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IGF-1 Protects Mitochondria
E-Newsletter No. 77
Serum levels of insulin-like growth factor 1 (IGF-1) decrease with age. Recently
Inma Castilla-Cortazar, M.D. at the University USP-CEU in Madrid, Spain,
and her research team reported that exogenous administration of hGH to aging
rats restored circulating IGF-1 levels and reversed some age-related
changes. They suggested that aging could be an unrecognized deficiency in IFG-1.
Subsequent research has revealed that mitochondria regulate apoptosis and mitochondrial membrane damage can allow apoptotic effectors to leak, causing cell death. Because mitochondria are one of IGF-1's most important cellular targets, Dr. Castilla-Cortazar's team theorized that IGF-1 acts by reducing mitochondrial damage in aging cells, protecting them from apoptosis.
The researchers examined mitochondrial function in old and young (control) rats. The older animals showed higher oxidative damage in isolated mitochondria, depleted membrane potential, increased proton leak rates, elevated intra-mitochondrial free radical production, and significant reduction of ATPase and complex IV activities. Their mitochondrial respiration was actractyloside insensitive, suggesting that the adenine nucleotide translocator (ANT)
-- one of the most vulnerable locations for pore opening in mitochondrial membranes -- was uncoupled. The older animals had significantly increased expression of the active fragments of caspase 3 and 9.
hGH induced therapy reduced the exidative mitochondrial damage in old rats and also reduced caspase activation. IGF-1 increased ATP production, which could cause the beneficial metabolic effects of IGF-1.
In their paper, to be published soon in Endocrinology*, the researchers conclude that IGF-1 reduced cell death from oxidative stress by protecting the aging cells against mitochondrial damage, which increased ATP production and reduced free radical production, oxidative damage, and apoptosis.
* Puche J.F., Castilla-Cortazar M., Montaine J, et al. Low doses of insulin-like growth factor induce mitochondrial protection in aging rats. Endocrinology, in
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