IGF-1, IGF1Ec or MGF, muslce hypertrophy

[mccoy]

I've started reading what is considered one of the main references for muscle hypertrophy:

 

 

One very interesting issue described is IGF-1 and its Isomorphs, I'm trying to summarize here.

• In humans have been identified 3 different isoforms of IGF-1: IGF-1Ea, IGF-1Eb, IGF-1Ec
• Ea and Eb are produced mainly in the liver and then released into the systemic circulation
• However, muscle contraction produces the majority of systemic IGF-1 during intense exercise and much of the circulating IGF-1 is taken up by active myofibers
• IGF-1Ec is also called mechano growth factor (MGF) since it si stimulated by mechanical load on muscles; its peptide sequence is different from the systemic isoform.
• MGF acts locally as opposed to systemically
• Sarcopenia is caused by the age-related decrease in serum IGF-1 and this suggests the existence of a threshold below which muscle mass is compromised.
• IGF-1 is a potent signal for the PI3K/Akt pathway which stymulates the mTOR pathway but it is not clear if it has a primary role in the anabolic response to exercise
• Serum concentrations of IGF-1 are not necessarily correlated with postworkout increases in muscle protein synthesis and IGF-1 impaired mice (only 20% of normal values) do not exhibit a compromised hypertrophic response to exercise.
• Systemic IGF-1 upregulation after exercise is delayed in coincidence with satellite cell regulation and this may be related to its ability to stimulate differentiation and fusion following myotrauma.

Obviously, the issue has a degree of complexity which is usually not discussed. There is systemic IGF-1 released by the liver, but also systemic IGF-1 upregulated by intense exercise, which is sequestered by muscle cells themselves so maybe the net effect on the system is not so significant. In addition, there is local IGF-1 in its isoform Ec or MGF which is released by exercise. 

 

[mccoy]

One aspect of the above reasoning is that too low a IGF-1 serum concentration, like in too rigid CR, may cause sarcopenia even before old age and this maybe (excessive frailty) is one of the factors which contributes to the increased mortality HR when IGF-1 serum levels are too low (usually below 100 micrograms/dL as I understand it but the threshold for muscle atrophy may be different). 

Edited November 23, 2019 by mccoy

[Ron Put]

Interesting observations, mccoy. Thanks!

I am a bit confused by the IGF-1 studies and what they mean for health and longevity.

Curious if others have sensible argument pro and con?

[Saul]

IMO, a simple summery: Keap protein consumption, especially animal protein, low, in order to keep IGF1, and other growth hormones, low -- as part of your effort to increase healthspan and (possibly} lifespan.  But do regular (most days a week) vigorous aerobic exercise -- preferably with some resistance -- to keep your muscles small, but healthy.

(Massive muscles consume a lot of calories -- they are not consistent with the goals of maximum lifespan or healthspan.)

  --  Saul

[mccoy]

2 hours ago, Saul said:

Massive muscles consume a lot of calories -- they are not consistent with the goals of maximum lifespan or healthspan

Massive muscles have some health benefits though, like increased glucose uptake and IGF-1 uptake as we've seen. True enough, to maintain more muscle mass higher intake of carbs and protein is needed, so at the end, the balance is even. But massive muscles also tend to protect from some injuries and to provide additional body functionality. If we don't get injured during workouts, of course.

I would conclude that probably it is not that they are not consistent with the goals of maximum lifespan or healthspan, rather than it is very very hard to exhibit muscle hypertrophy beyond a certain age, because of many reasons among which decline in androgen hormones, so they are not usually present when the higher percentiles of life expectancy are reached.

[mccoy]

4 hours ago, Ron Put said:

I am a bit confused by the IGF-1 studies and what they mean for health and longevity.

You are not the only one!

I remember that Valter Longo during his stemtalk podcast said that the reason why he suggests higher protein after 65 years is to counteract the decline in systemic IGF-1 and subsequent sarcopenia.

He also said that higher protein can be avoided if we lift weights every day. This is consistent with the release of MGF and systemic IGF-1, independent of protein and methionine ingestion.

 

[mccoy]

Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping

In the above brief article, there are a few interesting details on the MGF, which of course can be used as a therapeutic factor when muscle atrophy is a problem: sarcopenia, metabolic ailments, astronauts after prolonged low-gravity missions, recovery after immobilization.

[Saul]

I suggest ignoring Walter Longo.

  --  Saul