Just as an aside…
The company Loyal for Dogs is coming out with a new IGF-1 inhibition drug to extend life in dogs (and eventually humans). But there is already an IGF-1 inhibition drug approved for people.
I came across this paper:
see this section:
Inhibitors of the GH/IGF-1 axis
Although the lack of global IGF-1 signaling is lethal, data from studies conducted in animal models have shown that a reduction in IGF-1 levels or IGF-1 action can extend lifespan. Additionally, human IGF-1 receptor gene polymorphisms are associated with exceptional longevity (Suh et al., 2008), and recently, Barzilai and colleagues have shown that low plasma IGF-1 concentrations predict survival in long-lived people (Milman et al., 2014), specifically in women with a history of cancer. In animals, dwarf, long-lived mice lacking the growth hormone receptor (GHR-/-) have reduced levels of IGF-1, are insulin sensitive despite obesity, and have decreased risk for cancer and diabetes (Zhou et al., 1997; Shevah & Laron, 2007; Ikeno et al., 2009). Importantly, similar results have been reported in growth hormone receptor-deficient Laron syndrome (LS) patients. In this regard, no formal aging studies have been performed on patients with LS; however, they are protected from diabetes and fatal neoplasms. (Guevara-Aguirre et al., 2011; Steuerman et al., 2011). Thus, pharmaceutical interventions that directly lower IGF-1 levels in adults could improve health and prolong lifespan.
Pharmacological targets for lowering IGF-1 action include those that act directly or indirectly on cells/tissues that produce or respond to GH and/or IGF-1. In this regard, human or humanized monoclonal antibodies and drugs directed against the IGF-1R have been used in clinical trials to treat several types of cancer (Warshamana-Greene et al., 2005; Carboni et al., 2009); however, none have been approved for clinical use. We are unaware of the development of any antibody against GH or IGF-1, but several classes of compounds that inhibit the GH/IGF-1 axis have been approved for use in patients with acromegaly. Recently, a consensus document has been developed for the use of this therapeutics (Giustina et al., 2014). One of these drug classes, somatostatin analogues, lower serum GH levels by suppressing GH secretion by pituitary somatotrophs, thereby ultimately decreasing serum IGF-1 levels. Unfortunately, these compounds also suppress secretion of other endocrine hormones, including insulin. Furthermore, only 20-50% of patients with acromegaly respond to these drugs, and significant adverse events have been documented including gallstones, diarrhea, and anorexia. Thus, the use of somatostatin analogues to increase longevity or healthspan appears to be unwarranted at this time.
The second approved drug for treating acromegaly is the GH receptor antagonist pegvisomant (Trainer et al., 2000; van der Lely et al., 2001; Kopchick et al., 2002; van der Lely & Kopchick, 2006). Pegvisomant is unique in that it does not inhibit GH secretion, but rather inhibits GH action by binding to and blocking the GHR (Kopchick et al., 2002). Notably, a dose-dependent decrease of IGF-1 levels is seen in up to 90% of pegvisomant-treated patients (Trainer et al., 2000; van der Lely et al., 2001; Kopchick et al., 2002; van der Lely & Kopchick, 2006). Additionally, pegvisomant is an insulin sensitizer that blocks the diabetogenic action of GH and thus produces beneficial effects on glucose metabolism. Pegvisomant, therefore, could have positive effects on both longevity and healthy aging by lowering serum IGF-1 and increasing insulin sensitivity. Regarding adverse effects, van der Lely et al. (2012)reported that Long-term data on the efficacy and safety profile of pegvisomant are reassuring and few long-term serious adverse events have been reported but ongoing vigilance is required to monitor liver function and tumor size. Thus, pegvisomant is an approved drug that should be tested for its effects on longevity and healthy aging. Future therapeutics targeted at inhibiting the GH/IGF-1 axis could include small inhibitory RNAs directed against the GHR or IGF-1 receptor mRNAs, monoclonal antibodies directed against GH or IGF-1, or novel GHR or IGF-1R tyrosine kinase inhibitors.
Another way to reduce global IGF-1 action may be to inhibit IGF-1 availability. For example, loss of PAPP-A, a protease that cleaves and inactivates the IGF-1 sequestering protein IGFBP-4, reduces IGF-1-induced signaling without affecting overall serum IGF-1 levels and not only extends mouse lifespan, but has many other beneficial effects on healthspan and age-related diseases (Conover, 2012).
In summary, reducing the activity of the GH/IGF-I somatotrophic axis is perhaps the most validated and consistent genetic intervention to extend mouse lifespan and healthspan. In addition GHR/IGF-I deficiency is also among the few phenotypes that is well characterized in humans (patients with Laron syndrome) with very few side effects in adults, even considering the extreme level of GH receptor deficiency and the resulting >80% reduction in circulating IGF-I. Notably, a pharmaceutical intervention targeting this pathway may or may not be designed to achieve such a low level of hepatic IGF-I secretion
and this paper:
its extremely likely that this drug called somavert extends lifespan in mammals…
Injection site common side effect…
https://www.pfizermedicalinformation.com/en-us/node/62776/pi_section/field_spl_instructions
“Pegvisomant is unique in that it does not inhibit GH secretion, but rather inhibits GH action by binding to and blocking the GHR. pegvisomant is an insulin sensitizer that blocks the diabetogenic action of GH and thus produces beneficial effects on glucose metabolism. Pegvisomant, therefore, could have positive effects on both longevity and healthy aging by lowering serum IGF-1 and increasing insulin sensitivity”
