response to another hormone, growth hormone (GH).
As its name suggests, growth hormone promotes the growth and development of cells, especially in childhood. In adults, it plays a role in sugar and fat metabolism, as well in the regulation of muscle mass. Growth hormone is released by a key gland located at the base of our brain: the pituitary gland.
Exercise, sleep and food intake all can trigger the release of growth hormone from the pituitary gland. Once released, growth hormone travels in the bloodstream and acts on the liver, where it stimulates liver cells (called hepatocytes) to produce IGF-1.
IGF-1 produced by the liver then circulates in our bloodstream, where it can act on various target tissues. As such, it is known as circulating IGF-1 (cIGF-1).
Rather than circulating freely in the bloodstream, IGF-1 is bound to one of six specialized proteins called IGF binding proteins (IGFBPs). Of these, IGFBP3 is by the far the most important transporter of IGF-1.
Muscle production of IGF-1
In addition to production by the liver, most other tissues in the body also secrete IGF-1. This includes muscle tissue. As opposed to circulating widely in the bloodstream, IGF-1 secreted by muscle cells (mIGF-1) acts locally on the same (‘auto’) or nearby (para-) muscle tissue. In this sense, we describe IGF-1 as being an autocrine or paracrine growth factor.
- IGF-1 is produced by the liver in response to growth hormone released by the pituitary gland.
- IGF-1 produced by the liver circulates in the bloodstream and binds to target organs.
- Muscles also locally produce IGF-1.
IGF-1 and muscle growth
IGF-1 stimulates the process of hypertrophy – an increase in muscle mass / volume.
As explained in the Protein Synthesis and Hypertrophy (mTOR) blog, hypertrophy occurs when muscles build proteins at a greater rate than they break them down. Adopting more scientific terms, we say that hypertrophy results from the rate of muscle protein synthesis (MPS) being higher than the rate of muscle protein breakdown (MPB).
By stimulating muscle protein synthesis and simultaneously inhibiting muscle protein breakdown, IGF-1 promotes gains in muscle mass.
On a related note, IGF-1 also activates specialized muscle cells called satellite cells. Satellite cells are a type of stem cell; they can transform into a variety of different muscle cells. In response to IGF-1, satellite cells fuse with muscle fibers and lay down new myofibrils: the thread like parts of muscle responsible for contraction. As you may recall from the Protein Synthesis and Hypertrophy (mTOR) blog, the creation of new myofibrils (called myofibrillar hypertrophy) leads to strength gains.
Given its role in muscle growth, people with higher circulating levels of IGF-1 may find it easier to build muscle and gain strength (as measured by a muscle’s maximal force output).
How does IGF-1 stimulate muscle protein synthesis?
IGF-1 exerts its effects in the body by binding to a particular receptor, the IGF-1 receptor (IGF-1R).
When IGF-1 binds to the IGF-1R, it triggers cascades of chemical reactions, which we term signalling pathways. One of the major signalling pathways activated by the IGF-1R is called the PI3K/AKT pathway. Incidentally, this pathway is also directly stimulated by exercise.
When activated by IGF-1R, the PI3K/AKT pathway stimulates molecules that switch-on the production of proteins. One of these molecules is mTOR, which we explored in the Protein Synthesis and Hypertrophy (mTOR) blog.
As well as promoting the production of new proteins, the PI3/AKT pathway also inhibits molecules (e.g. FoxO-1) that are responsible for the breakdown (or catabolism) of proteins.
- IGF-1 stimulates muscle growth by enhancing the building of new muscle proteins.
- IGF-1 also inhibits the breakdown of muscle protein.
- IGF-1 works by binding to IGF-1 receptors that trigger complex signalling pathways leading to the production of muscle proteins.
IGF-1 and ageing
IGF-1 is thought to play a role in cell division and cell death, both of which are a central part of the ageing process.
In studies of animals, it’s been widely shown that lower circulating levels of IGF-1 are linked to reduced ageing and a longer lifespan (longevity).
The picture in humans, however, is a bit more complicated, with research findings being mixed. Some studies of healthy centenarians (i.e. people who are 100 years old and over) suggest that they do indeed have relatively lower circulating levels of IGF-1.
Furthermore, fasting and caloric restriction (i.e. reducing the amount of calories you eat), which have been shown to delay cell ageing and improve lifespan, may also reduce circulating levels of IGF-1 in humans.
Both these lines of evidence suggest that lower circulating levels of IGF-1 are linked to reduced aging. Conversely, higher circulating levels of IGF-1 are associated with enhanced ageing.
One possible explanation for this link is that low IGF-1 levels causes better sensitivity to insulin (explained in the following section). Poor insulin sensitivity can, in turn, lead to inflammation and damage to cells, all of which speed up ageing.
When we consider that high IGF-1 levels also stimulate muscle growth, we can think of ageing as a potential downside to enhanced muscle growth. As you may have found out with your mTOR trait, this trade-off was also true of having increased mTOR activity.
- IGF-1 can promote ageing by stimulating cell growth, division and cell death.
- Low circulating IGF-1 levels have been linked to greater longevity.
- Increased ageing may be a downside to enhanced muscle growth.
IGF-1 and insulin sensitivity
IGF-1 (insulin-like growth factor 1) is so-called because it is similar in molecular structure to insulin: the hormone that allows tissues to take up and use sugar (glucose) from the bloodstream.
When our tissues are less responsive or sensitive to insulin, glucose levels in the blood start to rise. If blood glucose levels stay elevated over long periods, this causes inflammation and damage to cells and organs.
Studies suggest that IGF-1 can enhance our tissues’ sensitivity to insulin.
Both IGF-1 and insulin can bind to a special “hybrid” receptor called the IGF-1/insulin hybrid receptor. When this hybrid receptor is activated, it stimulates tissues (particularly skeletal muscle) to take up glucose from the blood stream.
Despite this effect, the relationship between circulating levels of IGF-1 and insulin sensitivity remains quite complicated. This is partly because IGF-1 can also suppress the release of growth hormone, which itself influences insulin function. According to clinical studies, both low and high levels of IGF-1 can lead to poorer insulin sensitivity.
- IGF-1 can influence our body's sensitivity to insulin and thereby affect our fat and glucose metabolism.
- Both excessively high and low circulating IGF-1 levels are linked to poor insulin sensitivity.
Your latest trait looks at variants of your IGF1 gene (which encodes the IGF-1 hormone) and your IGFBP3 gene (which encodes the IGFBP3 protein).
Variants of these genes affect your levels of circulating IGF-1. In turn, this influences your propensity for muscle growth and ageing, as well as your insulin sensitivity.
Be sure to check out your Insights and Actions to see what dietary, supplement, workout and lifestyle changes you can make to optimize your IGF-1 levels.
- FitnessGenes analyze variants of your IGF1 and IGBP3 genes.
- These gene variants affect circulating levels of IGF1.