Pharmacological interventions in the aging process
Review of research articles published in 2009 that have made or will make a significant contribution to the study of aging – Part 5.
The ultimate goal of biomedical research is the development of therapeutic drugs. As shown earlier, activation of mTOR (mammalian rapamycin target) is a necessary condition for human cells with the inactivated p21 gene to acquire a physiological aging phenotype, whereas inactivation of mTOR transfers cells from a state of physiological aging to a state of rest. In 2009, it was shown that the mTOR inhibitor, rapamycin, slows down the process of physiological aging of human and mouse cells with the inactivated p21 gene [11]. Similarly, inhibitors PI-3K and MEK, as well as LY-294002 and U0126 inactivated mTOR and suppressed physiological aging, transferring it to a resting state [38], which allows us to consider mTOR inhibitors of direct and indirect action as suppressors of aging.
The most impressive event of the year was the demonstration that taking rapamycin in middle-aged mice (600 days) significantly increased their life expectancy [39]. This effect was observed in three independent research centers using genetically heterogeneous mice selected to exclude the influence of genotype on predisposition to diseases [39]. Rapamycin also increased the lifespan of old mice at the age of 22 months [40]. Publications by Bjedov et al (Cell Metab, January 2010) and Moskalyov and Shaposhnikov (Rejuvenation Res, April-June 2010) will be analyzed next year.
Clioquinol metallochelate has been demonstrated to have a positive effect on a number of models of neurodegenerative diseases and inhibits the activity of the mitochondrial enzyme CLK-1 in mammalian cells. Nematodes and mice treated with clioquinol demonstrated a spectrum of phenotypes caused by a mutational decrease in CLK-1 activity. Considering that CLK-1 slows down the aging of these organisms, the results obtained indicate the ability of clioquinol (by inhibiting CLK-1) to slow down the aging process [41].
And finally, as a continuation of the work on the aging-slowing effects of the antioxidant SkQ1 targeting mitochondria [42], it was demonstrated that the "Skulachev ion" inhibits thymus involution in normal and predisposed to physiological aging rats [43].
Continuation: Stem cells and aging.
Portal "Eternal youth" http://vechnayamolodost.ru28.09.2011