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Abstract
BackgroundGH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats.MethodsThree experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method.ResultsCompared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations.ConclusionsWe demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.
Highlights
IntroductionAge-related changes appear to be associated to decreases in these anabolic hormones
GH and IGFs serum levels decline with age
Effect of IGF-II therapy on anabolic hormones and serum total antioxidant status Consistent with previous studies [4], old animals showed a reduction in IGF-I and testosterone levels and a statistically significant increase of insulin levels
Summary
Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. We have previously studied some conditions of “IGF-I deficiency”, such as liver cirrhosis and aging, in which replacement therapy could be considered as an effective therapeutic strategy [4,5,6,7,8,9,10,11,12,13,14,15,16]. Age-related changes appear to be linked to decreases in these anabolic hormones. A significant amount of evidence has been accumulated showing that IGF-I might play a role in several pathological conditions usually observed during aging associated with oxidative damage [3,19,20,21]
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