Lexicon
IGF-1
Also known as Insulin-like growth factor 1
Definition
Insulin-like growth factor 1 (IGF-1) is a key growth factor that regulates both anabolic and catabolic pathways in skeletal muscle. [1] IGF-1 is produced under the drive of growth hormone, and persistent excess of both growth hormone and IGF-1 produces the multi-system disease acromegaly. [2] [3] Insulin/IGF-1 signaling is one of the key genetic pathways that regulate lifespan and healthspan, alongside sirtuins, AMP-activated protein kinase, and the target of rapamycin. [4]
How it works
IGF-1 increases skeletal muscle protein synthesis via the PI3K/Akt/mTOR pathway and inhibits protein degradation by suppressing FoxO-driven E3 ubiquitin ligases and the ubiquitin-proteasome system. [1] An age-related decrease in the production of anabolic hormones such as testosterone, growth hormone, and IGF-1 impairs the capacity of skeletal muscle to incorporate amino acids and synthesize proteins. [5] Together with the target of rapamycin pathway, insulin/IGF-1 signaling underlies the central role of mitochondria in the aging process. [6] Hormones such as growth hormone and IGF-1 have been shown to increase muscle mass in patients suffering from diseases related to muscle atrophy, reflecting the anabolic role of IGF-1 in skeletal muscle [7]
Connected concepts
How it's measured
Because endogenous growth hormone secretion is episodic and pulsatile, random measurement of serum growth hormone is not recommended to screen for growth hormone disorders, whereas IGF-1 provides a more stable integrated marker of growth hormone action. [8] Interpretation of IGF-1 is complicated by heterogeneity between assays as well as individual patient factors and differences in age-specific cut-offs. [8]
What levels mean
In suspected acromegaly, serum IGF-1 measurement is the recommended initial screening test, with the oral glucose tolerance test and concomitant growth hormone measurement remaining the gold-standard confirmatory test. [9] In acromegaly, normalization of IGF-1 and growth hormone are the primary therapeutic aims, and IGF-1 and growth hormone should be considered together because various conditions can alter their levels. [2] [10]
Community knowledge
## Klotho And Gene-Therapy Mechanisms
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- 1.Yoshida T, Delafontaine P. Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy. Cells · 2020
- 2.Fleseriu M, Langlois F, Lim DST, Varlamov EV, Melmed S. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol · 2022
- 3.Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am · 2008
- 4.North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res · 2012
- 5.Deschenes MR. Effects of aging on muscle fibre type and size. Sports Med · 2004
- 6.Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest · 2013
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