New Scholar Award in Aging
Brad A. Rikke, Ph.D.
University of Colorado - Boulder

QTLs Specifying the Retardation of Reproductive Senescence by Dietary Restriction

Dietary restriction (DR, also referred to as calorie restriction, food restriction, and energy restriction) is the best-studied method of retarding senescence and mortality in mammals extending life span by as much as 50% in rodents. Understanding the molecular mechanism by which DR extends life span would thus contribute significantly to understanding the basic biology of aging and developing interventions that produce similar benefits.

Evolutionary theories have suggested that DR-induced life extension is pleiotropic to the retardation of reproductive senescence. Consequently, extended female fertility in response to DR could be a biomarker of DR-induced life extension. Moreover, genes specifying the extension of female fertility could underlie the molecular mechanism of DR-induced life extension. To identify such genes, we propose to map quantitative trait loci (QTLs) underlying the extension of female fertility by DR in the LSXSS and LXS recombinant inbred strains. A QTL is any one of a number of genetic regions specifying a quantitatively-measured trait. QTL mapping is designed for the express purpose of mapping on a continuous spectrum of phenotypic classes and thus is ideally suited for mapping on fertility extension.

Based on substantial preliminary results, we have determined that the LSXSS and LXS strains exhibit marked and heritable variation in a variety of responses to DR, including changes in body temperature, body weight, hair growth, and the extension of female fertility. The LXS series is the largest panel of recombinant inbred strains ever constructed (80 strains), which will allow for statistically significant and high resolution mapping of QTLs. We will also test whether the QTLs appear to specify multiple responses to DR. Because recombinant inbred strains are genetically stable, the QTL database will also allow for comparisons with any other responses to DR that are mapped in the future

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