The IGF-1 Trade-Off: Performance vs. Longevity

running

credit:Chris Hunkeler

During the relatively recent fireside talk put together by WellnessFX Tim Ferriss brought up the point that in some cases there may exist a trade-off or a “faustian bargain” (as he called it) between longevity and performance. Watch the fireside talk here.

Optimizing for IGF-1, otherwise known as insulin-like growth factor-1, is one such case where more performance driven goals like maximizing growth and maintaining muscle and neurons may, to some degree, come at odds with ones desire for longevity.

The reason for this is that, aside from IGF-1’s more notorious role in building muscle, it has been shown to have some very interesting properties that haven’t entered mainstream dialogue as of yet: mice deprived of IGF-1 live longer. We’ll get back to that in a second, though.

Click here to view the video: http://youtu.be/AjSl4n_KdOY

First, let’s go over a few of the growth hormone and IGF-1 and basics.
Growth hormone and insulin-like growth factor-1 (IGF-1) are hormones that have complex roles in the aging process. The relationship between growth hormone and IGF-1 is this: growth hormone, secreted by the pituitary, stimulates the production of IGF-1 by acting on the liver where it is made.1 Because of this very close relationship between IGF-1 and growth hormone many people conflate the two.

The growth-promoting effects most people associate with growth hormone are actually mediated through IGF-1, which has characteristics of both hormone and growth factor since it stimulates the growth, proliferation, and survival of cells.1 There is also a negative feedback loop in place such that elevated levels of IGF-1 tune down the production of growth hormone.1 This negative feedback loop is important since IGF-1 enhances cellular survival of all cells including precancerous.2

There is an age-related decline in the levels of growth hormone and IGF-1. Growth hormone levels progress through the following general pattern throughout a persons life: they are almost undetectable at birth and then rapidly rise until puberty at which point they remain steady until about 50 years of age when they start to drop precipitously.3

Growth hormone and IGF-1 enhance muscle and cognitive performance
IGF-1 plays a very important role in both promoting and maintaining muscle mass and neuronal function. Things to know about IGF-1 and growth hormone:

  • IGF-1 released in response to growth hormone is anabolic: it promotes growth and repair of skeletal muscle. 4,5
  • Exercise can induce growth hormone release and thus IGF-1.
  • This process of growth hormone release in response to exercise is largely proportional to the strenuousness of the activity.6
  • A person can become acclimated to the strenuousness of the activity, and not release as much growth hormone over time.6
  • A 30-60 minute sauna session increases growth hormone by 140%.7
  • IGF-1 acts as a neurotrophic factor in the brain, contributing to neurogenesis (growth of new brain cells) and survival of existing neurons (neuroprotective).8
  • Exercised-induced neurogenesis is mediated through IGF-1 induced during exercise.8

The age-related decline in growth hormone and associated IGF-1 has been linked to age-related muscle atrophy, increased adipose tissue, and neuronal dysfunction.2,9 In fact, growth hormone replacement therapy in elderly men has been shown to increase lean body mass.9 Growth hormone therapy (1 mg/day—for 5 months) has also been used to improve cognitive function in healthy adults and adults with mild cognitive impairment.10 While only modest amounts of growth hormone cross the blood-brain barrier, IGF-1, which is actually responsible for the cognitive benefits, gets across just fine. The brain-boosting benefits of growth hormone therapy included better executive function and verbal memory.10 This is strong evidence suggesting that IGF-1 both enhances performance and prevent atrophy of skeletal muscle and the brain.

The trade-off: decreased growth hormone and IGF-1 increase longevity
Finding safe and effective ways to increase growth hormone and IGF-1 naturally, thereby, improving muscle and brain function while simultaneously preventing their atrophy seems like a no-brainer, who doesn’t want to be more fit and smarter—for longer? Or is it longer? Mice, worms, and flies that are genetically engineered to be deficient in either growth hormone or IGF-1 live almost 50% longer than controls, which is a huge increase in lifespan.2,11The converse has also shown to be also true: Overexpressing growth hormone by 100 to 1,000-fold in mice causes a 50% shorter lifespan, mainly due to kidney and liver dysfunction.12 The same results have been demonstrated in lower invertebrate species such as worms and flies, suggesting that this mechanism is evolutionarily conserved.13,14 Okay, admission here: either eliminating growth hormone or blasting it 1000-fold in mice is rather extreme.

IGF-1 polymorphism linked to centenarian lifespan
If you’re not quite convinced that the aging component to all of this is something that might also be relevant to humans consider this: polymorphisms (variations) in the gene that encodes for the IGF-1 receptor, which leads to decreased IGF-1 levels, have been associated with the longer lifespan found in centenarians.15,16

The longevity mechanism
So what is the mechanism? Why does decreasing growth hormone and IGF-1 signaling increase lifespan when it has such an important role in muscle and brain function? It is thought that curtailing IGF-1 levels increase the expression of other genes that are involved in stress resistance, particularly oxidative damage.2 Oxidative damage, which is generated everyday through a variety of ways including UV radiation and normal metabolism, puts wear and tear on every tissue in our body and on our DNA. If we can boost the activity of anti-oxidant genes that help stave off this damage, then we should be able to delay the deterioration of our tissues and our DNA, thus extending longevity.

While you will increase your lifespan by lowering your growth hormone and IGF-1 levels, you will experience downsides to having low levels of IGF-1, namely:

  • Stunted growth11
  • Decreased fecundity and sterility17
  • Muscle atrophy9
  • Brain dysfunction10
  • Diminished sex dive2

All of these things will sure make you FEEL like you are living longer, which in this case is a bad thing because you actually DO live longer!

Hormesis: an alternative longevity mechanism
There are some other lifestyle factors that can also boost the expression of stress resistant genes without the downsides to low levels of growth hormone and IGF-1. This is called hormesis, a low dose to something that would otherwise be harmful will increase the expression of genes that deal with stress. The “hermetic effect” is actually the mechanism of action of many catechins and polyphenols that are often mislabeled as antioxidants.

Catechins and polyphenols are found in:

  • Green tea
  • Blueberries and other purple-pigmented fruits/vegetables
  • Dark chocolate
  • Wine
  • Turmeric

Catechins and polyphenols on their own have no ability to “scavenge“ free radicals like classic anti-oxidants such as vitamins C and E. Rather, they are a little toxic to our cells and thus induce a “hormetic response” by increasing the expression of anti-oxidant genes, and this is why the are anti-oxidants.

There you have it. It’s a trade-off when it comes to growth hormone and IGF-1. More of it enhances muscle and neuronal growth while simultaneously preventing atrophy. Less of it will increase the expression of stress resistance genes and extend your lifespan. Which do you prefer, having better muscle and cognitive performance or living longer?

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References

  1. Annunziata, M., Granata, R. & Ghigo, E. The IGF system. Acta diabetologica 48, 1-9, doi:10.1007/s00592-010-0227-z (2011).
  2. Sonntag, W. E., Csiszar, A., deCabo, R., Ferrucci, L. & Ungvari, Z. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies. The journals of gerontology. Series A, Biological sciences and medical sciences 67, 587-598, doi:10.1093/gerona/gls115 (2012).
  3. Corpas, E., Harman, S. M. & Blackman, M. R. Human growth hormone and human aging. Endocrine reviews 14, 20-39 (1993).
  4. Velloso, C. P. Regulation of muscle mass by growth hormone and IGF-I. British journal of pharmacology 154, 557-568, doi:10.1038/bjp.2008.153 (2008).
  5. Mourkioti, F. & Rosenthal, N. IGF-1, inflammation and stem cells: interactions during muscle regeneration. Trends in immunology 26, 535-542, doi:10.1016/j.it.2005.08.002 (2005).
  6. Gatti, R., De Palo, E. F., Antonelli, G. & Spinella, P. IGF-I/IGFBP system: metabolism outline and physical exercise. Journal of endocrinological investigation 35, 699-707, doi:10.3275/8456 (2012).
  7. Lammintausta, R., Syvalahti, E. & Pekkarinen, A. Change in hormones reflecting sympathetic activity in the Finnish sauna. Annals of clinical research 8, 266-271 (1976).
  8. Llorens-Martin, M., Torres-Aleman, I. & Trejo, J. L. Mechanisms mediating brain plasticity: IGF1 and adult hippocampal neurogenesis. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 15, 134-148, doi:10.1177/1073858408331371 (2009).
  9. Rudman, D. et al. Effects of human growth hormone in men over 60 years old. The New England journal of medicine 323, 1-6, doi:10.1056/NEJM199007053230101 (1990).
  10. Baker, L. D. et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Archives of neurology 69, 1420-1429, doi:10.1001/archneurol.2012.1970 (2012).
  11. Brown-Borg, H. M., Borg, K. E., Meliska, C. J. & Bartke, A. Dwarf mice and the ageing process. Nature 384, 33, doi:10.1038/384033a0 (1996).
  12. Bartke, A., Chandrashekar, V., Bailey, B., Zaczek, D. & Turyn, D. Consequences of growth hormone (GH) overexpression and GH resistance. Neuropeptides 36, 201-208 (2002).
  13. Kenyon, C., Chang, J., Gensch, E., Rudner, A. & Tabtiang, R. A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464, doi:10.1038/366461a0 (1993).
  14. Broughton, S. J. et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proceedings of the National Academy of Sciences of the United States of America 102, 3105-3110, doi:10.1073/pnas.0405775102 (2005).
  15. Bonafe, M. et al. Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. The Journal of clinical endocrinology and metabolism 88, 3299-3304 (2003).
  16. Suh, Y. et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proceedings of the National Academy of Sciences of the United States of America 105, 3438-3442, doi:10.1073/pnas.0705467105 (2008).
  17. Bartke, A. Growth hormone and aging: a challenging controversy. Clinical interventions in aging 3, 659-665 (2008).

The posts on this blog are for information only, and are not intended to substitute for a doctor-patient or other healthcare professional-patient relationship nor do they constitute medical or healthcare advice of any kind. Any information in these posts should not be acted upon without consideration of primary source material and professional input from one's own healthcare professionals.