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Pharmacology, genomics, and the evolutionary biology of ageing
Michael R Rose1, Laurence D Mueller, Anthony D Long
1Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697-2525, USA. mrrose@uci.edu
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.
Insights
Developing anti-aging medicine requires a strategic approach. This study proposes using genetically enhanced model organisms to identify biochemical pathways for increasing lifespan, paving the way for future human therapies.
Area of Science:
- Gerontology
- Genetics
- Biochemistry
Background:
- Aging is a complex biological process influenced by numerous genes and biochemical pathways.
- The failure to identify simple central controls for aging highlights the genomic complexity of the aging pathology.
- This complexity presents a significant challenge for developing effective anti-aging therapies.
Purpose of the Study:
- To propose a strategic approach for developing anti-aging therapies.
- To address the challenge of treating a genomically complex aging pathology.
- To outline a research and development (R&D) strategy for anti-aging medicine.
Main Methods:
- Utilize model systems that permit significant genetic intervention.
- Begin research with selected genetic lines exhibiting enhanced lifespan.
- Employ genomic methods to identify biochemical pathways associated with increased lifespan.
- Translate findings from model systems to rodent studies and eventually human clinical trials.
Main Results:
- The proposed strategy focuses on identifying specific biochemical pathways through genetic manipulation in model organisms.
- This approach aims to systematically uncover targets for anti-aging interventions.
- It emphasizes a phased R&D process, starting with foundational research in model systems.
Conclusions:
- A phased R&D strategy, starting with model systems, is essential for tackling the complexity of aging.
- Genomic identification of lifespan-increasing pathways in enhanced model organisms provides a viable route for pharmaceutical development.
- This methodical approach is more likely to succeed than initiating research directly with human populations or un-pre-screened compounds.