Applying More Rigor to the Search for Drug Candidates to Modestly Slow Aging

The majority of researchers interested in treating aging as a medical condition are involved in work that will, at best, only modestly slow the progression of age-related disease and dysfunction. They do not follow the SENS view of damage repair to produce rejuvenation, but rather the idea that one must alter the operation of metabolism in order to slow down the pace at which damage occurs. The scope of the possible benefits is much smaller via this approach, and further it is probably more expensive to achieve those lesser results. Altering metabolism safely requires a greater level of understanding than repairing the existing and well-understood forms of damage that produce aging, and generating that understanding is slow and expensive. You might look back at the past decade of work on sirtuins, for example, one tiny slice of the biochemistry associated with calorie restriction: a very large amount of time and money has gone into improving knowledge of that area of metabolism, but there is nothing of practical use to show for it as a result. Some research groups respond to this history with efforts to improve the process of drug development, to move towards more cost-effective ways to both analyze the vast mountains of existing data on metabolism and identify drug candidates that will produce the desired modest slowing of the aging process. Here is an example of the type:

Researchers have developed the GeroScope algorithm to identify geroprotectors - substances that extend healthy life. Hundreds of compounds were screened for geroprotective activity using computer simulations, and laboratory experiments were conducted on the ten substances that were identified using this algorithm. Decades of hard work by highly-competent research teams and millions of dollars are spent on the process of developing new drugs. And the screening and development process of geroprotectors, interventions intended to combat aging, a complex multifactorial biological process affecting every cell in the human body, is even more tedious. Computer modeling techniques may significantly reduce the time and cost of development. "The aging of the population is a global problem. Developing effective approaches for creating geroprotectors and validating them for use in the human body is one of the most important challenges for biomedicine. We have proposed a possible approach that brings us one step closer to solving this problem."

For several years the group studied cancer-related processes and relied on the Oncofinder, an algorithm designed to study and analyze the activation values of molecular pathways by comparing gene expression in cancerous and normal healthy cells, and also comparing tissue samples of different patients. The researchers applied a similar approach to develop GeroScope, which is able to compare changes in the cells of young and old patients and search for drugs with minimal side effects that compensate for these changes. To do this, the scientists analyzed transcriptomic data in "young" (donors aged between 15 and 30 years) and "old" (donors over the age of 60) samples from many human tissue types. This data was used for advanced computer modeling to identify and re-construct the molecular pathways associated with aging. Molecular pathways are a sequence of reactions that lead to changes in a cell. The most common molecular pathways are involved in metabolism and signal transduction. GeroScope modeled molecular pathways and analyzed cell reactions to various substances. Having chosen 70 compounds from the database of geroprotective drugs, the scientists used the new algorithm to identify 10 substances that could have geroprotector properties in accordance with the model.

The predictions made by the computer model were confirmed in cell cultures of human fibroblasts for several substances. Some of these drugs are already actively sold as dietary supplements individually. Further analysis of the pathway-level effects of many of these compounds provided insights into the possible combinations providing maximal cumulative effects and minimizing the possible adverse effects. "For computer modeling this is a very good result. In the pharmaceutical industry, 92% of drugs that are tested on animals fail during clinical trials in humans. The ability to simulate biological effects with such a high level of accuracy in silico is a real breakthrough. We hope that some of these drugs will soon be tested on people using biologically-relevant biomarkers of aging."

Link: https://mipt.ru/english/news/geroscope_a_computer_method_to_beat_aging

Comments

Low hanging fruit is still better than nothing. Same reason I take a number of well researched supplements and practice a longevity lifestyle because I want to be alive for LEV.

Posted by: Steve Hill at December 9th, 2016 3:20 PM
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