How to get past the target of rapamycin?
Researchers at the Joslin Diabetes Research Center, working under the guidance of Professor Keith Blackwell, have identified the key mechanism of action of TOR protein kinase (target of rapamycin), which is a critical regulator of cell growth, playing an important role in the aging process and the development of a number of diseases. This discovery not only sheds light on the physiology of aging, but may also lead to the emergence of new methods for increasing life expectancy and treating age-related diseases such as cancer, type 2 diabetes and neurodegeneration.
Over the past decade, the results of several studies have demonstrated that inhibiting the activity of TOR, which stimulates cell growth by regulating protein synthesis, increases the life expectancy of representatives of various species, including fruit flies and mice. Subsequent studies are devoted to a detailed explanation of the mechanisms underlying this effect.
The activity of TOR, which is necessary for the development of the body in the early stages of life and can cause age-related deterioration of the body in its later stages, is involved in the pathogenesis of a number of chronic diseases, including diabetes, diseases of the cardiovascular system, cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In diabetes, TOR activity has a twofold effect.
In their latest work, the authors found that TOR has a direct effect on two important regulatory proteins: SKN-1 and DAF-16. These proteins control the activity of genes that protect the body from metabolic and proteotoxic stress (the result of accumulation and aggregation of non-folded proteins in the cell), as well as from stress caused by environmental factors.
TOR protein kinase is involved in the work of two signaling mechanisms mediated by the TORC1 and TORC2 molecular complexes. It turned out that the suppression of the activity of TOR (in particular the TOR1 complex) by genetic intervention, as well as by using the famous red wine ingredient resveratrol, which is a natural inhibitor of TOR, mobilizes SKN-1 and DAF-16, which leads to the activation of protective genes, thereby increasing resistance to stress and increasing life expectancy. These data were obtained in experiments on C.elegans roundworms, but activation of protective genes is also observed in mice. However, according to the authors, inhibition of TOR kinase can have serious undesirable side effects, since this enzyme plays an important role in the basic physiological processes of cell growth and division. Therefore, it is advisable to search for ways to selectively affect the signaling mechanism mediated by complex 1, or directly on the SKN-1 or DAF-16 genes, completely bypassing the TOR inhibition stage.
Article by Stacey Robida-Stubbs et al. TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO is published in the journal Cell Metabolism.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
Important Mechanism That Affects the Aging Process Identified.
02.05.2012