title: Pharmacology, genomics, and the evolutionary biology of ageing.
abstract: Aging is a multifold process affected by many genes and thus many biochemical pathways. This conclusion is underscored by the failure to find simple central controls for the aging process during the 20th Century. This situation poses a fundamental challenge to anti-aging medicine: how to develop effective therapies for a genomically complex pathology. We propose such a strategy. As a first step, we recommend the use of model systems in which significant genetic intervention is not proscribed or impractical. Second, we propose that work with such model systems begin with selected lines that have genetic enhancements that allow increased lifespan. Third, genomic methods should be used to identify a number of biochemical pathways for increasing lifespan. Fourth, biochemical pathways that have been identified in model systems would then be available for pharmaceutical development, first in rodents, eventually in a clinical human population. This may seem to be a cumbersome R&D strategy, but starting with human populations or inadequately pre-screened compounds would be unlikely to succeed because of the complexity of the aging problem.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697-2525, USA. mrrose@uci.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rose
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Mueller
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Long
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D017173:Caenorhabditis elegans; D004330:Drosophila; D016678:Genome; D006801:Humans; D009154:Mutation