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Rapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin Synthesis in Aged Rats
This investigation examines whether a low intermittent dose of rapamycin will avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin while still decreasing body weight and adiposity in aged obese rats. Furthermore, we examined if the rapamycin-mediated decrease in serum leptin was a reflection of decreased adiposity, diminished leptin synthesis, or both. To these ends, rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old rats. Body weight, food intake, body composition, mTORC1 signaling, markers of metabolism, as well as serum leptin levels and leptin synthesis in adipose tiss...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Scarpace, P. J., Matheny, M., Strehler, K. Y. E., Toklu, H. Z., Kirichenko, N., Carter, C. S., Morgan, D., Tümer, N. Tags: Original Article Source Type: research

Sex-specific Tradeoffs With Growth and Fitness Following Life-span Extension by Rapamycin in an Outcrossing Nematode, Caenorhabditis remanei
Rapamycin inhibits the nutrient-sensing TOR pathway and extends life span in a wide range of organisms. Although life-span extension usually differs between the sexes, the reason for this is poorly understood. Because TOR influences growth, rapamycin likely affects life-history traits such as growth and reproduction. Sexes have different life-history strategies, and theory predicts that they will resolve the tradeoffs between growth, reproduction, and life span differently. Specifically, in taxa with female-biased sexual size dimorphism, reduced growth may have smaller effects on male fitness. We investigated the effects o...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Lind, M. I., Zwoinska, M. K., Meurling, S., Carlsson, H., Maklakov, A. A. Tags: Original Article Source Type: research

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen—2mg/kg administered every 5 days—with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Arriola Apelo, S. I., Pumper, C. P., Baar, E. L., Cummings, N. E., Lamming, D. W. Tags: Brief Report Source Type: research

Rapamycin Versus Intermittent Feeding: Dissociable Effects on Physiological and Behavioral Outcomes When Initiated Early and Late in Life
Rapamycin, an inhibitor of the mammalian target of rapamycin pathway, has been shown to increase mammalian life span; less is known concerning its effect on healthspan. The primary aim of this study was to examine rapamycin’s role in the alteration of several physiological and behavioral outcomes compared with the healthspan-inducing effects of intermittent feeding (IF), another life-span-enhancing intervention. Male Fisher 344 x Brown Norway rats (6 and 25 months of age) were treated with rapamycin or IF for 5 weeks. IF and rapamycin reduced food consumption and body weight. Rapamycin increased relative lean mass an...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Carter, C. S., Khamiss, D., Matheny, M., Toklu, H. Z., Kirichenko, N., Strehler, K. Y. E., Tümer, N., Scarpace, P. J., Morgan, D. Tags: Original Article Source Type: research

Rapamycin Attenuates Age-associated Changes in Tibialis Anterior Tendon Viscoelastic Properties
Rapamycin extends mouse life span, but the extent to which rapamycin prevents aging-associated changes in specific tissues remains unclear. Stiffness increases and collagen turnover decreases in mouse tendon with aging; thus, our aim was to determine the effect of long-term rapamycin treatment on the mechanical and structural properties of tendons from old mice. Tendons were harvested from female UM-HET3 mice maintained on a standard chow diet for 4 (adult) or 22 (old) months or fed chow containing polymer-encapsulated rapamycin (eRAPA) from 9 to 22 months of age (old RAPA). Stiffness was twofold higher for tendons of old ...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Zaseck, L. W., Miller, R. A., Brooks, S. V. Tags: Original Article Source Type: research

Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes
We examined the effect of rapamycin on the life span of a mouse model of type 2 diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-lepr db/db mice (db/db) were placed on either a control diet, lacking rapamycin or a diet containing rapamycin and maintained on these diets over their life span. Rapamycin was found to reduce the life span of the db/db mice. The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender dif...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Sataranatarajan, K., Ikeno, Y., Bokov, A., Feliers, D., Yalamanchili, H., Lee, H. J., Mariappan, M. M., Tabatabai-Mir, H., Diaz, V., Prasad, S., Javors, M. A., Ghosh Choudhury, G., Hubbard, G. B., Barnes, J. L., Richardson, A., Kasinath, B. S. Tags: Original Article Source Type: research

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of ...
Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - June 13, 2016 Category: Geriatrics Authors: Arriola Apelo, S. I., Lamming, D. W. Tags: Review Source Type: research

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Source: Journals of Gerontology Series A: Biological Sciences and Medical Sciences - May 11, 2016 Category: Geriatrics Tags: Erratum Source Type: research