Rules for the use of model organisms in anti-aging pharmacology.
The use of animal models for initially screening anti-aging drugs is a promising approach for drug discovery. However, there a number of potential artifacts, confounds and errors that can arise in such research programs. The following rules are intended to minimize such problems: (1) since aging occupies an increasing proportion of human adulthood, data that conflate aging and late life should not be extrapolated to human aging; (2) the response to candidate medications should show a normal dose-response pattern, although not necessarily a linear response; (3) medicated animal models should not be hypometabolic; (4) medicated animal models should not show pronounced reductions in fertility; (5) medicated animal models should not exhibit general nervous system depression; (6) the effect of the medication should not be highly sensitive to the culture environment; (7) the effect of the medication should not be highly dependent on the genetic ancestry of the stock employed, leaving aside inbreeding, which should be avoided because humans are not generally inbred. While these rules do not guarantee successful extrapolation of successful drug results from the animal model to humans in a clinical setting, the failure to adhere to these rules should raise doubts about such extrapolation.
Jafari
Mahtab
M
Pharmaceutical Sciences Program, University of California, Irvine, CA 92697, USA. mjafari@uci.edu
Rose
Michael R
MR
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005298:Fertility / Q000187:drug effects; D017408:Guidelines as Topic; D040941:Heredity; D023421:Models, Animal; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology; D010601:Pharmacology, Clinical / Q000379:methods* / Q000592:standards; D012107:Research Design; D015996:Survival Rate