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Anti-Aging Drug Discovery in Experimental Gerontological Studies
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Alexander N. Khokhlov, Alexander A. Klebanov, Galina V. Morgunova
In our opinion, the use of the stationary phase aging model in many cases makes it possible to avoid many of these problems, because the key factor that triggers the “aging” of all cells used in experiments is the restriction of cell proliferation with the help of various quite physiological impacts. A classic example is the chronological aging of yeast (Breitenbach et al. 2012; Khokhlov 2016), the results of studies of which are often pretty successfully used for studying the mechanisms of aging of humans and animals. In particular, experiments with the yeast S. cerevisiae showed that rapamycin, a well-known TOR inhibitor, in small doses that are sufficient for slowing down the proliferation of yeast cells but do not completely block this process, increases the culture life span in the chronological aging model (Powers et al. 2006; Alvers et al. 2009). Later, this compound was shown to extend the life span of experimental animals—mice (Harrison et al. 2009; Miller et al. 2014) and fruit flies (Bjedov et al. 2010). It should be noted that, according to the ideas of some researchers (Alvers et al. 2009; Rubinsztein et al. 2011; Morgunova et al. 2016b), the positive “gerontological” effect of rapamycin may be associated with the activation of autophagy. It also cannot be ruled out that the beneficial effect of rapamycin on the life span of animals may be due to its ability to suppress the emergence and development of malignant tumors (Blagosklonny 2006; Neff et al. 2013). As already mentioned above, in this case, it can hardly be considered a geroprotector. In addition, it is interesting to note that animals may develop tolerance to rapamycin over time. For this reason, some authors suggest that this drug should be used in combination with other active compounds, such as resveratrol (Alayev et al. 2015). Unfortunately, such problems are unlikely to be “caught” in cytogerontological studies.
Is anti-ageing drug discovery becoming a reality?
Published in Expert Opinion on Drug Discovery, 2020
Life extension in experiments with wild type animal models. Theoretically, based on the meaning of the term, the geroprotector should prolong the life of the model beyond the intact species’ maximum lifespan, protecting it from one or more mechanism of aging. However, in practice, at best, we are talking about increasing the lifespan by tens of percent. Therefore, it is more accurate to talk about gerosuppressors, and not geroprotectors.Improvement of molecular, cellular, and physiological biomarkers to a younger state or slow down the progression of age-related changes in human.Most potential geroprotectors are preventive only when applied at relatively high concentrations. The lifespan-extending dose should be several orders of magnitude less than the toxic dose.Minimal side effects at the therapeutic dosage at chronical application.The potential benefit of taking the geroprotector may come after a long period of time. Potential geroprotectors should initially improve some parameters of health-related quality of life: physical, mental, emotional, or social functioning of the person. This can serve as the basis for their chronical use.