leptin and Cataract

Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (+/-0.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

Topics: Algorithms; Animals; Artificial Intelligence; Body Weight; Cataract; Female; Genetic Heterogeneity; Insulin-Like Growth Factor I; Leptin; Life Expectancy; Longevity; Male; Mice; Mice, Inbred Strains; Models, Statistical; T-Lymphocyte Subsets; Thyroxine

We have previously demonstrated that two wild-derived stocks of mice, Idaho and Majuro, are significantly longer-lived than mice of a control stock (DC) generated as a four-way cross of commonly used laboratory strains of mice. This study provides independent confirmation of this earlier finding, as well as examining serum glucose, insulin, leptin, glycated hemoglobin (GHb), cataract severity, and glucose tolerance levels in each of the stocks. Both the mean (+20%) and maximum (+13%) life span of the Idaho mice were significantly increased relative to the DC stock, while in the Majuro mice only maximum (+15%) life span was significantly increased. In addition, Majuro mice were hyperglycemic in both the fed and fasted states compared both to laboratory-derived and Idaho stocks, had significantly elevated GHb levels and cataract scores, and were glucose intolerant although serum insulin levels did not differ between stocks. Body weight and body mass index (BMI)-corrected leptin levels were also dramatically (1.5-3-fold) higher in the Majuro mice. The longevity of Id mice was not accompanied by changes in serum glucose and insulin levels, or glucose tolerance compared to DC controls, although GHb levels were significantly lower in the Idaho mice. Taken together, these findings suggest that neither a reduction of blood glucose levels nor an increase in glucose tolerance is necessary for life span extension in mice.

Topics: Animals; Blood Glucose; Body Mass Index; Cataract; Female; Glucose Tolerance Test; Glycated Hemoglobin; Growth; Hyperglycemia; Insulin; Leptin; Longevity; Mice; Mice, Inbred Strains; Survival Analysis

Topics: Aging; Cataract; Female; Humans; Leptin; Obesity

The improved prognosis and increased expected lifetime among long-term survivors of childhood malignancies have made these patients especially sensitiveto the late toxicity of cancer therapy and prone to secondary malignancies. Recently, new strategies aiming to protect against cancer treatment toxicity have been developed, including the drug amifostine (Ethyol), which is suggested to protect normal tissues from the toxic effects of radiation and cytotoxic agents. In the present study, the possible protective effect of amifostine against toxicity induced by a single injection of doxorubicin (3 mg/kg) in immature rats was evaluated. Specifically, we evaluated the protection against long-term toxicity and the effects of amifostine on growing immature tissues. Amifostine (50-200 mg/kg) given 15 min before doxorubicin had a significant protective effect against doxorubicin-induced early alopecia in young rats. Significant protection against cataract formation was obtained by the use of low-dose amifostine (50 mg/kg). However, amifostine did not protect young rats against the late toxic effect of doxoubicin on linear growth, body weight, plasma leptin levels, and heart or testicular tissue. Worrisome, and in contrast to earlier studies in adult rats, an increased doxorubicin toxicity actually was observed and mortality was increased when the higher doses of amifostine (100-200 mg/kg) were used. The present results suggest that more data from growing immature animal models are needed to analyze the safety of amifostine treatment and its mechanisms of action before wider clinical use of this drug in pediatric cancer patients is recommended.

Topics: Age Factors; Alopecia; Amifostine; Animals; Animals, Suckling; Antibiotics, Antineoplastic; Body Weight; Cardiomyopathies; Cataract; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart; Leptin; Male; Myocardium; Rats; Rats, Sprague-Dawley; Testicular Diseases; Testis; Testosterone