Rapamycin

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Rapamycin -

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References:

Easter Island Drug Raises Cognition Throughout Life Span in Mice
ScienceDaily (June 29, 2012)
Rapamycin is an antifungal agent administered to transplant patients to prevent organ rejection.
http://www.sciencedaily.com/releases/2012/06/120629211902.htm

“…a serine/threonine kinase and component of the mTORC1 signaling complex, acts as an energy, nutrient, growth factor, stress, and redox sensor to increase protein synthesis and decrease macroautophagy…”

“…rapamycin extends life span in old mice, likely by a combination of increased autophagy and decreased mRNA translation…”

“…The use of safer, but perhaps weaker, indirect mTORC1 inhibitors, such as metformin and resveratrol…”

Rapamycin as an antiaging therapeutic?: targeting mammalian target of rapamycin to treat Hutchinson-Gilford progeria and neurodegenerative diseases.
Mendelsohn AR, Larrick JW.
Rejuvenation Res. 2011 Aug;14(4):437-41.
Source: Panorama Research Institute and Regenerative Sciences Institute, 1230 Bordeaux Drive, Sunnyvale, CA 94089, USA. amend@regensci.org
Abstract
Mammalian target of rapamycin (mTOR), a serine/threonine kinase and component of the mTORC1 signaling complex, acts as an energy, nutrient, growth factor, stress, and redox sensor to increase protein synthesis and decrease macroautophagy. mTORC1 plays a central role in the maintenance of homeostasis and its deterioration, seen in aging. The Food and Drug Administration (FDA)-approved immunosuppressive macrolide rapamycin binds immunophilin FKBP12 (FK506-binding protein) to inhibit mTORC1. Unlike most other interventions tested to date, inhibition of mTORC1 by rapamycin extends life span in old mice, likely by a combination of increased autophagy and decreased mRNA translation. Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder affecting children that is characterized by symptoms of premature aging, such as atherosclerosis. Increased autophagy induced by rapamycin reduces accumulation of progerin, an alternate spliced form of lamin A/C, that forms insoluble toxic aggregates, resulting in reduced HGPS-associated nuclear blebbing, growth inhibition, epigenetic dysregulation, and genomic instability. Rapamycin-induced autophagy also suppresses symptoms in mouse models of Alzheimer, Parkinson, and Huntington diseases, where toxic insoluble protein aggregates accumulate. On the basis of these results, modulation of mTORC1 function is a promising target for the development of therapeutics for neurodegenerative diseases and HGPS. Rapamycin is the obvious candidate for near-term evaluation in the treatment of these diseases. However, the substantial set of rapamycin-associated adverse effects, as well as the lack of aging-specific human data, should caution the routine use of rapamycin as an antiaging agent. The use of safer, but perhaps weaker, indirect mTORC1 inhibitors, such as metformin and resveratrol, may prove useful. Further study will ascertain whether such compounds extend human health or life span.
PMID: 21851176 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed?term=alzheimer%20metformin%20resveratrol

Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging.
Mouchiroud L, Molin L, Dallière N, Solari F.
Biofactors. 2010 Sep;36(5):377-82.
Source: UMR, CNRS Université Lyon, Centre Léon Bérard, France.
Abstract
Life expectancy at the turn of the 20th century was 46 years on average worldwide and it is around 65 years today. The correlative increase in age-associated diseases incidence has a profound public health impact and is an important matter of concern for our societies. Aging is a complex, heterogeneous, and multifactorial phenomenon, which is the consequence of multiple interactions between genes and environment. In this review, we survey animals models that have been of great help for both investigating mechanism of aging and identifying molecules, which slow down the onset of age-related diseases. Resveratrol (RSV) is one of those. We will report evidences supporting RSV as a molecule that acts by mimicking the beneficial effects of dietary restriction, and may share common downstream targets with rapamycin and metformin. Although those molecules do not reveal all the secrets of the fountain of youth, they may help us maintaining the quality of life in the old age.
PMID: 20848587 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/2084858

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