The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 18, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/gln067
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This article appears in the following The Journals of Gerontology Series A: Biological Sciences and Medical Sciences issue: Special Issue: Biology of Aging Summit [View the issue table of contents]
Can We Develop Genetically Tractable Models to Assess Healthspan (Rather Than Life Span) in Animal Models?
Division of Biology and Medicine, Brown University, Providence, Rhode Island
Address correspondence to Marc Tatar, PhD, Division of Biology and Medicine, Box G-W, Brown University, Providence, RI 02912. Email: marc_tatar{at}Brown.edu
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Abstract |
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Understanding healthspan is arguably the most relevant clinical, social, and economic feature of aging research. The model systems of worm, fly, and mouse are potentially powerful tools to achieve this aim. These models provide two unique approaches. The first is based on genetic screening for gain or loss of function mutations that ameliorate senescence. Genetic factors discovered by this process permit us to recognize causal and regulatory mechanisms of aging. A related screen looks for compounds that slow aging or act upon proteins that were initially identified from genetic analysis. The second research strategy uses manipulations of targeted genetic factors to test causal explanations for aging. These studies include transgenic organisms and genetic epistasis analysis. Overall, genetically driven research with model organisms is largely responsible for the breakthrough of aging biology in the past 15 years. Aging in these contexts, however, has been measured almost exclusively from cohort survival statistics such as life expectancy and age-specific mortality. This is for a good reason. Manipulated factors that extend life span are thought to unambiguously slow senescence and thus to reflect underlying causes of the aging process. But this approach is also common for a practical reason—healthspan is a poorly defined commodity in humans, let alone for genetic animal model systems. It was the consensus of the working session that making healthspan an operational metric would be an innovation needed for the genetic power of model systems to address this aspect of human aging.
Keywords Functional senescence; Healthspan; Drosophila; C. elegans.
Received: December 9, 2008; Accepted: December 9, 2008