Effects of adult onset mild calorie restriction on weight of reproductive organs, plasma parameters and gene expression in male mice.

Calorie restriction (CR) extends lifespan and delays onset of age-related diseases in various organisms, even when started later in life. Despite benefits for health and lifespan, CR's negative impact on reproduction is documented in some animals. Studies employing approximately 40% CR detected a delay in sexual maturation and impairment of fertility, which were combined with extension of the reproductive period. In contrast, mild CR (10-20%) is apparently not deleterious to reproduction. Hence, we hypothesized that mild CR started at 8 months of age would prolong reproductive capabilities and improve health parameters of male mice. To test this hypothesis, we assessed the effects of 10 and 20% CR on reproductive organ weights, selected plasma parameters and hepatic/testicular gene expression in normal male mice of heterogeneous genetic background. Starting at 8 months of age (adult), mice were assigned to 3 regimen groups: 10% CR (n = 8), 20% CR (n = 9) or ad libitum (AL; n = 8). Four months of CR were sufficient to reduce glycemia in a non-fasted protocol. Mild CR initiated in adulthood did not significantly impact final body weight, most of the analyzed plasma parameters or weight of androgen-dependent organs. Moreover, CR did not interfere with expression of the assessed testicular genes, or most of the hepatic genes, but it did cause an increase in the levels of peroxisome proliferator-activated receptor gamma (Pparg) and mouse sulfotransferase (mSTa); and a decrease in glucose-6-phosphatase-α (G6pc) mRNA, which might signify improvement of body condition. The important finding of our study was that a mild CR regimen, as low as 10 and 20%, was sufficient to impair glycemia in a non-fasted state, and also the levels of plasma IGF-1, corroborating the concept that mild CR has the potential for improving health and longevity, even when started later in life.

Effects of adult onset mild calorie restriction on weight of reproductive organs, plasma parameters and gene expression in male mice

Calorie restriction (CR) extends lifespan and delays onset of age - related diseases in vari ous organisms, even when started later in life. Despite benefits for health and lifespan, CR’s negative impact on reproduct ion is documented in some animals. Studies employing approximately 40% CR detected a delay in sexual maturation and impairment of fertility, which were combined with extension of the reproductive period. In contrast, mild CR (10 - 20%) is apparently not dele terious to reproduction. Hence, we hypothesized that mild CR started at 8 months of age would prolong reproductive capabilities and improve health parameters of male mice. To test this hypothesis, we assessed the effects of 10 and 20% CR on reproductive or gan weights, selected plasma parameters and hepatic/testicular gene expression in normal male mice of heterogeneous genetic background. Starting at 8 months of age (adult), mice were assigned to 3 regimen groups: 10% CR (n = 8), 20% CR (n = 9) or ad libitu m (AL ; n = 8). Four months of CR were sufficient to reduce glycemia in a non - fasted protocol. Mild CR initiated in adulthood did not significantly impact final body weight, most of the analyze d plasma parameters or weight of androgen - dependent organs. More over, CR did not interfere with expression of the assessed testicular genes, or most of the hepatic genes, but it did cause an increas e in the levels of peroxisome proliferator - activated receptor gamma ( Pparg ) and mouse sulfo transferase ( mSTa ); and a decre ase in glucose - 6 - phosphatase - α ( G6pc ) mRNA, which might signify improvement of body condition. The important finding of our study was that a mild CR regimen, as low as 10 and 20%, was sufficient to impair glycemia in a non - fasted state, and also the levels of plasma IGF - 1 , corroborating the concept that mild CR has the potential for improv ing health and longevity, even when started later in life.

Effects of adult onset mild calorie restriction on weight of reproductive organs, plasma parameters and gene expression in male mice

Calorie restriction (CR) extends lifespan and delays onset of age - related diseases in vari ous organisms, even when started later in life. Despite benefits for health and lifespan, CRs negative impact on reproduct ion is documented in some animals. Studies employing approximately 40% CR detected a delay in sexual maturation and impairment of fertility, which were combined with extension of the reproductive period. In contrast, mild CR (10 - 20%) is apparently not dele terious to reproduction. Hence, we hypothesized that mild CR started at 8 months of age would prolong reproductive capabilities and improve health parameters of male mice. To test this hypothesis, we assessed the effects of 10 and 20% CR on reproductive or gan weights, selected plasma parameters and hepatic/testicular gene expression in normal male mice of heterogeneous genetic background. Starting at 8 months of age (adult), mice were assigned to 3 regimen groups: 10% CR (n = 8), 20% CR (n = 9) or ad libitu m (AL ; n = 8). Four months of CR were sufficient to reduce glycemia in a non - fasted protocol. Mild CR initiated in adulthood did not significantly impact final body weight, most of the analyze d plasma parameters or weight of androgen - dependent organs. More over, CR did not interfere with expression of the assessed testicular genes, or most of the hepatic genes, but it did cause an increas e in the levels of peroxisome proliferator - activated receptor gamma ( Pparg ) and mouse sulfo transferase ( mSTa ); and a decre ase in glucose - 6 - phosphatase - α ( G6pc ) mRNA, which might signify improvement of body condition. The important finding of our study was that a mild CR regimen, as low as 10 and 20%, was sufficient to impair glycemia in a non - fasted state, and also the levels of plasma IGF - 1 , corroborating the concept that mild CR has the potential for improv ing health and longevity, even when started later in life.(AU)

Prolonged exposure to GH impairs insulin signaling in the heart.

Acromegaly is associated with cardiac hypertrophy, which is believed to be a direct consequence of chronically elevated GH and IGF1. Given that insulin is important for cardiac growth and function, and considering that GH excess induces hyperinsulinemia, insulin resistance, and cardiac alterations, it is of interest to study insulin sensitivity in this tissue under chronic conditions of elevated GH. Transgenic mice overexpressing GH present cardiomegaly and perivascular and interstitial fibrosis in the heart. Mice received an insulin injection, the heart was removed after 2  min, and immunoblotting assays of tissue extracts were performed to evaluate the activation and abundance of insulin-signaling mediators. Insulin-induced tyrosine phosphorylation of the insulin receptor (IR) was conserved in transgenic mice, but the phosphorylation of IR substrate 1 (IRS1), its association with the regulatory subunit of the phosphatidylinositol 3-kinase (PI3K), and the phosphorylation of AKT were decreased. In addition, total content of the glucose transporter GLUT4 was reduced in transgenic mice. Insulin failed to induce the phosphorylation of the mammalian target of rapamycin (mTOR). However, transgenic mice displayed increased basal activation of the IR/IRS1/PI3K/AKT/mTOR and p38 signaling pathways along with higher serine phosphorylation of IRS1, which is recognized as an inhibitory modification. We conclude that GH-overexpressing mice exhibit basal activation of insulin signaling but decreased sensitivity to acute insulin stimulation at several signaling steps downstream of the IR in the heart. These alterations may be associated with the cardiac pathology observed in these animals.