Trade off between Growth Hormone & IGF-1 vs Longevity

[MiamiNice]

I have read that there is a trade off when it comes to growth hormone and IGF-1 & Longevity . Growth hormone and IGF-1 enhance muscle and cognitive performance but this comes at a cost: longevity. Reduced growth hormone and IGF-1 increase lifespan by increasing the expression of genes involved in stress resistance but at an expensive cost when it comes to muscles and brain.    What good is it to live longer if the price is muscular frailty & decreased cognition?  How do CR members arrive at a compromise.

[Michael R]

The super-short version is that the way you've phrased the dilemma is somewhat oversimplified. IGF-1 boosts brain and muscle in the short term, but in the long term most-but-not-all animal studies and studies of people with genetic IGF-1 signaling deficits suggest that it actually accelerates their decline. There's also the issue that IGF-1 levels tend to decline late in life due to the aging process itself, whereas they stay steady but low on CR or in IGF-1 mutant mice, and these are quite different physiological states. There may be an advantage to boosting them up in people whose IGF-1 levels have declined as a result of aging (I mean people in their last decades, not middle-aged people), though clinical trials have not largely supported the idea, but that's quite different from sustaining high levels thru' the rest of one's life. See for instance here and here.

[Jonnywallter]

So, fasting, for example intermittent fasting or warrior diet, suppose to extend your lifespan and increase lean body mass due to higher release of growth hormone, but you are saying that increased growth hormone decreases lifespan and muscle mass drill. I am confused. Could someone explain, please?

[Saul]

On 8/18/2018 at 8:48 AM, Michael R said:

 

Hi Johnny!

No; the evidence is that CR (or probably IF) REDUCES serum IGF1, and therefore might possibly result in extended healthspan and maximal LS.  

The simple summary:  Supplementing GH, or eating excessive animal protein, will increase serum IGF1, and is great for increasing muscle mass;   but it's terrible if you want to lead a long and healthy life.

--  Saul  

[mccoy]

By the way, skeletal muscle mass can be of course boosted by stymulation of mTOR thru the mechanoreceptors. The IGF-1→PI3K→akt signal may be (at least in part) replaced by the Load/stress→PI3K→akt signal.

The above in theory and I'm just exploring the possibilities. A  very low IGF-1 signal will tend to prevent muscle growth anyway, on the other side it's probably all right to have a moderate IGF-1 signal if an appropriate loading stress is regularly applied to the muscle tissues.

Right now I believe I'm in this category: moderate IGF-1 signal but regular loading and metabolic stress signal. The result is not as conspicuos as High IGF-1 + Hi loading, but it comes with some advantages, such as slow increase of lean mass without concomitant  significant increase of adipose tissue together with the fast increase in muscle mass.  My personal limitation si also that I cannot apply elevated levels of mechanical loading .

According to the bodybuilders themselves, lowering the IGF-1 signal by a keto diet will inhibit mTOR in muscles even in presence of the mechanical stymulus. In fact, bodybuilders will use a keto diet for pre-contest definition, accepting some muscle shrinkage coupled to loss of most adipose tissue.

[Todd Allen]

The following two studies suggest a U shaped curve when graphing mortality with respect to IGF-1 with values in the 50th to 60th population percentile probably ideal. 

Both Low and High Serum IGF-I Levels Associate with Cancer Mortality in Older Men

Conclusions:
Our findings demonstrate that both low and high serum IGF-I levels are risk markers for increased cancer mortality in older men. Moreover, low IGF-I levels associate with increased CVD mortality.

Meta-Analysis and Dose-Response Metaregression: Circulating Insulin-Like Growth Factor I (IGF-I) and Mortality

In conclusion, our findings suggest that IGF-I and IGFBP-3 are associated with mortality. Both low and high IGF-I increased all-cause, CVD, and cancer mortality, whereas only low IGFBP-3 is associated with mortality. Our data are suggestive of optimal IGF-I levels between 0 and 1 SD in adult patients.

 

But  these don't address whether a steady state or cycling up and down are better.  My guess is that chronically low or high leads to trouble despite there being beneficial effects at both extremes.  Myself with a genetic neuro-muscular wasting disease, SBMA, with very broadly dysregulated nuclear transcription, mostly down regulated, due to poor clearance of a mutant protein, I've been having good results cycling  between  phases using dietary restriction in combination with supplements targeted at maximizing catabolism/autophagy followed by phases of dietary excess (especially higher animal sourced proteins) and supplements maximizing anabolism via mTOR, IGF-1, etc.  Trying to find my optimal pattern is a work in progress.   I've been roughly basing the timing of each phase on blood sugar levels, ending catabolic phases when my blood sugar is averaging below 75 mg/dl and anabolic phases when I'm averaging over 100 mg/dl.   As  my body fat % has declined the ratio of anabolism to catabolism time is increasing.