Sirolimus

Publication Title: 
Aging Cell

Significant extension of lifespan in important mammalian species is bound to attract the attention not only of the aging research community, but also the media and the wider public. Two recent papers published by Harrison et al. (2009) in Nature and by Colman et al. (2009) in Science report increased longevity of mice fed with rapamycin and of rhesus monkeys undergoing caloric restriction, respectively. These papers have generated considerable debate in the aging community.

Author(s): 
Cox, Lynne S.
Mattison, Julie A.
Publication Title: 
Rejuvenation Research

Can we extend human lifespan? Do we need to regulate lifestyle choices or can we simply pop a pill to make us live longer? These are questions raised by two new studies demonstrating significant lifespan extension in mice fed the drug rapamycin in their diet and in calorically restricted rhesus monkeys.

Author(s): 
Cox, Lynne S.
Publication Title: 
Journal of Cardiovascular Pharmacology

Constitutive autophagy is important for the control of the quality of proteins and organelles to maintain cell function. Damaged proteins and organelles accumulate in aged organs. The level of autophagic activity decreases with aging. Autophagic activity is regulated by many factors, such as the insulin receptor-signaling pathway, the TOR pathway, Sirt1, and caloric restriction. Autophagy-related genes are known to be essential for the lifespan extension of flies, nematodes, and mice.

Author(s): 
Yamaguchi, Osamu
Otsu, Kinya
Publication Title: 
Experimental Gerontology

The extension of both median and maximum lifespan and the suppression of age-related diseases in laboratory animals by reduced food intake, i.e., calorie restriction (CR) are regarded as hallmarks of CR's anti-aging action. The diverse efficacy of CR to counteract aging effects and its experimental reproducibility has made it the gold standard of many aging intervention studies of recent years.

Author(s): 
Chung, K. W.
Kim, D. H.
Park, M. H.
Choi, Y. J.
Kim, N. D.
Lee, J.
Yu, B. P.
Chung, H. Y.
Publication Title: 
Open Biology

Multi-cellular organisms need to successfully link cell growth and metabolism to environmental cues during development. Insulin receptor-target of rapamycin (InR-TOR) signalling is a highly conserved pathway that mediates this link. Herein, we describe poly, an essential gene in Drosophila that mediates InR-TOR signalling. Loss of poly results in lethality at the third instar larval stage, but only after a stage of extreme larval longevity.

Author(s): 
Bolukbasi, Ekin
Vass, Sharron
Cobbe, Neville
Nelson, Bryce
Simossis, Victor
Dunbar, Donald R.
Heck, Margarete M. S.
Publication Title: 
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

PURPOSE: To assess the efficacy of rapamycin treatment in chemoprevention and chemotherapy of tumorigenesis in a genetically defined mouse model of head and neck squamous cell carcinoma (HNSCC). Experimental design: Knockdown of Tgfbr1 and/or Pten using siRNA-mediated RNA interference was carried out in human HNSCC cell lines to analyze molecular changes in the mTOR pathway. Tgfbr1(flox/flox); Pten(flox/flox); K14-CreER(tam) mice were treated with oral gavage of tamoxifen for the conditional deletion of Tgfbr1 and Pten in oral mucosa, resulting in HNSCC.

Author(s): 
Sun, Zhi-Jun
Zhang, Lu
Hall, Bradford
Bian, Yansong
Gutkind, J. Silvio
Kulkarni, Ashok B.
Publication Title: 
Gerontology

The fungicide rapamycin increases lifespan in eukaryotes by interfering with the activity of a serine/threonine kinase called TOR (target of rapamycin). TOR complex 1 (TORC1) is an essential integrator of cellular nutrient cues, growth signals and cellular metabolism. Here, we review major components of TORC1, its downstream effectors and lifespan studies in various organisms involving these signaling components. In particular, we focus on the role of rapamycin in mitochondrial biogenesis, in metabolic regulation and in the control of reactive oxygen species production.

Author(s): 
Pan, Yong
Nishida, Yuya
Wang, Margaret
Verdin, Eric
Publication Title: 
Aging Cell

Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological tau is hyperphosphorylated and aggregates to form neurofibrillary tangles. The molecular mechanisms leading to tau accumulation remain unclear and more needs to be done to elucidate them. Age is a major risk factor for all tauopathies, suggesting that molecular changes contributing to the aging process may facilitate tau accumulation and represent common mechanisms across different tauopathies.

Author(s): 
Caccamo, Antonella
MagrÏ, Andrea
Medina, David X.
Wisely, Elena V.
LÛpez-Aranda, Manuel F.
Silva, Alcino J.
Oddo, Salvatore
Publication Title: 
The Journal of Clinical Investigation

Aging is like the weather: everyone talks about it, but no one seems to do anything about it. We believe this may soon change, as an improved understanding of the molecular and genetic pathways underlying aging suggests it is possible to therapeutically target the aging process and increase health span. This Review series focuses on fundamental cellular mechanisms of aging and their relationship to human disease.

Author(s): 
Newgard, Christopher B.
Sharpless, Norman E.
Publication Title: 
The Journal of Clinical Investigation

Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans.

Author(s): 
Lamming, Dudley W.
Ye, Lan
Sabatini, David M.
Baur, Joseph A.

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